Spinal cord stimulator

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Spinal cord stimulator

Spinal cord stimulator

Spinal cord stimulator is an implanted spinal cord stimulation device that sends low levels of electricity directly into your spinal cord to relieve pain. Spinal cord stimulator consists of thin wires (the electrodes) and a small, pacemaker-like battery pack (the generator). The electrodes are placed between your spinal cord and the vertebrae (the epidural space), and the generator is placed under your skin, usually near your buttocks or abdomen. Spinal cord stimulation is used most often after nonsurgical pain treatment options have failed to provide sufficient relief. Spinal cord stimulators require two procedures to test and implant the device: the trial and the implantation.

Spinal cord stimulator is a long-lasting procedure to treat nerve pain problems. A device is implanted into the spine, and a remote control is used to send low levels of electricity. It causes tingling against the nerves in the back or neck, which reduces the amount of pain felt.

The procedure is done in two steps, with the first step as a trial to see if it provides relief. If pain relief is above 60%, the second step is to permanently implant the device.

Experts still don’t fully understand the mechanisms behind spinal cord stimulation, but they know that spinal cord stimulator may target multiple muscle groups directly from the spine and even alter how the brain senses pain.

Traditional spinal cord stimulators replace the sensation of pain with light tingling, called paresthesia. For patients who find these paresthesiae uncomfortable, newer devices offer “sub-perception” stimulation that cannot be felt.

Many of the latest devices are placed by physicians with highly specialized training in interventional pain management under X-ray and/or ultrasound guidance.

Spinal cord stimulation results in inadequate pain relief in about 50% of patients ¹. Tolerance can also occur in up to 20 to 40 percent of patients. The effectiveness of the spinal cord stimulation decreases over time ².

Spinal cord stimulator types

Spinal cord stimulators come in 3 main types:

Conventional implantable pulse generator (IPG) is a battery-operated spinal code stimulator. A battery is placed in the spine during an operation. When it runs out, the battery must be replaced with another surgery. This device can be a good choice for people with pain in just one body part because it has a lower electrical output.
Rechargeable implantable pulse generator (IPG) works similarly to the conventional spinal code stimulator, with the difference that the battery can be recharged without another surgery. Because the energy source is rechargeable, these spinal code stimulators can put out more electricity. This may be a better choice for people with pain in the lower back or in one or both legs, as the electrical signal can reach further.
Radiofrequency stimulator uses a battery that’s outside the body. Radiofrequency stimulator is rarely used today because of newer designs and better technology. It has rechargeable batteries, and like the rechargeable implantable pulse generator (IPG), it may be better for people with pain in the lower back and legs because of the device’s power.

Your surgeon will explain how to operate the device and adjust the intensity of the electrical signal, which all three types of stimulators support. Different body positions may require different stimulator settings, such as one setting that works better for sitting and another for walking. To help you easily access the most used settings, most devices allow doctors to save two or three preset programs. Some newer devices feature several waveforms for electricity delivery, including high frequency, burst and high-density stimulation.

What is spinal cord stimulation used for?

Spinal cord stimulation is used most often after nonsurgical pain treatment options have failed to provide sufficient relief. Spinal cord stimulators may be used to treat or manage different types of chronic pain, including:

Back pain, especially back pain that continues even after surgery (failed back surgery syndrome)
Post-surgical pain
Arachnoiditis (painful inflammation of the arachnoid, a thin membrane that covers the brain and spinal cord)
Heart pain (angina) untreatable by other means
Injuries to the spinal cord
Nerve-related pain (such as severe diabetic neuropathy and cancer-related neuropathy from radiation, surgery or chemotherapy)
Peripheral vascular disease
Complex regional pain syndrome
Pain after an amputation
Visceral abdominal pain and perineal pain

Spinal cord stimulation can improve overall quality of life and sleep, and reduce the need for pain medicines. It is typically used along with other pain management treatments, including medications, exercise, physical therapy and relaxation methods.

Who should get a spinal cord stimulator?

As with all treatments, your doctor will want to make sure spinal cord stimulation is right for you and that it is likely to provide significant relief from your chronic pain. To make this recommendation, your pain specialist will likely order imaging tests and psychological screening. Some insurance companies require psychological screening to ensure disorders like depression or anxiety aren’t worsening your pain.

Each patient is different, but generally, people who benefit the most from spinal cord stimulation are those who:

Have not experienced sufficient pain relief with medications, less-invasive therapies or prior surgeries
Do not have psychiatric disorders that would decrease the effectiveness of the procedure

Why Spinal cord stimulation Procedure is Performed?

Your doctor may recommend spinal cord stimulation if you have:

Back pain that continues or gets worse, even after surgery to correct it
Complex regional pain syndrome (CRPS)
Long-term (chronic) back pain, with or without arm or leg pain
Nerve pain or numbness in the arms or legs
Swelling (inflammation) of the lining of the brain and spinal cord

Spinal cord stimulator is used after you have tried other treatments such as medicines and exercise and they have not worked.

The main components include an implanted signal generator that is connected to one or two implanted leads, and externally worn transmitter that is doctor and patient controlled. The therapy utilizes pulsed electrical current to create an energy field that acts on nerves near the spinal column to block nerve impulses in the spine ³.

Stimulator placement is done in two stages. A trial (test) stage is done to see how well spinal cord stimulation works for you. If the trial stage is a success, the permanent stimulator system is put into place.

Spinal cord stimulator contraindications

Pacemakers and defibrillators are often compatible with spinal cord stimulator implants ⁴. However, a history of a previous cardiac pacemaker or cardiac defibrillator requires the approval of spinal cord stimulator implantation by a cardiologist before the procedure ⁴. Having either a cardiac pacemaker or defibrillator remains a relative contraindication to spinal cord stimulator implant. Both devices require close follow up following spinal cord stimulator implants ⁵, ⁶, ⁷. Severe low platelet count (thrombocytopenia) or uncontrolled bleeding disorder (coagulopathy) are also contraindications to spinal cord stimulator implant due to increased risk of a spinal epidural hematoma ⁴. Active infection is an absolute contraindication to implantation of a spinal cord stimulator ⁴. There is limited information regarding spinal cord stimulator implantation in a pregnant patient ⁸. Although, given the need for fluoroscopy to guide the spinal cord stimulator procedure, the procedure is almost always postponed until birth.

Spinal Cord Stimulator Surgery

Spinal cord stimulators require two procedures to test and implant the device: the trial and the implantation.

Spinal cord stimulator trial

The first step is a trial period. Your surgeon will implant a temporary device for you to test out. Your skin will be numbed with a local anesthetic. Guided by a specific type of X-ray called fluoroscopy, your surgeon will carefully insert the electrodes (wires) in the epidural space of your spine. The location of your pain affects where these electrodes will be placed along the spine. Your surgeon may ask for your feedback during the procedure to best position the electrodes. This trial procedure typically requires only one incision in your lower back to place the electrodes (wires). These electrodes (wires) will be connected to a small current generator/battery outside of your body that you carry like a cell phone typically on a belt, you’ll wear around your waist. The procedure takes about 1 hour. You will be able to go home after the leads are placed.

If the treatment greatly reduces your pain, you will be offered a permanent generator. The generator will be implanted a few weeks later.

You will be asleep and pain-free with general anesthesia.
The generator will be inserted under the skin of your abdomen or buttocks through a small surgical cut.
The procedure takes about 1 to 2 hours.

The generator runs on batteries. Some batteries are rechargeable. Others last 2 to 5 years. You will need another surgery to replace the battery.

For about a week, you will evaluate how well the device reduces your pain. The trial is considered a success if you experience a 50% or greater reduction in pain level.

If unsuccessful, the wires can easily be removed in the clinic without damage to the spinal cord or nerves. If successful, surgery is scheduled to permanently implant the device.

Spinal Cord Stimulator Implantation

During the permanent implantation procedure, the generator is placed underneath the skin and the trial electrodes are replaced with sterile electrodes. Unlike the trial electrodes, these will be anchored by sutures to minimize movement.

The implantation can take about 1-2 hours and is typically performed as an outpatient procedure.

After the local anesthesia has been administered, your surgeon will make one incision (typically along your lower abdomen or buttocks) to hold the generator and another incision (along your spine) to insert the permanent electrodes. The incisions are about the length of a driver’s license. As in the trial procedure, fluoroscopy is used to determine where the electrodes are placed.

Once the electrodes and generator are connected and running, your surgeon will close the incisions.

Your surgeon may provide sedation to keep you comfortable and ask for your feedback during placement of the electrodes.

After the Procedure

After the permanent generator is placed, the surgical cut will be closed and covered with a dressing. You will be taken to the recovery room to wake up from the anesthesia.

Most people can go home the same day, but your surgeon may want you to stay overnight in the hospital. You will be taught how to care for your surgical site.

You should avoid heavy lifting, bending, and twisting while you are healing. Light exercise such as walking can be helpful during recovery.

After the procedure you may have less back pain and will not need to take as much pain medicines. But, the treatment does not cure back pain or treat the source of the pain.

Spinal cord stimulator complications

Risks of this surgery include any of the following ³:

Cerebrospinal fluid (CSF) leakage
Damage to the nerves that come out of the spine, causing paralysis, weakness, or pain that does not go away
Infection of the battery or electrode site (if this occurs, the hardware usually needs to be removed)
Movement of or damage to the generator or leads that requires more surgery
Pain after surgery
Problems with how the stimulator works, such as sending too strong of a signal, stopping and starting, or sending a weak signal
The stimulator may not work

The spinal cord stimulator device may interfere with other devices, such as pacemakers and defibrillators. After the spinal cord stimulator is implanted, you may not be able to get an MRI anymore. Discuss this with your doctor.

Complication rates for spinal cord stimulators are high, ranging from 5% up to 40% ⁹, ¹⁰. Most commonly, lead migration occurs, causing inadequate pain relief and requiring revision surgery and anchoring ¹¹, ¹². Lead movement often occurs in the cervical region of the spinal cord, given an increased range of motion of the cervical vertebra ¹³, ¹⁴. Spinal cord stimulator lead fracture can occur in up to 9% of placements ¹⁵, ¹⁶. Seromas are also very common and may require surgical incision and drainage ⁹, ¹⁷. The risk of infection following a spinal cord stimulator placement is between 2.5% and 12% ¹⁸, ¹⁹. Direct spinal cord trauma could occur. The most significant infectious complication would be a spinal cord abscess. Dural puncture is rare but can cause a post-dural headache in up to 70% of patients ¹⁷, ²⁰, ²¹. The most critical adverse event in spinal cord stimulator placement would be a spinal epidural hematoma, which requires immediate neurosurgical decompression. The incidence of a spinal epidural hematoma is 0.71% ²².

What is Chronic Pain?

Chronic pain also called chronic pain syndrome (CPS) or persistent pain is an umbrella term referring to pain that lasts 3 to 6 months or pain that persists past “normal healing time” ²³, ²⁴, ²⁵, ²⁶, ²⁷, ²⁸, ²⁹, ³⁰, ²³, ³¹. The International Association for the Study of Pain (IASP) defines “chronic pain” as persistent or recurrent pain lasting longer than 3 months ²³, ²⁴. Unlike acute pain, which is temporary, chronic pain can be constant or come and go, often interfering with daily life and affecting your physical and emotional well-being ³². It can stem from an ongoing health condition or persist even after the initial cause has been treated or is no longer present.

Pain is an unpleasant physical feeling, such as a prick, tingle, sting, burn, or ache. Pain may be sharp or dull. You may feel pain in one area of your body, or all over.

There are two types of pain: acute pain and chronic pain ³³.

Acute pain happens suddenly, starts out sharp or intense, and serves as a warning sign of disease or threat to the body. Acute pain lets you know that you may be injured or a have problem you need to take care of. Acute pain is caused by injury, surgery, illness, trauma, or painful medical procedures and generally lasts from a few minutes to less than six months. Acute pain usually disappears whenever the underlying cause is treated or healed.
Chronic pain is different. Chronic pain usually doesn’t have a useful purpose. The pain may last for weeks, months, or even years. The original cause may have been an injury or infection. There may be an ongoing cause of pain, such as arthritis or cancer. In some cases there is no clear cause. Environmental and psychological factors can make chronic pain worse. Chronic pain can significantly affect a person’s ability to perform daily activities, work, mood and engage in social interactions. Chronic pain can also affect your sleep leading to exhaustion and psychological stress.
The transition from acute to chronic pain may be understood as a series of relatively discrete changes in your brain and spinal cord (central nervous system) ³⁴, ³⁵, ³⁶, ³⁷, ³⁸, ²⁸. Chronic pain involves the activation of secondary mechanisms such as the sensitization of second-order neurons by upregulation of N-methyl-D-aspartic acid (NMDA) channels and alteration in microglia cytoarchitecture. Chronic pain, with its multiple factors for perpetuation, often benefits from a multidisciplinary approach to treatment ³⁹.
Acute pain and chronic pain need to be treated differently. Acute pain can often be relieved with painkillers such as acetylsalicylic acid (Aspirin), ibuprofen and paracetamol (acetaminophen). But these drugs don’t work in many people who have chronic pain. Even strong painkillers such as opioids often don’t help chronic pain.

Pain is also personal and subjective, and individuals may perceive and describe it differently, meaning what’s painful for one person may not be painful for another person. The experience of chronic pain is highly individual, with different people experiencing varying levels of intensity and impact. This variation makes personalized treatment plans essential for effective management.

Pain research has led to some discoveries that might be surprising ³³:

The fear of pain can be painful. Even if your body isn’t in any real danger and your tissue and organs are healthy, you may still feel pain – if your brain thinks you’re in danger. The purpose of this kind of pain is to help you avoid the thing that is thought to be dangerous. One aim of modern pain management is to reduce the fear of pain – for example, the fear of pain caused by exercising too much or doing the wrong kind of exercise.
Pain that has no physical cause is still “real”. People who have pain for no known physical reason are sometimes accused of imagining it. That’s not true, though. Their pain just arises in a different way. A scientific experiment made this clearer: healthy participants agreed to wear a cap that sends out electrical impulses that cause headaches or so they were told. In actual fact, the cap didn’t send out any impulses or have any other effects. But the people in the experiment still felt pain and the higher the “pain impulse” dial was turned up, the worse their pain became. The participants didn’t imagine the pain, though. They really felt it. This is because their brains thought they were being exposed to danger, so it produced pain signals.
The severity of pain often isn’t directly related to the extent of physical damage. Very severe injuries like gunshot wounds don’t always cause immediate pain. Severe pain would make it harder for the wounded person to get out of danger in order to survive. Another example, some people have severe damage to their spine caused by wear and tear but it doesn’t hurt and some people have really bad back pain although no damage can be seen on x-ray images.
Pain depends on outside factors. Pain severity can be influenced by how dangerous your brain considers something to be. This can be shown by the following experiment: A group of people volunteered to have a very cold metal pin (minus 20 degrees Celsius, which is about minus 4 degrees Fahrenheit) held against their hand for half a second. The metal pin either had a red light or a blue light on it. People who saw a red light felt more severe pain than people who saw a blue light – even though the temperature of the metal pin was the same, and it was held against their hand for the same amount of time. This is because we tend to associate the color red with danger and extreme heat, and see it as a more threatening color.
Pain is influenced by how you feel. For instance, people feel less pain if their doctor takes more time for them and explains what is causing the pain. And pain may feel worse on a stressful day at work than at a weekend when out and about with good friends. Last, but not least, positive thoughts, pleasant experiences or music can distract you from pain or even allow you to forget it for a while.

These things are important for people who have chronic pain. They show us that your experience of pain can be influenced by what your brain associates with it. For instance, fear of pain plays an important role. Understanding what causes chronic pain may also help people to cope with it better.

Common chronic pain complaints include headache, low back pain, cancer pain, arthritis pain, neurogenic pain (pain resulting from damage to the peripheral nerves or to the central nervous system itself), psychogenic pain (pain not due to past disease or injury or any visible sign of damage inside or outside the nervous system). A person may have two or more co-existing chronic pain conditions. Such conditions can include chronic fatigue syndrome, endometriosis, fibromyalgia, inflammatory bowel disease, interstitial cystitis, temporomandibular joint dysfunction, and vulvodynia. It is not known whether these disorders share a common cause.

Depression and stress tend to make pain worse, including chronic pain.

Many older adults have chronic pain. Women also report having more chronic pain than men, and they are at a greater risk for many pain conditions. Some people have two or more chronic pain conditions.

Chronic pain can occur anywhere in the body. People with chronic pain complain of ⁴⁰:

headaches
back pain
cancer pain
arthritis pain
pain resulting from nerve damage.

The pain can be described as ⁴⁰:

a dull ache
soreness
stiffness
stinging
squeezing
throbbing
burning
shooting.

Sometimes people with chronic pain have other symptoms. These could include feeling tired, having trouble sleeping, or mood changes. The pain itself often leads to other symptoms. These include low self-esteem, anger, depression, anxiety, or frustration.

Chronic pain is not always curable, but treatments can help. They include ⁴¹:

Pain Relievers and other medicines
Acupuncture and massage
Electrical stimulation e.g. spinal cord stimulator, brain stimulation
Surgery
Physical therapy
Psychotherapy
Relaxation and meditation therapy
Biofeedback
Behavior modification
Some physicians use placebos, which in some cases has resulted in a lessening or elimination of pain.

Table 1. Chronic Pain Classification (11th version of the International Classification of Diseases (ICD-11))

Pain Type	Definition	Neurobiologic Mechanism	Examples
Chronic Primary Pain
1. Chronic widespread pain	Widespread pain persisting for longer than 3 months, associated with emotional distress or functional disability	Central sensitization	Fibromyalgia
2. Complex Regional Pain Syndrome (CRPS)	Disorder of body region, usually distal limbs, characterized by pain (allodynia), swelling, loss of function, vasomotor instability, skin changes	Neuropathic Central sensitization	Chronic Regional Pain Syndrome (formerly reflex sympathetic dystrophy)
3. Chronic primary headache or orofacial pain	Idiopathic headache or orofacial pain, not secondary to another condition	Nociceptive Neuropathic Central sensitization	Chronic migraine or temporomandibular disorder
4. Chronic primary visceral pain	Persistent or recurrent pain originating from internal organs, without a clear organic cause	Central sensitization	Irritable bowel syndrome
5. Chronic primary musculoskeletal pain	Chronic pain experienced in muscles, bones, joints, or tendons that cannot be attributed directly to a known disease or tissue damage process ⁴²	Nociceptive Neuropathic Central sensitization	Non-specific low back pain
Chronic Secondary Pain
1. Chronic cancer-related pain	Pain caused by the cancer itself (by the primary tumor or by metastases) or by its treatment (surgery, chemotherapy, or radiotherapy) ⁴³	Nociceptive Neuropathic Central sensitization	Chronic cancer pain, chronic cancer treatment pain (eg, chemotherapy-induced peripheral neuropathy, radiation fibrosis)
2. Chronic postsurgical or posttraumatic pain	Pain secondary to surgery or trauma which persists for longer than 3 months	Nociceptive Neuropathic Central sensitization	Incisional pain, nerve injury due to trauma or surgery (eg, persistent whiplash or low back pain after trauma)
3. Chronic neuropathic pain	Pain caused by a lesion or disease of the somatosensory nervous system ⁴⁴	Neuropathic	Trigeminal neuralgia, chronic painful polyneuropathy (eg, diabetic polyneuropathy), postherpetic neuralgia
4. Chronic secondary headache or orofacial pain	Headaches or orofacial pains, secondary to a medical condition	Nociceptive Neuropathic Central sensitization	Head/face pain secondary to trauma, tumor, hemorrhage, etc.
5. Chronic secondary visceral pain	Persistent or recurrent pain originating from internal organs, due to a secondary cause	Nociceptive	Abdominal pain due to adhesions or ischemia
6. Chronic secondary musculoskeletal pain	Persistent or recurrent pain that arises as part of a disease process directly affecting bones, joints, muscles, or related soft tissues	Nociceptive	Rheumatoid arthritis, osteoarthritis

[Source ²⁹ ]

Chronic pain causes

The cause of chronic pain is multifactorial and complex and still is poorly understood ⁴⁵, ⁴⁶, ⁴⁷, ²⁶. The development and chronicization of pain can be also influenced by several psychological and social factors, such as depression, catastrophizing, avoidance behaviors, somatization, responses from significant others and cultural attitudes ⁴⁸. In addition, chronic pain is often accompanied by several biological (eg, depression of the immune system), physical (eg, impaired functioning), psychological (eg, depression) and social consequences (eg, job loss), which all contribute in aggravating the patient’s burden ⁴⁹.

The most common causes of chronic pain include ³²:

Injuries
Arthritis
Back problems
Nerve damage
Fibromyalgia
Headaches and migraines
Post-surgical pain
Cancer
Infections
Stress
Anxiety and depression
Poor posture and overuse

Certain factors can contribute to an increased risk of chronic pain (female gender, older age, lower socioeconomic status, geographical and cultural background, and genetics ⁵⁰, ⁵¹. Other factors associated with chronic pain conditions are modifiable, such as smoking status, alcohol intake, nutrition, obesity, comorbidities, employment status and occupational factors, and physical activity level ⁵⁰, ⁵².

An observational study found that individuals tend to smoke more cigarettes when experiencing higher pain levels and make fewer attempts to quit smoking during such periods ⁵³. This behavior can be attributed to the acute pain-relieving effect of nicotine, which makes it challenging for them to quit due to the pleasurable sensations it provides ⁵⁴. Despite its short-term pain relief benefits, tobacco smoking is associated with chronic pain intensity and prevalence in the long run ⁵⁵, ⁵⁴, ⁵⁶, ⁵⁷. This highlights the importance of smoking cessation strategies to improve the individual’s understanding of the relationship between pain and smoking, potentially increasing their commitment to a smoking cessation program ⁵³.

Smoking status in individuals with chronic pain is also associated with alcohol-drug and opioid dependence ⁵⁸, ⁵⁹. When smoking and alcohol consumption are combined, their negative effects are compounded due to the alcohol’s ability to stop the body’s capacity to breakdown the cancer causing compounds found in cigarettes ⁶⁰. Furthermore, it is worth noting that alcohol initially has an acute pain relieving effect ⁶¹, ⁶², which can elevate the risk of alcohol abuse in individuals with chronic pain ⁶¹, ⁶³.

Recent studies have shown that chronic pain patients with high levels of pain catastrophizing are more likely to engage in heavy drinking ⁶⁴.

Some authors have suggested that chronic pain might be a learned behavioral that begins with a noxious stimulus that causes pain. This pain behavior then is rewarded externally or internally. Therefore, this pain behavior is reinforced, and then it occurs without any noxious stimulus. Internal reinforcers are relief from personal factors associated with many emotions (eg, guilt, fear of work, sex, responsibilities). External reinforcers include such factors as attention from family members and friends, socialization with the physician, medications, compensation, and time off from work.

Patients with several psychological syndromes (eg, major depression, somatization disorder, hypochondriasis, conversion disorder) are prone to developing chronic pain syndrome.

Various neuromuscular, reproductive, gastrointestinal (GI), and urologic disorders may cause or contribute to chronic pain. Sometimes multiple contributing factors may be present in a single patient.

In a study by Alonso-Blanco ⁶⁵, a connection was found in women between the number of active myofascial trigger points (MTrPs) and the intensity of spontaneous pain, as well as widespread mechanical hypersensitivity. Nociceptive inputs from these MTrPs may be linked to central sensitization.

A literature review by Gupta et al ⁶⁶ indicated that in chronic pain patients, primary sensorimotor structural and functional changes are more prominent in females than in males. Males and females differed with regard to the nature and degree of insula changes (with males showing greater insula reactivity), as well as in the extent of anterior cingulate structural changes and in reactivity to emotional arousal.

Chronic pain symptoms

Chronic pain is an umbrella term referring to pain that lasts 3 to 6 months or pain that persists past “normal healing time” ²³, ²⁴, ²⁵, ²⁶, ²⁷.

The most common symptoms of chronic pain include ³²:

Persistent pain
Fatigue
Stiffness
Sleep disturbances
Mood changes
Decreased mobility
Sensitivity to touch
Appetite changes
Cognitive difficulties
Social withdrawal

Common chronic pain syndrome include headache, low back pain, cancer pain, arthritis pain, neurogenic pain (pain resulting from damage to the peripheral nerves or to the central nervous system itself), psychogenic pain (pain not due to past disease or injury or any visible sign of damage inside or outside the nervous system). A person may have two or more co-existing chronic pain conditions, several of which cause pain, may occur together. Such conditions can include chronic fatigue syndrome, endometriosis, fibromyalgia, irritable bowel syndrome, inflammatory bowel disease, interstitial cystitis (painful bladder syndrome), temporomandibular joint dysfunction, and vulvodynia (chronic vulvar pain).

Chronic pain diagnosis

Diagnosing chronic pain typically involves a comprehensive evaluation to understand the underlying causes and assess the impact on the patient’s life. Your medical doctor will likely ask you about your symptoms, the intensity and location of pain, and the history of your injury, surgery, or illness. Young patients may be asked to rate their pain intensity using the faces of pain scale.

The decision to perform any laboratory or imaging evaluations is based on the need to confirm the diagnosis and to rule out other potentially life-threatening illnesses. Sometimes certain investigations are needed to provide appropriate and safe medical or surgical treatment. The recommended treatment should be based on clinical findings or changes in examination findings.

Extreme care should be taken during diagnostic testing for chronic pain syndrome. Carefully review prior testing to eliminate unnecessary repetition.

Routine complete blood count (CBC), urinalysis, and selected tests for suspected disease are important. Urine or blood toxicology is important for drug detoxification, as well as opioid therapy.

Some common diagnostic methods and tests include:

medical history review
physical examination
pain assessment tools
imaging studies
- x-rays
- MRI
- CT scans
- bone scans
- ultrasound
electromyography (EMG) and nerve conduction studies
blood tests
nerve blocks and injections
psychological evaluation

Imaging studies

Imaging studies, including with radiography, magnetic resonance imaging (MRI), and computed tomography (CT) scanning, are important tools in the workup of patients with chronic pain syndrome.

Chronic pain treatment

Management of chronic pain in patients with multiple problems is complex, and may require a comprehensive approach involving medical treatment, reducing/tapering or even stopping non-working medications, lifestyle changes, physical therapy, psychological treatment such as cognitive behavioral therapy (CBT) or mindfulness and sometimes alternative treatments like acupuncture and mind-body techniques ⁶⁷, ⁶⁸. Physical therapy techniques include hot or cold applications, positioning, stretching exercises, traction, massage, ultrasonographic therapy, transcutaneous electrical nerve stimulation (TENS), and manipulations. Lifestyle modifications, such as a healthy diet, weight management, and sleep hygiene, are also often recommended. Other treatments include nerve blocks, spinal cord stimulation, and intrathecal morphine pumps. The most effective treatment plans are often personalized, combining several of these approaches based on the individual’s specific condition, type of pain, and overall health. The goal is often to reduce pain and most commonly improve function rather than eliminate the pain entirely.

Treatment of chronic pain must be tailored for each individual patient. The treatment should be aimed at interruption of reinforcement of the pain behavior and modulation of the pain response. The goals of treatment must be realistic and should be focused on restoration of normal function (minimal disability), better quality of life, reduction of use of medication, and prevention of relapse of chronic symptoms.

Psychological interventions, in conjunction with medical intervention, physical therapy, and occupational therapy (OT), increase the effectiveness of the treatment program ⁶⁹. Family members are involved in the evaluation and treatment processes.

Appropriate caution must be taken during chronic pain syndrome treatment in patients who exhibit any of the following behaviors:

Poor response to prior appropriate management
Unusual, unexpected response to prior specific treatment
Avoidance of school, work, or other social responsibility
Severe depression
Severe anxiety disorder
Excessive pain behavior
Physician shopping
Noncompliance with treatment in the past
Drug abuse or dependence
Family, marital, or sexual problems
History of physical or sexual abuse

National health professional organizations have issued guidelines for treating several chronic pain syndrome ⁷⁰.

Hospitalization usually is not required for patients with chronic pain syndrome, but it depends on how invasive the treatment choice is for pain control and on the severity of the case.

Patients with chronic pain syndrome generally are treated on an outpatient basis and require a variety of health care professionals to manage their condition optimally.

A clinical practice guideline from the American College of Physicians ⁷¹ encourages the use of non-pharmacologic approaches as initial treatment for chronic low-back pain. The options they suggest include several complementary approaches—acupuncture, mindfulness-based stress reduction, tai chi, yoga, progressive relaxation, biofeedback, and spinal manipulation—as well as conventional methods such as exercise and cognitive behavioral therapy.

The American College of Rheumatology ⁷² mentions several complementary approaches in its guidelines for the management of osteoarthritis of the hip or knee. For osteoarthritis of the knee, the guidelines mention tai chi as one of several nondrug approaches that might be helpful. The same guidelines, however, discourage using the dietary supplements glucosamine and chondroitin for osteoarthritis of the hip or knee.

The American College of Gastroenterology ⁷³ included probiotics/prebiotics, peppermint oil, and hypnotherapy in its evaluation of approaches for managing irritable bowel syndrome. The American College of Gastroenterology found only weak evidence that any of these approaches may be helpful.

Table 2. Chronic Pain Treatment Options

Non-Drug Options	Nociceptive	Neuropathic	Central Sensitization
Consider in all patients
Increased Activity/Exercise (aerobic, strength, flexibility/balance)	In addition to helping generally across types of pain, specifically:
	Knee and hip osteoarthritis Rheumatoid arthritis Vascular claudication,	Chemotherapy induced neuropathy Diabetic peripheral neuropathy Multiple sclerosis	Fibromyalgia (for pain, aerobic exercise rather than resistance exercise)
Improve Sleep	All types of pain
Dietary Modification	For all types of pain: Mediterranean pattern of eating
Self-regulatory and psychophysiological approaches	For all types of pain: biofeedback, relaxation training, and hypnosis
Consider in select patients based on diagnosis and interest
Acupuncture	Osteoarthritis, chronic neck and low back pain, Headache	Post-herpetic neuralgia, chemotherapy induced polyneuropathy	Fibromyalgia
Physical Therapy	Functional deficits or secondary pain generators that directed therapy may improve (based on functional deficits rather than diagnosis)
Transcutaneous electrical stimulation (TENS)	Rheumatoid arthritis Knee osteoarthritis	Diabetic peripheral neuropathy Post herpetic neuralgia	Fibromyalgia
Massage	Low back pain Knee osteoarthritis Neck pain Hand osteoarthritis		Fibromyalgia
Mindfulness Based Stress Reduction	Low back pain Rheumatoid arthritis		Fibromyalgia
Cognitive behavioral therapy (CBT)	Low back pain Neck pain Knee pain Shoulder pain Hip pain, Hip osteoarthritis Knee osteoarthritis Rheumatoid arthritis Systemic lupus erythematosus Temporomandibular joint pain.		Fibromyalgia
Acceptance and commitment therapy (ACT)	Low back pain Rheumatoid arthritis		Fibromyalgia

[Source ⁷⁴ ]

Regular exercise

Extensive research on physical inactivity in patients with chronic pain has revealed that the majority experience a reduction in overall physical activity levels due to the impact of chronic pain ⁷⁵, ⁷⁶, ⁷⁷, ⁷⁸. The more debilitating the pain, the lower the engagement in physical activity ⁷⁹.

People who have chronic pain are advised to stay physically active and get regular exercise ⁸⁰, ⁸¹. According to the available evidence, physical activity did not cause harm in people with chronic pain ⁸¹. When you exercise, your body releases substances that have a pain-relieving effect. Exercise also improves your blood circulation and stimulates your metabolism, making sure that your bones and cartilage get enough nutrients. It has other advantages too: exercise improves your physical resilience, your ability to move and your sense of balance, which can help to prevent falls in old age. Last, but not least, it can improve your wellbeing.

The National Institute for Health and Care Excellence (NICE) osteoarthritis guidelines state that “for all people with osteoarthritis, offer therapeutic exercise tailored to their needs for example, local muscle strengthening, general aerobic fitness” ⁸²:

doing regular and consistent exercise, even though this may initially cause pain or discomfort, will be beneficial for their joints
long-term adherence to an exercise plan increases its benefits by reducing pain and increasing functioning and quality of life.

People who aren’t used to exercising should start off slowly to avoid overdoing it. You can find out what type of exercise helps you by either trying out different things yourself or as part of exercise-based treatment. The aim of exercise-based treatment is to gradually increase your pain threshold again. There are special programs for a number of pain syndromes such as rheumatoid arthritis, fibromyalgia and chronic back pain, for example organized by support groups. In Germany, doctors can also prescribe something known as functional training for up to 24 months.

Diet and Weight Management

Diet represents another modifiable lifestyle factor of significant importance to patients with chronic pain ⁸³. Poor dietary habits can be considered as adverse lifestyle factors that partly account for the observed excess mortality among people with chronic pain ⁸⁴, ⁸⁵. Research indicates that the dietary quality of individuals with chronic pain tends to be lower than that of those without pain ⁸⁶, ⁸⁷, ⁸⁸. Evidence suggests that nutrition should be considered within a personalized approach to pain management ⁸⁹.

Collectively, unhealthy dietary patterns, overweight and obesity are increasingly acknowledged as viable targets for therapeutic intervention in individuals with chronic pain ⁹⁰, ⁹¹, ⁹², ⁹³, ⁹⁴. Poor dietary habits often but not always relate to overweight or obesity ⁹⁵. Meta-analyses confirm a positive association between overweight, obesity and low back pain ⁹⁵, ⁹⁶, ⁹⁷, ⁹⁸, ⁹⁰, ⁹¹, ⁹⁹, with a higher body mass index (BMI) and fat mass correlating with increased prevalence of chronic pain ⁵⁵. Furthermore, overweight and obesity contribute to more intense and debilitating chronic pain, as evidenced by dose–response relationships between pain intensity, disability, body mass index (BMI), waist circumference, percent fat and fat mass in individuals with chronic low back pain ⁹¹. In terms of socioeconomic impact, overweight and obesity correlate not only with persistent chronic pain but also with elevated healthcare-seeking rates for pain-related issues ⁹⁵. Individuals who are obese or overweight and experiencing chronic pain are likely to have more health needs that necessitate a focus on behavioral lifestyle factors ⁹².

Studies involving overweight and obese adults with knee osteoarthritis demonstrate that a combination of diet and exercise therapy can yield moderate pain relief and improved physical function ¹⁰⁰. In a more recent randomized controlled trial ¹⁰¹, three interventions were compared: exercise alone, intensive diet-induced weight loss alone and a combination of intensive diet-induced weight loss with exercise. The study revealed that in comparison to exercise alone, diet-induced weight loss led to substantial reductions in load bearing at the hip, knee and ankle joints ¹⁰¹. However, when diet was combined with exercise, these reductions were less pronounced, although they remained significantly superior to the results achieved with exercise alone ¹⁰¹. Additionally, it is worth noting that diet and exercise therapy, when integrated into standard care, have proven to be cost-effective for such patients ¹⁰².

Weight management programs should include changes in dietary and physical activity behaviors (i.e., a self-management behavioral approach to balance caloric intake and physical activity) to comply with evidence-based standards rather than strict and harsh calorie restriction diets ⁹⁴. This should involve the integration of behavioral changes to support and facilitate calories balance-related behavior ¹⁰³. The American College of Sports Medicine (ACSM) emphasize the combination of a moderate dietary restriction and a physical activity program is effective and yields longterm outcomes ¹⁰⁴. Adopting a self-management approach to enhance behaviors related to calories balance can be seamlessly incorporated into the previously outlined cognition-targeted exercise therapy program. This implies that assessing daily physical activity and exercise levels will be geared toward not only weight reduction but also the simultaneous improvement of pain-related cognitions. Consequently, the exercises and daily physical activities can be aligned with the principles of cognition-targeted treatment as well as the personalized approaches for weight reduction ⁸⁹.

While specific recommendations may vary based on individual needs, general guidelines for dietary interventions in chronic pain advocate for the inclusion of colorful fruits and vegetables, along with an adequate intake of high-quality fats to reduce inflammation and oxidative stress ⁸⁶. Additionally, preventing deficiencies in Vitamin D, Vitamin B12 and Magnesium has the potential to contribute to pain alleviation ⁸⁶, ¹⁰⁵, ¹⁰⁶. Lastly, ensuring sufficient fiber intake proves significant for promoting proper digestion, maintaining a healthy microbiome, managing weight and subsequently influencing chronic pain ⁸⁶.

Complementary medicine

Some recent research has looked at the effects of complementary approaches on chronic pain syndrome in general rather than on specific painful conditions. A growing body of evidence suggests that some complementary approaches, such as acupuncture, hypnosis, massage, mindfulness meditation, spinal manipulation, tai chi, and yoga, may help to manage some painful conditions.

A 2017 review ¹⁰⁷ looked at complementary approaches with the opioid crisis in mind, to see which ones might be helpful for relieving chronic pain and reducing the need for opioid therapy to manage pain. There was evidence that acupuncture ¹⁰⁸, yoga, relaxation techniques, tai chi, massage, and osteopathic or spinal manipulation ¹⁰⁹ may have some benefit for chronic pain, but only for acupuncture was there evidence that the technique could reduce a patient’s need for opioids.
Research shows that hypnosis is moderately effective in managing chronic pain, when compared to usual medical care. However, the effectiveness of hypnosis can vary from one person to another.
A 2017 review of studies of mindfulness meditation for chronic pain showed that it is associated with a small improvement in pain symptoms.
Studies have shown that music can reduce self-reported pain and depression symptoms in people with chronic pain ¹¹⁰.
Massage therapy is manual manipulation of muscles and connective tissue to enhance physical rehabilitation and improve relaxation. Massage therapy can reduce pain scores for patients with low back pain, knee osteoarthritis, juvenile rheumatoid arthritis, chronic neck pain, and fibromyalgia ¹¹¹, ¹¹². Not yet determined are the optimal number, duration and frequency of massage sessions for treating pain.
Transcutaneous electrical nerve stimulation (TENS). Transcutaneous electrical nerve stimulation (TENS) uses low-voltage electrical currents to relieve pain. A TENS unit is a small device that delivers the current at or near your nerves to block or change your perception of pain. Researchers are still working to find out more information. Healthcare providers use TENS to treat a range of conditions, including osteoarthritis, tendinitis and fibromyalgia. Most experts believe the electrical current helps release pain-reducing chemicals that your own body produces. Evidence is limited for the efficacy of TENS in pain management ¹¹³. However, it is relatively safe, with units relatively available and easy to use.

Although the mind and body practices studied for chronic pain have good safety records, that doesn’t mean that they’re risk-free for everyone. Your health and special circumstances (such as pregnancy) may affect the safety of these approaches. If you’re considering natural products, remember that natural doesn’t always mean safe and that some natural products may have side effects or interact with medications.

Mind and body practices, such as acupuncture, hypnosis, massage therapy, mindfulness/meditation, relaxation techniques, spinal manipulation, tai chi/qi gong, and yoga, are generally safe for healthy people if they’re performed appropriately.

People with medical conditions and pregnant women may need to modify or avoid some mind and body practices.
Like other forms of exercise, mind and body practices that involve movement, such as tai chi and yoga, can cause sore muscles and may involve some risk of injury.
It’s important for practitioners and teachers of mind and body practices to be properly qualified and to follow appropriate safety precautions.

Table 3. Herbal Supplements used in Chronic Pain

Name	Proposed Indication	Proposed Effect	Side Effects/Notes
Arnica (Arnica montana) (topical) ⁴²	Low back pain – acute flares Muscle pain Osteoarthritis	Anti-inflammatory	Oral use may be toxic
Boswellia serrata ¹¹⁴	Osteoarthritis	Anti-inflammatory
Cannabinoids (medicinal cannabis) ¹¹⁵	Neuropathic pain Osteoarthritis Headache	cannabidiol (CBD): Anti-inflammatory THC: Central nervous system mediated	Quality of evidence is low to date with only real benefit a mild one in pain reduction for neuropathic pain. cannabidiol (CBD) may play an anti-inflammatory role, with THC causing most adverse effects. Consider advising patients who are planning to use for pain management to start with low dose cannabidiol (CBD) alone.
Cayenne pepper (Capsicum annuum) (topical) ⁴²	Low back pain –acute flares	Analgesic Anti-Inflammatory	Equal to placebo
Devil’s claw (Harpagophytum procumbens) 60-100 mg (standardized hapagosides) / day in divided dosing (Harpagophutum) ¹¹⁵	Low back pain – acute flares	Analgesic Anti-inflammatory	No evidence for use in other pain conditions
Glucosamine and chondroitin ⁴⁴	Osteoarthritis		May interact with warfarin. Does not treat pain from knee or hip OA. Does not slow the progression of knee or hip OA. Does not have disease modifying effects in knee or hip OA.
Turmeric (Curcumin) ¹¹⁶	Osteoarthritis	Anti-inflammatory	Case reports of antiplatelet effect but only clinical trial showed no impact on bleeding or INR.
Willow bark 120 to 240 mg/day ⁴²	Low back pain – acute flares	Analgesic Anti-inflammatory	Contains salicin, an aspirin precursor. Avoid if allergic to ASA or NSAIDs.

Footnotes: * Always check with your doctor for potential interactions of herbal supplements with prescription medications or other non-prescription medications or supplements.

[Source ⁷⁴ ]

Chronic pain medications

Some medicines can play a role in managing chronic pain. Sometimes, medicines won’t relieve all your pain symptoms. It’s important to work with a doctor or pain specialist to identify a range of strategies you can use, to reduce the way pain impacts your life.

Acetaminophen (paracetamol) — this very effective pain-relief medicine is sometimes taken along with other medicines. Acetaminophen is thought to block the production of prostaglandins in the central nervous system. Prostaglandins are hormonelike substances that are involved in pain and inflammation. Acetaminophen is usually recommended as a first line treatment for mild to moderate pain. Acetaminophen might be taken for pain due to a skin injury, headache, or conditions that affect the muscles and bones. Acetaminophen is often prescribed to help manage osteoarthritis and back pain. Do not take more than the daily dose listed on the package. Speak to your doctor if acetaminophen (paracetamol) is not managing your pain. Acetaminophen is not as effective as nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of knee and hip pain related to osteoarthritis.
Non-steroidal anti-inflammatory drugs (NSAIDs) — medicines such as ibuprofen (Advil, Motrin IB, others), naproxen sodium (Aleve) and diclofenac may help manage pain. Try to take them at the lowest possible dosage for the shortest possible time, as they can have serious side effects. But if you take more than the recommended dosage, NSAIDs may cause nausea, stomach pain, stomach bleeding or ulcers. Sometimes this can happen even when you take the recommended dosage.
Antidepressants — some medicines that are used to treat depression, such as tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), are also sometimes prescribed by doctors to reduce pain.
- Tricyclic antidepressants (TCAs) used in the treatment of chronic pain include amitriptyline and nortriptyline (Pamelor).
- Serotonin and norepinephrine reuptake inhibitors (SNRIs), that may be prescribed to relieve chronic pain include duloxetine (Cymbalta, Drizalma Sprinkle), venlafaxine (Effexor XR, Pristiq) and milnacipran (Fetzima, Savella).
Anticonvulsants or antiepileptic medicines — medicines that are commonly used to treat epilepsy can also help manage nerve pain. Anti-seizure medications used to treat chronic nerve pain include gabapentin (Gralise, Neurontin, Horizant) and pregabalin (Lyrica). These medications treat the burning pain of shingles, known as postherpetic neuralgia. And they treat pain related to nerve damage in the legs and feet due to diabetes, known as diabetic neuropathy. Anti-seizure medications quiet pain signals from nerve cells. They may be helpful for stabbing or shooting pain from nerve damage.
Muscle relaxants. Sedating or non-sedating muscle relaxants are often prescribed for chronic myofascial pain, despite little or no evidence for a long-term benefit ¹¹⁷. Cyclobenzaprine, tizanidine, and metaxalone can cause significant sedation, while methocarbamol is less likely to do so. Benzodiazepines pose a significant risk for long-term dependence and misuse, and they substantially increase the danger of overdose when used together with opioids. Baclofen, while somewhat useful for spasticity, has little role as a muscle relaxant, poses a significant risk for dependence, and should generally be avoided.
Topical agents. Topical NSAIDs and anesthetics are occasionally useful in nociceptive or neuropathic pain syndromes. They can be expensive and are often not covered by insurance. Topical NSAIDs benefit a minority of osteoarthritis patients. They generally are not useful in other types of pain ¹¹⁸, ¹¹⁹. Topical lidocaine patches (prescribed or over-the-counter) can be effective. Ointment is less effective and can be messy. Both are expensive and often not covered by insurance. Over the counter 4% lidocaine cream is not expensive, but only marginally effective. Capsaicin cream (1%, not 0.25%) can be modestly effective, is available without prescription, but requires care in application to avoid unwanted burning. Compounded capsaicin 8% cream is more effective, but the cost may be prohibitive. When other treatments have failed, topical nitroglycerin may have some effect for wound pain, anal fissure pain, vulvodynia, and diabetic neuropathy. Headache can complicate treatment with nitroglycerin. Avoid nitroglycerin in patients who use phosphodiesterase type 5 inhibitors (avanafil, sildenafil, tadalafil, vardenafil) for erectile dysfunction. Compounded topical 5% morphine can provide local wound analgesia and may promote healing. It is only available at compounding pharmacies and can be expensive.
Opioids — strong pain-relief medicines, such as morphine, fentanyl (Actiq, Fentora), oxycodone (OxyContin, Roxicodone, others), codeine, hydrocodone (Hysingla ER), hydrocodone-acetaminophen, oxycodone-acetaminophen (Percocet), might be prescribed by a doctor for short periods of time for acute pain, but are not effective in chronic pain that is not caused by cancer. Deciding whether to prescribe opioids is based on an assessment of benefits and harms. Opioids are not usually recommended for most types of chronic pain ¹²⁰. This is because opioids are proven to not be effective at treating chronic pain not caused by cancer. Research shows that over time your body adapts to these medications and they bring less and less pain relief. This is known as tolerance. It means that you need more of the medication to achieve the same degree of pain relief. Long-term use of opioids may lead to dependence on the medications and, eventually, addiction. The longer you use opioids, the greater the risk of becoming addicted. But even using opioids to manage pain for more than a few days increases your risk. Researchers have found that the odds of being on opioids a year after starting a short course increases after only five days on the medication.

Many medications commonly used to treat chronic pain carry potential risks, side effects, and possible complications. Acetaminophen (paracetamol) is a standard pharmacological therapy for patients with chronic pain, taken either as a single agent or in combination with an opioid. However, liver toxicity can occur, especially with doses exceeding 4 grams per day, making it the most common cause of acute liver failure in the US ¹²¹, ¹²². Furthermore, liver toxicity can occur at therapeutic doses for patients diagnosed with chronic liver disease ¹²³.

Frequently used add-on (adjunct) medications such as gabapentin or pregabalin can cause sedation, swelling, mood changes, confusion, and respiratory depression in older patients who require additional pain relievers ¹²⁴. Add-on (adjunct) medications such as gabapentin or pregabalin require caution in older patients with painful diabetic neuropathy. Moreover, combining gabapentin or pregabalin with opioid analgesics has been shown to increase death rate of patients ¹²⁵.

Duloxetine can cause mood changes, headaches, nausea, and other possible side effects and should be avoided in patients with a history of kidney or liver disease. Patients with these conditions should be closely monitored if duloxetine is prescribed.

Feared complications of opioid therapy include addiction, overdose resulting in respiratory compromise, and occasionally, death. However, opioid-induced hyperalgesia is also a significant concern, where patients become more sensitive to painful stimuli while on chronic opioids ¹²⁶. The long-term risks and side effects of opioids include constipation, tolerance, dependence, nausea, dyspepsia, arrhythmia (methadone treatment QT prolongation), and opioid-induced endocrine dysfunction, which can result in amenorrhea, impotence, gynecomastia, and decreased energy and libido ¹. Additionally, there appears to be a dose-dependent risk of opioid overdose with increasing daily milligram morphine equivalents ¹.

Table 4. Chronic pain medications

Medication	May Benefit	Potential Co-treatment Of	Harms	Cost	Comments
Acetaminophen (paracetamol)	Nociceptive	Headaches	May exacerbate chronic daily headaches	Low	May be synergistic when combined with NSAIDs
Non-steroidal anti-inflammatory drugs (NSAIDs)	Nociceptive	Headaches	Gastrointestinal bleeding, acute kidney injury, chronic kidney disease, increased risk for coronary artery events	Low	May increase blood pressure; edema. COX-2 inhibitor somewhat decreases risk of gastrointestinal bleeding
Serotonin and norepinephrine reuptake inhibitors (SNRIs) antidepressants Duloxetine, venlafaxine, milnacipran	Central pain sensitization (Type 1) pains, neuropathic pain, non-specific low back pain, functional abdominal pain	Anxiety Depression	Weight gain, urinary retention, withdrawal symptoms (taper down to discontinue)	Low/Moderate	Duloxetine FDA-approved for diabetic neuropathy, fibromyalgia Duloxetine more effective than venlafaxine
Anticonvulsants Gabapentin Pregabalin Topiramate	Neuropathic pain, fibromyalgia Neuropathic pain	Gabapentin: menopausal hot flushes Migraine prophylaxis	Weight gain, edema, fatigue Cognition and speech problems	Gabapentin: Low Pregabalin: Low Topiramate: Moderate	Gabapentin: not effective in low back pain Pregabalin: FDA-approved for diabetic neuropathy, fibromyalgia
Tricyclic antidepressants (TCAs)	Central, neuropathic	Anxiety, depression, insomnia, migraine prophylaxis, smoking cessation	Fatigue, weight gain, constipation	Low	Give in early evening when sleep initiation is an issue
Muscle relaxants Cyclobenzaprine, methocarbamol, tizanidine, Benzodiazepines (BZD), carisoprodol, Baclofen	Muscle spasms Spasticity		Fatigue Sedation, dependence Same as benzodiazepines	Low/High	Not effective for acute or chronic back pain. Benzodiazepines, carisoprodol (Soma): neither indicated nor effective – high risk for dependence Same as benzodiazepines
Topical Agents Non-steroidal anti-inflammatory drugs (NSAIDs)Lidocaine ointment or patch Capsaicin cream Nitroglycerin	Osteoarthritic (OA) joints OA joints, focal neuropathic pain Same as lidocaine Wound, anal fissure pain, vulvodynia, diabetic neuropathy		Headaches	High/Very High High/Very High Low Low	Ointment is messy. Patches often not covered by insurance Do not use nitroglycerin in patients using PDE-5 erectile dysfunction medications

[Source ⁷⁴ ]

Managing your chronic back pain

Managing chronic pain means finding ways to make your back pain tolerable so you can live your life ¹²⁷. You may not be able to get rid of your pain completely, but you can change some things that worsen your pain. These things are called stressors. Some of them may be physical, like the chair you sit in at work. Some may be emotional, like a difficult relationship.

Reducing stress can improve your physical and emotional health. It is not always easy to reduce stress, but it’s easier if you are able to ask your friends and family for help.

Make a List

First, make a list of what makes your back pain better and what makes it worse.

Then try to make changes in your home and work to decrease the causes of your pain. For example, if bending to pick up heavy pots sends shooting pain down your back, rearrange your kitchen so that the pots are hanging from above or are stored at waist height.

If your back pain is worse at work, talk to your boss. It may be that your workstation isn’t set up correctly.

If you sit at a computer, make sure that your chair has a straight back with an adjustable seat and back, armrests, and a swivel seat.
Ask about having an occupational therapist assess your workspace or movements to see if changes such as a new chair or cushioned mat under your feet would help.
Try not to stand for long periods. If you must stand at work, rest one foot on a stool, then the other foot. Keep switching the load of your body’s weight between your feet during the day.

Long car rides and getting in and out of the car can be hard on your back. Here are some tips:

Adjust your car seat to make it easier to enter, sit in, and get out of your car.
Bring your seat as far forward as possible to avoid leaning forward when you are driving.
If you drive long distances, stop and walk around every hour.
DO NOT lift heavy objects right after a long car ride.

These changes around your home could help relieve your back pain:

Raise your foot up to the edge of a chair or stool to put your socks and shoes on instead of bending over. Also consider wearing shorter socks. They are quicker and easier to put on.
Use a raised toilet seat or install handrail next to the toilet to help take pressure off your back when you sit on and get up from the toilet. Also make sure the toilet paper is easy to reach.
DO NOT wear high-heeled shoes. If you must wear them sometimes, consider wearing comfortable shoes with flat soles to and from the event or until you must put on high-heels.
Wear shoes with cushioned soles.
Rest your feet on a low stool while you’re sitting so that your knees are higher than your hips.

Pain Relievers and Medicines

Pain relievers are medicines that reduce or relieve headaches, sore muscles, arthritis, or other aches and pains. There are many different pain medicines, and each one has advantages and risks. Some types of pain respond better to certain medicines than others. Each person may also have a slightly different response to a pain reliever.

Over-the-counter (OTC) medicines are good for many types of pain. There are two main types of OTC pain medicines: acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin, naproxen (Aleve), and ibuprofen (Advil, Motrin) are examples of OTC NSAIDs. If you take OTC pain medicines, make sure you do read and follow the instructions on the box.

If OTC medicines don’t relieve your pain, your doctor may prescribe something stronger or long-acting medicines for constant pain. Many NSAIDs are also available at higher prescription doses. The most powerful pain relievers are opioids. They are very effective, but they can sometimes have serious side effects. There is also a risk of addiction. Because of the risks, you must use them only under a doctor’s supervision.

There are many things you can do to help ease pain. Pain relievers are just one part of a pain treatment plan.

Your doctor might recommend a prescription pain reliever. Be sure to follow his or her instructions for how to take the medicine. Many prescription pain relievers are opioids. Opioids can be very effective when taken as directed. But many people who misuse opioids become addicted. Opioid addiction is a very serious health issue that can lead to death.

Rely on Friends and Family

It is important to have strong relationships with family and friends you can depend on when your back pain makes it hard to get through the day.

Take time to build strong friendships at work and outside of work by using caring words and being kind. Give sincere compliments to the people around you. Respect those around you and treat them the way you like to be treated.

If a relationship is causing stress, consider working with a counselor to find ways to resolve conflict and strengthen the relationship

Establish Life Routines

Set up good life habits and routines such as:

Exercise a little every day. Walking is a good way to keep your heart healthy and your muscles strong. If walking is too hard for you, work with a physical therapist to develop an exercise plan that you can do and maintain.
Eat foods that are low in fats and sugar. Healthy foods make your body feel better, and they decrease your risk of being overweight, which can cause back pain.
Reduce demands on your time. Learn how to say yes to things that are important and no to those that are not.
Prevent pain from starting. Figure out what causes your back pain, and find other ways to get the job done.
Take medicines as needed.
Make time for activities that make you feel relaxed and calm.
Give yourself extra time to get things done or to get where you need to go.
Do things that make you laugh. Laughter can really help reduce stress.
Getting regular sleep at night and not taking daytime naps should help.
Stopping smoking also helps, because the nicotine in cigarettes can make some medicines less effective. Smokers also tend to have more pain than nonsmokers ⁴⁰.

What is Complex Regional Pain Syndrome?

Complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy or causalgia, is a chronic (lasting greater than 3 months) pain condition that is regional pain (not in a specific nerve territory or dermatome) most often affects one limb (arm, leg, hand, or foot) usually after an injury, a surgery, a stroke or a heart attack ¹²⁸, ¹²⁹, ¹³⁰, ¹³¹, ¹³², ¹³³, ¹³⁴, ¹³⁵, ¹³⁶, ¹³⁷. The pain is out of proportion to the severity or duration to the usual course of pain after such tissue trauma ¹³⁸. For example, complex regional pain syndrome is a syndrome that can occur after simple injuries such as a sprained ankle or a broken arm. Complex regional pain syndrome (CRPS) is characterized by signs indicating autonomic and neuro-inflammatory changes in the affected body region varying between patients and over time. Complex regional pain syndrome is characterized by prolonged or excessive pain and changes in skin color, temperature, stiffness, weakness and/or swelling in the affected area. Often, complex regional pain syndrome (CRPS) is accompanied by significant emotional distress or functional disability. Complex regional pain syndrome is believed to be caused by damage to or malfunction of, the peripheral nervous system (nerves that are located outside of your brain and spinal cord) and central nervous system (brain and spinal cord) ¹³⁹, ¹⁴⁰, ¹³¹, ¹⁴¹. Complex regional pain syndrome is almost three or four times more common in women than in men, and peaks in onset between the ages of 50 and 70 years ¹⁴². Given the changes in diagnostic criteria and the evolving understanding of complex regional pain syndrome process, studies vary on the actual incidence of complex regional pain syndrome. The overall incidence rates of complex regional pain syndrome can range anywhere from approximately 5 to 29 per 100,000 people each year, with the highest incidence typically occurring in females between 61 and 70 years of age ¹⁴³, ¹⁴⁴, ¹⁴⁵. Based on the epidemiological studies available, complex regional pain syndrome appears to be more common in patients of North European ancestry, although it does appear to occur frequently in those of South Korean ancestry as well ¹⁴⁴, ¹⁴⁵. In the United States, it is estimated that there are at least 50,000 cases of complex regional pain syndrome type 1 each year ¹⁴⁶. Similarly, with the variation in complex regional pain syndrome diagnostic criteria over the years the incidence among patients with fractures is anywhere from 0.05% to 0.2% in older studies and 3% to 7% in more recent studies ¹⁴⁷. The upper extremity is affected more frequently than the lower extremity ¹⁴⁴.

Signs and symptoms of complex regional pain syndrome include:

Continuous burning or throbbing pain, usually in your arm, leg, hand or foot
Sensitivity to touch or cold
Swelling of the painful area
Changes in skin temperature — alternating between sweaty and cold
Changes in skin color, ranging from white and mottled to red or blue
Changes in skin texture, which may become tender, thin or shiny in the affected area
Changes in hair and nail growth
Joint stiffness, swelling and damage
Muscle spasms, tremors, weakness and loss (atrophy)
Decreased ability to move the affected body part

Symptoms may change over time and vary from person to person. Pain, swelling, redness, noticeable changes in temperature and hypersensitivity particularly to cold and touch usually occur first.

Over time, the affected limb can become cold and pale. It may undergo skin and nail changes as well as muscle spasms and tightening. Once these changes occur, the condition is often irreversible.

Complex regional pain syndrome occasionally may spread from its source to elsewhere in your body, such as the opposite limb.

In some people, signs and symptoms of complex regional pain syndrome go away on their own. In others, signs and symptoms may persist for months to years. Treatment is likely to be most effective when started early in the course of the illness.

Complex regional pain syndrome is divided into two types ¹⁴⁸:

Complex regional pain syndrome type 1: Individuals without a confirmed nerve injury are classified as having Complex regional pain syndrome type 1 (previously known as reflex sympathetic dystrophy syndrome).
Complex regional pain syndrome type 2: Complex regional pain syndrome type 2 (previously known as causalgia) is when there is an associated, confirmed nerve injury.

As some research has identified evidence of nerve injury in complex regional pain syndrome type 1, it is unclear if this disorder will always be divided into two types ¹⁴⁹, ¹⁵⁰, ¹⁵¹, ¹⁵², ¹⁵³. Nonetheless, the treatment is similar. Both subtypes of complex regional pain syndrome are characterized by severe pain that is disproportionate to the inciting event, most commonly affecting the hand or foot but which can spread to other body regions ¹⁵⁴. Additionally complex regional pain syndrome presents with some or all of the following symptoms in the affected body parts: sensory disturbances, temperature changes, abnormal patterns of sweating, swelling and edema, reduced joint range of motion, movement abnormalities such as weakness, tremor or dystonia, trophic changes such as skin atrophy or altered hair and nail growth, and localized osteoporotic changes ¹⁵⁵; and alterations in body perception or schema ¹⁵⁶.

Complex regional pain syndrome is often described in terms of “warm” changes and “cold” changes, although they are not separate diagnostic categories. Warm complex regional pain syndrome is associated with a warm, redness of the skin, swelling of extremity and tends to be correlated with inflammatory changes earlier in the disease course; one study described these changes within the first eight months ¹⁵⁷. Cold complex regional pain syndrome is associated with a cold, dusky, sweaty extremity and is more often associated with chronic complex regional pain syndrome; in one study, cold symptoms lasted for more than nine months ¹⁵⁷. The same extremity can have both warm and cold symptoms, and the disease pattern and clinical course vary among patients ¹⁵⁸, ¹⁵⁹, ¹⁶⁰.

Complex regional pain syndrome symptoms vary in severity and duration, although some cases are mild and eventually go away. In more severe cases, individuals may not recover and may have long-term disability.

Although it is more common in women, complex regional pain syndrome can occur in anyone at any age, with a peak at age 40. Complex regional pain syndrome is rare in the elderly. Complex regional pain syndrome is uncommon in children under age 10.

At the consensus meeting of the International Association for the Study of Pain (IASP) in Budapest in 2004, the Budapest criteria for the diagnosis of complex regional pain syndrome were developed ¹⁶¹, ¹⁵⁹. In an effort to enhance specificity, the Budapest clinical diagnostic criteria for complex regional pain syndrome included both symptoms and signs of the disease. The Budapest criteria is 99% sensitive and 68% specific for complex regional pain syndrome, with increased sensitivity as other diagnoses are ruled out ¹⁶¹, ¹⁶². The Budapest criteria were formally accepted by the International Association for the Study of Pain (IASP) in 2012 after more robust validation testing ¹⁶³. It should be noted that a 4 of 4 symptom decision rule is recommended when applying the Budapest criteria for research purposes ¹⁶². The Budapest criteria, are listed in Table 1 below.

Additional clinical findings in complex regional pain syndrome ¹⁶⁴:

Allodynia
- pain on light movement/touch/pressure
  (e.g., draught, brush, finger [pressure less than 100 g/cm² or load less than 500 g])
- pain from vibration (e.g. tuning fork on a bony prominence), cold, heat
Hyperalgesia
- periarticular pressure hyperalgesia distal to the site of injury/surgery
- solitary sharp stimulus (pinprick) is felt stronger/longer
Disturbance of body perception/interoception
- attention: exerted, hypervigilant focussing or disregarding (neglect-like/dissociation)
- shape, size, weight, position, posture, laterality, symmetry, ownership, e.g., as if limbs were detached, foreign, dead (“as if wooden”, “like part of a dead body”)
- attribution of meaning or affective evaluation, e.g., threatening, disgusting, or hated limb; caution: desire for amputation
Functional disturbances of voluntary motor function
- protective posture, slowed, reduced or non-movement
- reduced experience of motor action, control, intention (agency)
- weakness, disturbances of fine motor skills, coordination or movement
- sometimes several types of disturbance inone and the same limb, e.g.
  - myoclonus or tremor (with “entrainment”, i.e. unconscious synchronization with rhythmic movements of the unaffected limb)
  - dystonia (usually in fixed flexion/supination)
- increase during manipulation, decrease when distracted, no decrease with sensory tricks
Trophic, vasomotor and sudomotor disturbances
- non-pitting edema (circumference measurements where possible)
- skin color usually reddish-blue, with time more waxy-pale
- skin temperature about 1–2 degrees difference to the contralateral side
- hair growth: usually increased, thick, dark, sometimes reduced, finer hair
- nail growth: usually harder, brittle, faster or slower nail growth
- increased, with time reduced, sweating
- trophic skin lesions or pressure lesions
Tendency to spread and become generalized
- at times tendency to spread proximally or to other limbs
- other pain sites; contralateral and generalized reduced pain threshold/body image disturbance
- sensitivity to noise, light, smell, touch, at times with autonomic arousal
- cardiovascular dysregulation, increased heart rate, reduced heart rate variability
- micturition and digestive problems
Affective, cognitive, general signs and symptoms; behavioral changes
- fear, particularly of touch, movement, and disease progression
- avoidance of sensory stimuli from clothes, wind, movement, other people, etc.
- signs and symptoms of trauma-related disorders (helplessness, flashbacks, dissociation, depersonalization, avoidance, hypervigilance/hyperarousal)
- mood fluctuations, depressiveness, alexithymia (reduced awareness of one’s own emotions and those of others), withdrawal
- fatigue, sleeping problems, and cognitive disturbances

Table 1. The Budapest clinical diagnostic criteria for complex regional pain syndrome

1. Continuing pain, which is disproportionate to any inciting event

2. Must report at least one symptom in all four following categories

Sensory: reports of hyperesthesia (a symptom that involves extreme sensitivity in your sense of touch) and/or allodynia (a condition where a stimulus that normally wouldn’t cause pain results in pain. e.g., a light touch from a feather might cause pain instead of just a sensation)
Vasomotor: reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry
Sudomotor or edema: reports of edema and/or sweating changes and/or sweating asymmetry
Motor or trophic: reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

3. Must display at least one sign at time of evaluation in two or more of the following categories

Sensory: evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
Vasomotor: evidence of temperature asymmetry and/or skin color changes and/or asymmetry
Sudomotor or edema: evidence of edema and/or sweating changes and/or sweating asymmetry
Motor or trophic: evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

4. There is no other diagnosis that better explains the signs and symptoms

[Source ¹⁶⁵ ]

Figure 1. Complex regional pain syndrome pathophysiology

Footnotes: Pathophysiological connections in the complex regional pain syndrome. An insulting event triggers classic and neurogenic inflammation, which are responsible for the inflammatory signs at least of the warm phase and, perhaps, contribute to the autonomic dysfunction. Autonomic dysfunction is also responsible for several aspects of the syndrome, while interventions targeting it have been beneficial, mainly in case series. Central nervous system (brain and spinal cord) plasticity and psychological factors likely complete the process. However, the exact mechanisms eliciting the central nervous system (brain and spinal cord) changes, linking to the psychological factors and ultimately implicating both of these factors to the clinical presentation of the syndrome are still obscure.

[Source ¹⁴⁸ ]

Complex regional pain syndrome causes

It is unclear why some individuals develop complex regional pain syndrome while others with similar trauma do not ¹⁶⁶, ¹⁶⁷, ¹⁶⁸. In more than 90 percent of cases, complex regional pain syndrome is triggered by a clear history of trauma or injury ¹⁶⁹, ¹⁷⁰, ¹⁷¹. The most common triggers are fractures, sprains/strains, soft tissue injury (such as burns, cuts, or bruises), limb immobilization (such as being in a cast), surgery, or even minor medical procedures such as needle stick. Although complex regional pain syndrome can develop after any injury, the most common initiating events are fractures, surgery, crush injuries, and sprains ¹⁷². Complex regional pain syndrome represents an abnormal response that magnifies the effects of the injury. Some people respond excessively to a trigger that causes no problem for other people, such as what is observed in people who have food allergies.

Peripheral nerve abnormalities found in individuals with complex regional pain syndrome usually involve the small unmyelinated and thinly myelinated sensory nerve fibers (axons) that carry pain messages and signals to blood vessels. Myelin is a mixture of proteins and fat-like substances that surround and insulate some nerve fibers. Because small fibers in the nerves communicate with blood vessels, injuries to the fibers may trigger the many different symptoms of complex regional pain syndrome. Molecules secreted from the ends of hyperactive small nerve fibers are thought to contribute to inflammation and blood vessel abnormalities. These peripheral nerve abnormalities in turn trigger damage in the spinal cord and brain.

Blood vessels in the affected limb may dilate (open wider) or leak fluid into the surrounding tissue, causing red, swollen skin. The dilation and constriction of small blood vessels is controlled by small nerve fiber axons as well as chemical messengers in the blood. The underlying muscles and deeper tissues can become starved of oxygen and nutrients, which causes muscle and joint pain as well as damage. The blood vessels may over-constrict (clamp down), causing cold, white, or bluish skin.

Complex regional pain syndrome also affects the immune system. High levels of inflammatory chemicals (cytokines) have been found in the tissues of people with complex regional pain syndrome. These contribute to the redness, swelling, and warmth reported by many affected individuals. Complex regional pain syndrome is more common in individuals with other inflammatory and autoimmune conditions such as asthma.

Limited data suggest that complex regional pain syndrome also may be influenced by genetics. Rare family clusters of complex regional pain syndrome have been reported. Familial complex regional pain syndrome may be more severe with earlier onset, greater dystonia, and more than one limb being affected. When comparing patients with sporadic complex regional pain syndrome to families where two or more patients are affected, familial complex regional pain syndrome patients had a younger age at onset and more often had multiple affected extremities and dystonia ¹⁷³. A recent study demonstrated that a single nucleotide polymorphism in four genes, ANO10, P2RX7, PRKAG1, and SLC12A9, is associated with developing complex regional pain syndrome type 1 with males typically expressing these rare alleles ¹⁷⁴. Other genetic studies have demonstrated associations between complex regional pain syndrome and several major histocompatibility complex alleles, including human leukocyte antigen (HLA)-DR6, HLA-DR13, HLA-DR2, HLA-DQ1, HLA-B62, and HLA-DQ8 ¹⁷⁵. Genome-wide expression profiling of the whole blood has shown that HLA-A29.1, matrix metallopeptidase 9 (MMP9), alanyl aminopeptidase (AAP), histidine decarboxylase (HDC), granulocyte colony-stimulating factor 3 receptor (G-CSF3-R), and signal transducer and activator of transcription 3 genes (STAT-3) were highly expressed when compared to unaffected controls ¹⁷⁶. Further genetic and transcriptomic studies hold the promise to predict patient predispositions to complex regional pain syndrome, unravel the molecular mechanisms of complex regional pain syndrome pathogenesis, and discover novel therapeutic targets for complex regional pain syndrome ¹⁷⁷.

Occasionally complex regional pain syndrome develops without any known injury. In these cases, an infection, a blood vessel problem, or entrapment of the nerves may have caused an internal injury. A physician will perform a thorough examination in order to identify a cause.

In many cases, complex regional pain syndrome results from a variety of causes. In such instances, treatments are directed at all of the contributing factors.

Risk factors for developing complex regional pain syndrome

Potential risk factors for developing complex regional pain syndrome ¹⁶⁴:

Female sex, in particular postmenopausal women (women of middle age also sustain fractures three times more often than men)
Severe injuries, in particular crush injuries, displaced, juxta-articular or intra-articular fractures (especially distal radius fractures); ankle injuries; nerve injuries; prolonged anesthesia/ischemia, manipulation procedures such as secondary fracture reductions; restricted range of motion and functional impairment, prolonged immobilization
High pain intensity initially or directly after surgery, sensory disturbances and low skin temperature (for example, persistent pain ≥5 on a numerical rating scale of 10 points for more than a week after conservative treatment of a distal radius fracture)
Chronic or widespread pain and hypersensitivity, such as migraine, fibromyalgia, back/period pain, neuropathies, osteoporosis, osteoarthritis, rheumatoid arthritis; also, asthma/allergies
High anxiety level, depressiveness, passivity, avoidance tendency, pain catastrophizing, or manifest disorders associated with anxiety and trauma/stress; previous critical life events; desire for compensation and litigation.

Extremity injuries, such as fractures or sprains, surgery, and carpal tunnel syndrome have been the most commonly reported inciting events leading to complex regional pain syndrome ¹⁶⁹, ¹⁷¹, ¹⁷⁸. In a recent analysis of 1043 patients with complex regional pain syndrome, the most common primary causes were fractures (42%), blunt traumatic injuries excluding fractures (e.g., sprains) (21%), surgery (12%), and carpal tunnel syndrome (7%), while 7% had no clear precipitating event ¹⁶⁹. However, the overall prevalence of complex regional pain syndrome associated with these inciting events remains relatively low. Crijns et al. ¹⁷⁹ found that out of 59,765 patients treated for distal radius fractures, 0.19% were diagnosed with complex regional pain syndrome. A similar more recent study noted a 0.64% incidence of complex regional pain syndrome after 172,194 patients receiving surgical treatment for distal radius fractures ¹⁷¹. Complex regional pain syndrome had previously been reported as a common complication of Dupuytren contracture, but a very recent analysis of a nationwide database found the overall incidence to be 0.31% ¹⁸⁰.

Multiple studies have demonstrated complex regional pain syndrome to be much more prevalent in women, with estimates of 2–4 times the rate in men ¹⁶⁹, ¹⁷¹, ¹⁸¹, ¹⁸², ¹⁸³. Van Velzen et al. ¹⁸³ further investigated these sex-related differences, finding that male complex regional pain syndrome patients were more likely to suffer from depression and kinesiophobia, and use passive pain coping strategies. Fibromyalgia is strongly and independently associated with a diagnosis of complex regional pain syndrome, increasing the risk up to 2.5 times that of controls ¹⁷⁹, ¹⁸⁴. Other musculoskeletal conditions, such as rheumatoid arthritis, may also increase the risk ¹⁸⁵. Although complex regional pain syndrome and other autonomic disorders have been anecdotally reported as adverse events after human papillomavirus (HPV) vaccination, review of published reports and a small population-based case series found no statistically significant correlation ¹⁸⁶, ¹⁸⁷, ¹⁸⁸.

Complex regional pain syndrome prevention

These steps might help you reduce the risk of developing complex regional pain syndrome:

Taking vitamin C after a wrist fracture. Studies have shown that people who took a daily minimum dose of 500 milligrams (mg) of vitamin C after a wrist fracture had a lower risk of complex regional pain syndrome compared with those who didn’t take vitamin C.
Early mobilization after a stroke. Some research suggests that people who get out of bed and walk around soon after a stroke (early mobilization) lower their risk of complex regional pain syndrome.

Complex regional pain syndrome symptoms

The key symptom of complex regional pain syndrome is prolonged severe pain that may be constant. It has been described as “burning,” “pins and needles” sensation, or as if someone were squeezing the affected limb. The pain may spread to the entire arm or leg, even though the injury might have only involved a finger or toe. In rare cases, pain can sometimes even travel to the opposite extremity. There is often increased sensitivity in the affected area, known as allodynia, in which normal contact with the skin is experienced as very painful.

People with complex regional pain syndrome also experience changes in skin temperature, skin color, or swelling of the affected limb. This is due to abnormal microcirculation caused by damage to the nerves controlling blood flow and temperature. As a result, an affected arm or leg may feel warmer or cooler compared to the opposite limb. The skin on the affected limb may change color, becoming blotchy, blue, purple, pale, or red.

Other common features of Complex regional pain syndrome include:

changes in skin texture on the affected area; it may appear shiny and thin
abnormal sweating pattern in the affected area or surrounding areas
changes in nail and hair growth patterns
stiffness in affected joints
problems coordinating muscle movement, with decreased ability to move the affected body part
abnormal movement in the affected limb, most often fixed abnormal posture (called dystonia), but also tremors in or jerking of the limb.

Complex regional pain syndrome complications

If complex regional pain syndrome isn’t diagnosed and treated early, the disease may progress to more disabling signs and symptoms. These may include:

Tissue wasting (atrophy). If you avoid moving an arm or a leg because of pain or if you have trouble moving a limb because of stiffness, your skin, bones and muscles may begin to deteriorate and weaken.
Muscle tightening (contracture). You also may experience tightening of your muscles. This may lead to a condition in which your hand and fingers or your foot and toes contract into a fixed position.

Complex regional pain syndrome diagnosis

Currently there is no specific test that can confirm complex regional pain syndrome and complex regional pain syndrome remains a clinical diagnosis of exclusion based on the history, symptoms and signs assisted with the application of the Budapest criteria ¹³¹, ¹⁴⁸, ¹²⁸. Complex regional pain syndrome diagnosis is based on a person’s medical history, and signs and symptoms that match the definition. Since other conditions can cause similar symptoms, careful examination is important. As most people improve gradually over time, the diagnosis may be more difficult later in the course of the disorder.

Testing also may be used to help rule out other conditions, such as arthritis, Lyme disease, generalized muscle diseases, a clotted vein, or small fiber polyneuropathies, because these require different treatment. The distinguishing feature of complex regional pain syndrome is that of an injury to the affected area. Such individuals should be carefully assessed so that an alternative treatable disorder is not overlooked.

Magnetic resonance imaging (MRI) or triplephase bone scans may be requested to help confirm a diagnosis. While complex regional pain syndrome is often associated with excess bone resorption, a process in which certain cells break down the bone and release calcium into the blood, this finding may be observed in other illnesses as well.

Bone scan with technetium Tc 99m. This procedure might help find bone changes. A radioactive substance injected into one of your veins allows your bones to be seen with a special camera.
Sympathetic nervous system tests. These tests look for disturbances in your sympathetic nervous system. For example, thermography measures the skin temperature and blood flow of your affected and unaffected limbs. Other tests can measure the amount of sweat on both limbs. Uneven results can indicate complex regional pain syndrome.
- Infrared thermometry or thermography has the highest specificity of any objective test for complex regional pain syndrome ¹⁶². In earlier phases of the disease, the affected limb typically shows higher temperatures compared to the opposite limb ¹⁸⁹. This observation has been shown to reverse with disease progression. Sensitivity for complex regional pain syndrome has been reported as low as 45% ¹⁹⁰. Thermography requires specialized equipment and accuracy depends on the ability to maintain thermoregulation during measurements ¹⁶², ¹⁹¹. The utility of other autonomic function tests including, quantitative sudomotor axon reflex testing and thermoregulatory sweat testing, have similar limitations in that they require specialized equipment, knowledgeable operators, and they have a lower specificity for complex regional pain syndrome ¹⁶², ¹⁹⁰.
X-rays. Loss of minerals from your bones may show up on an X-ray in later stages of the disease. However, X-ray has low reported sensitivity and specificity for complex regional pain syndrome ¹⁹², ¹⁹⁰. X-ray greatest utility is exclusion of other musculoskeletal injuries, particularly in early diagnosis of a unilateral extremity presentation of the disease.
Magnetic resonance imaging (MRI). Images captured by an MRI test may show a number of tissue changes. Magnetic resonance imaging (MRI) is especially useful in the exclusion of musculoskeletal disorders, particularly osteonecrosis ¹⁹⁰. MRI has been shown to be less sensitive for complex regional pain syndrome diagnosis than bone scan in comparative studies ¹⁹³.
Doppler flow studies. Doppler flow studies have been suggested to assess vascular reflexes, especially in patients with symptom duration of four months or less ¹⁶². Doppler flow study can also be used for exclusion of contributing vascular pathologies, particularly venous thrombosis.

Complex regional pain syndrome treatment

There is some evidence that early (within the first few months of symptom onset) aggressive treatment of pain may prevent complex regional pain syndrome symptoms ¹⁹⁴. Currently there are not enough high quality studies to guide clear treatment decisions in complex regional pain syndrome ¹⁹⁵. Clinical guidelines, which represent the available evidence and the views of clinical experts in complex regional pain syndrome suggest a number of treatments that may be helpful ¹⁹⁶. Treatment options include referral for physical and occupational therapy, a short course of oral corticosteroids, bisphosphonates, and transdermal lidocaine patches ¹⁹⁷. Evidence suggests that bisphosphonates used for the first six months of symptoms and a short course (two to four weeks) of oral corticosteroids significantly improve pain in patients with complex regional pain syndrome ¹⁵⁹. Often, a combination of different treatments, tailored to your specific case, is necessary ¹⁹⁸.

The goal of treatment is to improve function and decrease pain. Complex regional pain syndrome is most likely to respond to a comprehensive, integrated, multi-disciplinary treatment approach that involves medical, psychological, and physical and occupational therapy components ¹⁵⁹.

Rehabilitation and physical therapy and occupational therapy

An exercise program to keep the painful limb or body part moving can improve blood flow and lessen the circulatory symptoms ¹⁹⁹. Additionally, exercise can help improve the affected limb’s flexibility, strength, and function. Rehabilitating the affected limb also can help to prevent or reverse the secondary brain changes that are associated with chronic pain. Occupational therapy can help the individual learn new ways to work and perform daily tasks.

The challenge with implementing physical and occupational therapy is the broad range of interventions available to therapists and the persistent lack of understanding regarding the underlying pathophysiology of complex regional pain syndrome ¹²⁸. Regardless, a number of case reports have been published showing efficacy in a wide range of interventions, ranging from strain-counterstrain (SCS), neural mobilization techniques, and thrust manipulation ²⁰⁰, ²⁰¹, ²⁰². These techniques often rely on some form of neuromodulation, either through decrease in proprioceptive hyperactivity as seen in strain-counterstrain (SCS) or activation of descending pain pathways and inhibitory mechanisms in spinal manual therapy. Additionally, there is evidence of analgesic effects achieved through the release of neurotensin and oxytocin, providing patients with short-term analgesia that may subsequently enhance their ability to participate in other therapeutic modalities they may previously not have tolerated ²⁰³, ²⁰⁴. Additionally, there is likely a role involving catecholamines in the pathophysiological pathway of complex regional pain syndrome.

Psychotherapy

Complex regional pain syndrome and other painful and disabling conditions often are associated with profound psychological symptoms for affected individuals and their families. People with complex regional pain syndrome may develop depression, anxiety, or post-traumatic stress disorder, all of which heighten the perception of pain and make rehabilitation efforts more difficult. Treating these secondary conditions is important for helping people cope and recover from complex regional pain syndrome. Furthermore, complex regional pain syndrome patient population carries significant risk factors for suicidal ideation, including: severe pain, depressive symptoms and functional impairment. The link between chronic pain and suicidal ideation has been well established, and given the additional autonomic dysfunction associated with complex regional pain syndrome, these patients carry a significant risk for suicidality ²⁰⁵, ²⁰⁶, ²⁰⁷, ²⁰⁸.

Although the evidence is lacking in clinical trial evidence, case series have shown promise in the benefits of various forms of psychotherapy intervention, especially when combined with other non-invasive modalities ¹²⁸. Additionally, adaptation of the treatment regimen to the evolution of a patient’s symptoms is critical ²⁰⁹. Of particular interest is the study conducted by Fialka et al. ²¹⁰ who found a decrease in limb temperature in the psychotherapy arm compared to the physical therapy only group. Although the study was limited by its lack of power, it lends further support to the role psychological stress can play in the progression of complex regional pain syndrome ²¹¹, ²¹⁰.

Complex regional pain syndrome medications

Several different classes of medication have been reported to be effective in treating complex regional pain syndrome, particularly when used early in the course of the disease. However, no drug is approved by the U.S. Food and Drug Administration specifically for complex regional pain syndrome, and no single drug or combination of drugs is guaranteed to be effective in every person.

Drugs to treat complex regional pain syndrome include:

bisphosphonates, such as high dose alendronate or intravenous pamidronate
non-steroidal anti-inflammatory drugs (NSAIDs) to treat moderate pain, including over-the-counter aspirin, ibuprofen, and naproxin
corticosteroids that treat inflammation/swelling and edema, such as prednisolone and methylprednisolone (used mostly in the early stages of complex regional pain syndrome)
drugs initially developed to treat seizures or depression but now shown to be effective for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, nortriptyline, and duloxetine
botulinum toxin injections
opioids such as oxycontin, morphine, hydrocodone, fentanyl, and Vicodin. These drugs must be prescribed and monitored under close supervision of a physician, as these drugs may be addictive.
N-methyl-D-aspartate (NMDA) receptor antagonists such as dextromethorphan and ketamine, and
topical local anesthetic creams and patches containing numbing agents such as lidocaine.

All drugs or combination of drugs can have various side effects such as drowsiness, dizziness, increased heartbeat, and impaired memory. Inform a healthcare professional of any changes once drug therapy begins.

Non-steroidal anti-inflammatory drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenase-2 (COX-2) inhibitors, preventing the synthesis of prostaglandins. Prostaglandins are inflammatory mediators and induce hyperalgesia; therefore, downregulating these molecules may disrupt the process of spinal transmission of nociceptive signals and reduce the acute-pain stage of complex regional pain syndrome ²¹². However, the evidence remains poor regarding the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) although there are case reports showing potential benefits ²¹³, ²¹⁴.

Steroids

Steroids are used to target the inflammatory component of the proposed complex regional pain syndrome pathophysiology mechanism. There have been several studies assessing the efficacy of steroids, at various doses, various time-intervals and in patients with varying degrees of complex regional pain syndrome duration (acute vs chronic) ²¹⁵, ²¹⁶, ²¹⁷. Given the noteworthy and potentially significant side effects associated with prolonged steroid use, care needs to be exercised by the clinician when considering these medications. One trial in particular was notable for the significant benefits of a tapered prednisone regimen in patients with an average duration of 1.9 months since onset of complex regional pain syndrome in reducing Visual Analogue Scale (VAS) pain scores ²¹⁸.

Gabapentin

Gabapentin, originally used as a muscle relaxer and anti-spasmodic medication, has been found to be an effective adjunct anticonvulsant with neural pain control potential ²¹⁹. Van de Vusse et al. ²²⁰ performed a randomized double blind placebo controlled crossover study and found that while gabapentin only had a mild effect on pain in complex regional pain syndrome 1, it had a significant impact on reducing the sensory deficit in the affected limb. These results were similar in the pediatric population, as Brown et al. ²²¹ found that gabapentin significantly reduced pain intensity scores while improving sleep. This study found that both the antidepressant amitriptyline and the anticonvulsant gabapentin were analogous in their effectiveness in reducing pain in complex regional pain syndrome 1. A limitation of these trials was the low number of participants in the trials. While commonly utilized in the treatment of complex regional pain syndrome, there are ultimately few randomized control trials with solid evidence to prove the efficacy of gabapentin, suggesting that there needs to be further research into gabapentin with respect to complex regional pain syndrome ¹⁹⁹.

Bisphosphonates

Bisphosphonates inhibit osteoclastic bone resorption by to hydroxyapatite sites, especially at sites undergoing active bone resorption. The exact mechanism for how bisphosphonates provide pain relieve in complex regional pain syndrome remains unclear, although there are a number of potential mechanisms that have been proposed and the true mechanism is likely multifactorial in nature given the limited degree of bone turnover noted in complex regional pain syndrome ²²². Regardless, there appears to be a degree of evidence indicating the benefit of bisphosphonates in reducing pain scores in comparison to placebo; however, many of the early trials were often lacking in power. In addition, a lack of true understanding behind the mechanism of action for therapeutic benefit with bisphosphonates limits the ability to identify ideal drug and dosing regimens ²²³, ¹⁹⁹. However, a randomized, double-blind, placebo-controlled study comparing four doses of intravenous (IV) neridronate to placebo found statistically significant decreases in Visual Analogue Scale (VAS) pain scores in the study of 82 patients. The authors posit that these results may be linked to bisphosphonate reduction of the increased bone turnover and subsequent marrow edema seen in complex regional pain syndrome that may contribute to chronic pain. Additionally, locally accumulated drug may interfere with the inflammatory pathways and subsequent pain generation by decreasing lactate concentration and acidosis. Interestingly, some patients also experienced permanent remission of their disease; however, it should be noted that these patients were identified early in their clinical course, an important caveat to the efficacy of bisphosphonates in treating complex regional pain syndrome. Regardless, the significant efficacy and limited adverse effects of the medications suggest an importance in incorporation of bisphosphonates as standard of care when initiating treatment for complex regional pain syndrome patients ²²².

Ketamine

Ketamine is a strong anesthetic with an N-methyl-D-aspartate (NMDA) receptor antagonist has a notable role in the modulation of the wind-up response to noxious stimuli that results in central sensitization classically seen in chronic pain conditions. There is also evidence of a role in immunomodulation resulting in the down-regulation of neuroinflammatory markers; therefore, it remains unclear if the potential role of ketamine in complex regional pain syndrome treatment is relegated solely to the effects of NMDA antagonism resulting in down-regulation of central sensitization or if there are additional factors involved ²²⁴, ²²⁵. Investigators are using low doses of ketamine given intravenously for several days to either reduce substantially or eliminate the chronic pain of complex regional pain syndrome. In certain clinical settings, ketamine has been shown to be useful in treating pain that does not respond well to other treatments. Regardless, the current body of evidence is lacking in supporting the efficacy of ketamine in the treatment of complex regional pain syndrome with the majority of studies lacking in power or utilizing different modes of administration, making it difficult to determine the level of evidence supporting ketamine ²²⁶, ²²⁷, ²²⁴.

Botulinum Toxin A

The use of Botulinum Toxins A and B have been an emerging add-on (adjunct) to local anesthetics for sympathectomies and treatment of dystonia or spasticity in the treatment of complex regional pain syndrome, with most studies published starting in 2008. The mechanism of this therapy was hypothesized to be slightly different depending on the use for treating dystonia and spasticity or for a sympathectomy. In dystonia, the role of botulinum toxin in therapy is due to its function in disrupting the SNARE complex and inhibition of exocytosis. It prevents the release of acetylcholine and causes flaccid paralysis, effectively relieving the pain from muscle dystonia and spastic contractility ²²⁸, ²²⁹. A retrospective case review of the use of Botulinum Toxin A (Botox) in patients with neck or upper limb girdle muscles with dystonia and spasm showed that there was significant pain relief in 97% of the patients over the first 4 weeks after treatment. Given the efficacy of botulinum toxin in inhibition of cholinergic circuitry, several studies have expanded its use to blocking cholinergic signaling at the sympathetic ganglia in complex regional pain syndrome patients. The majority of studies have been small case-control or retrospective studies regarding the efficacy of Botulinum Toxin A (Botox) and Botulinum Toxin B (BTX-B), either by themselves or in conjunction with local anesthetic. While these studies range from retrospective studies to prospective randomized controlled trials, they all show moderate improvements in pain scores over the short term with either botulinum toxin alone or with local anesthetic. They also reliably show that the use of botulinum toxin has a greater duration of efficacy than the use of local anesthetic alone ²³⁰. A meta-analysis performed in 2020 which evaluated randomized controlled trials provided good evidence for the efficacy of Botulinum Toxin A (Botox) for pain relief across neuropathic and muscle based pain syndromes ²³¹. There are numerous other studies that suggest the use of Botulinum Toxin A (Botox) and Botulinum Toxin B (BTX-B) depending on the location of the sympathectomy, but there is not yet strong evidence for the use of one or the other purely based on the site of complex regional pain syndrome being treated ²³², ²³³. There is currently a study underway with very similar parameters looking at the impact to quality of life and disability scores in complex regional pain syndrome patients ²³⁴. While Botulinum Toxin A (Botox) has significant therapeutic potential, there are concerns about possible extravasation into surrounding ganglia which could lead to neurologic complications as well as discrepancies between industry and non-industry-sponsored studies ²³⁵.

Antioxidants

In the search for improved pharmacological treatments for complex regional pain syndrome, the use of antioxidants has been increasingly studied over the past ten years, spanning the fields of rheumatology, anesthesiology and orthopedics. This is primarily regarding complex regional pain syndrome Type 1, with an established injury or trauma, in many cases from surgery. Eisenberg et al. ²³⁶ in 2008 demonstrated that when comparing complex regional pain syndrome 1 and control patients, the patients with complex regional pain syndrome had significantly elevated salivary peroxidase, superoxide dismutase activity, uric acid and total antioxidant status compared to controls. In 2014 Baykal et al. ²³⁷ had similar findings, showing that superoxide dismutase, glutathione peroxidase and glutathione s-transferase activity were all significantly elevated in patients who developed complex regional pain syndrome Type 1 when compared to patients who did not. Several studies have been done regarding the prophylactic treatment of surgical patients with Vitamin C post-operatively. These have found that prophylaxis with 500 mg to 1 g of Vitamin C daily post operatively from total knee arthroplasty, foot and ankle surgery, and subacromial shoulder surgery had a statistically significant effect on the development of complex regional pain syndrome 1 ²³⁸, ²³⁹, ²⁴⁰. Patients who received Vitamin C were less likely to develop complex regional pain syndrome, considered to be through the role of Vitamin C in stabilizing reactive oxygen species and in turn reducing inflammation. A meta-analysis of randomized controlled trials using vitamin C for complex regional pain syndrome prophylaxis found a similar reduction in the risk of complex regional pain syndrome development ²⁴¹. In all, it is safe to say that Vitamin C perioperatively could be a valuable tool in the prevention of complex regional pain syndrome Type 1, especially in the elective surgical setting, ultimately reducing the incidence of this often-debilitating disease.

Sympathetic nerve block

Some individuals report temporary pain relief from sympathetic nerve blocks, but there is no published evidence of long-term benefit. Sympathetic blocks involve injecting an anesthetic next to the spine to directly block the activity of sympathetic nerves and improve blood flow.

It is thought that one of the underlying pathophysiologic mechanisms of complex regional pain syndrome is sympathetic hyperactivity. The most common sympathetic blocks for complex regional pain syndrome are the stellate ganglion sympathetic blocks used to treat upper extremity symptoms while lumbar sympathetic nerve blocks are used to treat lower extremity symptoms ¹⁴⁸. Although the quality of the evidence was low, a 2013 Cochrane review found that sympathetic blocks combined with local anesthetic were ineffective at reducing complex regional pain syndrome-related pain ²⁴². A more recent Cochrane review in 2016 was unable to make any firm judgments regarding the effectiveness of this type of treatment for complex regional pain syndrome ²⁴². In 2019 a study looked at the relationship between sympathetic blocks and spinal cord stimulation and found that the effects of a sympathetic block did not predict the success of a spinal cord stimulator ²⁴³.

Surgical sympathectomy

A surgical sympathectomy is a procedure that cuts or clamps the sympathetic nerve chain to treat conditions such as excessive sweating, facial blushing, some chronic pain conditions, and Raynaud phenomenon. A surgeon cuts or clamps the sympathetic nerve chain, which runs along the spine in the chest and controls the body’s fight-or-flight response. Sympathectomy is a last resort when other treatments, such as medicines or antiperspirants, have not worked. The use of this operation that destroys some of the nerves is controversial. Some experts think it is unwarranted and makes complex regional pain syndrome worse, whereas others report a favorable outcome. Sympathectomy should be used only in individuals whose pain is dramatically relieved (although temporarily) by sympathetic nerve blocks.

Spinal cord stimulation

Placing stimulating electrodes through a needle into the epidural space to deliver electric stimulation to the spinal cord’s dorsal column provides a tingling sensation in the painful area. Electrodes may be placed temporarily for a few days in order to assess whether spinal cord stimulation (SCS) is likely to be helpful. Minor surgery is required to implant all the parts of the stimulator, battery, and electrodes under the skin on the torso. Some spinal cord stimulation (SCS) devices use an external pulse generator, but typically the electrodes are connected to an implanted pulse generator. Several mechanisms of action for spinal cord stimulation (SCS) have been proposed, including vasodilation, reversal of cortical maladaptive neuroplastic changes, adrenergic inhibition, and inhibition of nociceptive neural conduction in the spinal cord. A comprehensive outcome specific review of the use of spinal cord stimulation specifically for complex regional pain syndrome was published in 2017 ²⁴⁴. High-level evidence continues to support spinal cord stimulation (SCS) beneficial and successful role in the treatment of complex regional pain syndrome patients’ perceived pain relief, pain score, and quality of life ²⁴⁴. Functional improvements were noted with less evidence for complex regional pain syndrome resolution, sleep hygiene improvement, positive psychological impact, and analgesic sparing effects ²⁴⁴. A 2021 study looking at the long-term outcome of spinal cord stimulation (SCS) in complex regional pain syndrome did not find statistical functional improvement or a reduction in opioid or neuropathic pain medication use ²⁴⁵. However, they did note that 70% of the patients continued to use their spinal cord stimulation (SCS) devices at the eight-year follow-up ²⁴⁵. Approximately 25 percent of individuals develop equipment problems that may require additional surgeries.

Dorsal root ganglion stimulation

The dorsal root ganglion serves as an ideal target given its role in processing and transmitting sensory information from the periphery to the central nervous system. In animal models of chronic pain, pathophysiologic changes in the dorsal root ganglion have been noted, including altered expression of various genes that may play a role in the hyperexcitability of neurons involved in the nociceptive pathway. An innovative neuromodulation technique for the treatment of chronic pain targets the dorsal root ganglion (DRG) rather than the spinal cord. The exact mechanism of how dorsal root ganglion stimulation exerts its beneficial effects remains unknown, although it may be related to the modulation of a variety of cells housed within the The dorsal root ganglion serves as an ideal target given its role in processing and transmitting sensory information from the periphery to the central nervous system. In animal models of chronic pain, pathophysiologic changes in the dorsal root ganglion have been noted, including altered expression of various genes that may play a role in the hyperexcitability of neurons involved in the nociceptive pathway ²⁴⁶, ²⁴⁷, ²⁴⁸, ²⁴⁹.

As opposed to conventional spinal cord stimulation (SCS), dorsal root ganglion stimulation enables a more targeted application of neurostimulation due to the dorsal root ganglion’s more peripheral location and ease of access. For the treatment of lower extremity pain in complex regional pain syndrome, dorsal root ganglion stimulation received approval from the US Food and Drug Administration (FDA) in 2016. According to a recent pooled analysis study, dorsal root ganglion stimulation was safe and effective for complex regional pain syndrome, resulting in a 4.9-point mean decrease in complex regional pain syndrome type 1 pain intensity ²⁵⁰. In 2017 the ACCURATE study compared spinal cord stimulation (SCS) and dorsal root ganglion stimulation in 152 patients with complex regional pain syndrome ²⁴⁸. Dorsal root ganglion stimulation was found to be more efficient than conventional spinal cord stimulation (SCS) in this multicenter randomized trial for reducing pain and enhancing quality of life in complex regional pain syndrome patients ²⁴⁸.

Other types of neural stimulation

Neurostimulation can be delivered at other locations along the pain pathway, not only at the spinal cord. These include near injured nerves (peripheral nerve stimulators), outside the membranes of the brain (motor cortex stimulation with dural electrodes), and within the parts of the brain that control pain (deep brain stimulation). A recent option involves the use of magnetic currents applied externally to the brain (known as repetitive Transcranial Magnetic Stimulation, or rTMS). A similar method that uses transcranial direct electrical stimulation is also being investigated. These stimulation methods have the advantage of being non-invasive, with the disadvantage that repeated treatment sessions are needed.

Epidural infusion

Epidural infusion is an alternative therapy to provide pain control, by allowing one to vary local anesthetic concentration and infusion dose to be titrated to the desired effect ¹³¹. Adjuvant (add-on) medications, such as clonidine with the addition of opioids, can be added to provide additional spinal analgesia and to potentiate the degree of relief ¹³¹. The most commonly used combination of epidural medications today includes clonidine with bupivacaine ¹³¹. Opioids can be added to the mixture if the pain relief is inadequate or if the local anesthetic concentration required to produce pain relief also prohibits ambulation or full participation in the physiotherapy program ¹³¹.

The primary benefit of continuous regional analgesia is that one is able to effectively titrate to the necessary degree of relief and promote active physical therapy as tolerated ¹³¹. Furthermore, with patient-activated bolus programming, these continuous regional techniques allow patients to self-administer small boluses for optimal analgesia as the pain levels fluctuate ¹³¹. Either before or after a strenuous exercise program, patients may experience elevations in pain, swelling, or allodynia. The ability for patients to readily self-administer extra doses of medication within certain pre-programmed parameters will improve patient satisfaction and optimize pain control ¹³¹. Rauck et al. ²⁵¹ performed a randomized, blinded, placebo-controlled trial utilizing epidural clonidine. They randomized 26 patients with complex regional pain syndrome to receive daily epidural infusions (for 3 consecutive days) of clonidine 300 or 600 mcg, or placebo ²⁵¹ If patients responded to the clonidine with analgesia and did not respond to placebo, they were placed on an open label infusion for a mean of 32 days at a mean dose of 32 mcg/hour ²⁵¹. All patients had substantial relief with both the 300 and 700 microgram doses. Of the 26 patients, 19 elected to receive continuous infusions of clonidine for an average of 43 days with an average dose 32 ± 6 micrograms per hour ²⁵¹. Seventeen of nineteen patients had statistically significant improvement in pain. Side effects were dizziness, dry mouth, mouth sores, and nausea. Six of 19 patients developed catheter related infection, and one developed meningitis ²⁵¹.

Cooper et al. ²⁵² studied 14 patients in a prospective open label trial and demonstrated improved pain relief and range of motion in patients receiving an epidural bupivacaine-opioid mixture for an average of 4 days. Thirteen of fourteen patients had significant improvement, with 11 of the 14 achieving “resolution of their complex regional pain syndrome” by the end of the trial with no activity restrictions ²⁵². Konig et al. ²⁵³ studied 26 patients by using continuous cervical epidural analgesia of bupivacaine (0.25%) for seven days coupled with physical therapy. Eighty-three percent of patients had “improvement in pain”. Edema, sweating abnormalities, and dysfunction of the hand responded particularly well. Sixty-three percent of patients considered their condition to be acceptable whereas only 8% were completely pain free. Reduction in pain medications usage was also noted. Finally, Bucheit and Crews ²⁵⁴ described a single case report where continuous epidural infusion markedly improved range of motion.

The reported rates of infection in epidural catheters used to treat complex regional pain syndrome are as high as 31% ²⁵¹. Therefore, epidural catheters meant for longer-term use should be performed as minor surgical procedures that require standard surgical sterility techniques. Catheters should be tunneled under the skin and away from the midline entrance point to the spine to minimize the colonization by bacteria that is inherently a greater risk with extended duration infusions. Standard catheter dressings, such as those required for extended central venous catheters, should be followed and dressings should be changed weekly. The hallmarks of an epidural abscess include the triad of back pain, sensorimotor loss, and loss of bowel and bladder function. Epidural abscesses may have earlier prodromal symptoms such as fever, neck pain, or photophobia ²⁵⁵. Careful attention to early symptoms is paramount for early diagnosis. A previous study has demonstrated a catheter related infection rate of 19 out of 350 patients. All of these patients were treated with antibiotics and catheter removal, and none required surgical intervention ²⁵⁵.

Intrathecal drug pumps

An intrathecal drug pump, also known as a pain pump, is a surgically implanted device that delivers painrelieving medications directly into the spinal fluid to treat chronic pain and spasticity. These medication may include opioids, local anesthetic agents, clonidine, and baclofen. The pump is about the size of a hockey puck and is implanted under the skin in the abdomen, flank, or axilla. A catheter is then inserted into the spinal cord and connected to the pump. Intrathecal pumps are often used to treat chronic pain caused by conditions such as cancer, neuropathic pain, failed back surgery, cerebral palsy, multiple sclerosis, stroke, brain injury, and spinal cord injury. Intrathecal pumps can provide more effective pain relief with fewer side effects than oral medication.

Intrathecal analgesia has been studied to a lesser extent when compared to epidural analgesia. Lundborg ²⁵⁶ reported a series of three patients with refractory complex regional pain syndrome, who did not have a favorable clinical response to intrathecal bupivacaine. In spite of initial analgesia, all patients demonstrated a progression of their complex regional pain syndrome ²⁵⁶. In a small subset of patients (n = 7) with refractory complex regional pain syndrome and severe dystonia, van Hilten et al. ²⁵⁷ demonstrated analgesia and functional restoration after a bolus of intrathecal baclofen injected in a double-blind fashion followed by intrathecal infusion. But van Hilten et al ²⁵⁷ stopped using intrathecal baclofen infusions due to what they deemed as unacceptable side effects. Intrathecal infusion for complex regional pain syndrome without dystonia has only limited supporting literature ²⁵⁷.

The major risk associated with these infusion techniques is the rate of infection, which remains to be defined by further prospective study on infusion techniques in complex regional pain syndrome patients.

Topical Treatments

Topical treatments must be distinguished from transdermal formulations such as the fentanyl or clonidine patches that deliver systemic medication through the skin. Topical medications remain local, reaching dermal nerve endings, blood vessels, and other cells in the skin. Topical medications are appealing by virtue of their relative lack of systemic effects; rashes and allergies are their only major adverse effect. Topical options to consider for complex regional pain syndrome include the 5% lidocaine impregnated patch, the capsaicin and dimethylsulfoxide (DMSO ¹³¹.

Some clinicians endorse the use Eutectic Mixture of Local Anesthetics (EMLA) for patients with complex regional pain syndrome ²⁵⁸, but it must be applied under an occlusive cover (e.g., plastic food wrap) to maximize penetration. The 5% lidocaine patch is FDA-approved for treating postherpetic neuralgia (PHN), and is available in generic formulation ²⁵⁹. It may have efficacy in some local or focal complex regional pain syndrome phenomena such as allodynia ²⁶⁰.

Capsaicin, the vanilloid compound in chili peppers, is a highly selective agonist for the Transient Receptor Potential channel, Vanilloid-receptor type 1 (TRPV1) that is expressed on central and peripheral terminals of nociceptive primary sensory neurons ²⁶¹. Topical capsaicin causes activation followed by dying-back of nociceptive nerve endings by allowing unchecked cation influx ²⁶¹. Capsaicin use is limited by the painful burning sensation it evokes at the site of application until the site becomes denervated. In a randomized controlled trial, topical capsaicin showed modest efficacy for post herpetic neuralgia ²⁶². A preliminary study of high-dose topical capsaicin plus regional anesthesia for complex regional pain syndrome demonstrated partial efficacy ²⁶³. Some doctors have found topical capsaicin to be intolerably painful, somewhat messy, and unacceptable to most patients ²⁶⁴, ²⁶⁵, ²⁶⁶, ²⁶⁷, ²⁶⁸. In 2009, the FDA approved a high concentration 8% capsaicin patch for treating post herpetic neuralgia once every 3 months ²⁶⁹. Capsaicin is applied to the painful area for 1 hour after topical local anesthesia. Two additional well-powered randomized controlled trials were positive for high-versus low-dose capsaicin in peripheral neuropathic pain, including in HIV-associated distal sensory polyneuropathy ²⁷⁰, ²⁷¹. However, in complex regional pain syndrome, exacerbated pain may render this treatment unsuitable ²⁷².

Dimethyl sulfoxide (DMSO) is a free radical-scavenging agent. In a systematic review DMSO (50% cream for 2 months) provided significant complex regional pain syndrome symptom reduction when compared with placebo ²⁷³, however pain intensity was not improved ²⁷⁴.

Emerging treatments

Emerging treatments for complex regional pain syndrome include:

Intravenous immunoglobulin (IVIG)

Researchers in United Kingdom report low-dose IVIG reduced pain intensity in a small trial of 13 patients with complex regional pain syndrome for 6 to 30 months who did not respond well to other treatments. Those who received intravenous immunoglobulin (IVIG) had a greater decrease in pain scores than those receiving saline during the following 14 days after infusion.

A randomized controlled trial of low-dose (0.5 g/kg) intravenous immunoglobulin (IVIG) treatment for persistent complex regional pain syndrome indicated efficacy ²⁷⁵. However, a subsequent larger trial was negative ²⁷⁶. Although there is some anecdotal evidence for the efficacy of high-dose IVIG this has not been formally tested.

Plasma exchange therapy

Plasma exchange has been reported effective in several case series ²⁷⁷ and consequently complex regional pain syndrome has been added to the list of possible indications by the international plasma exchange society (ASFA) ²⁷⁸. Plasma exchange treatment, although providing pain improvement in some cases, requires use of long repeat-exchange cycles (e.g., eight exchange treatments over 4 weeks) and is unfortunately complicated regularly by pain increase at the venous access site.

Graded Motor imagery

Several studies have demonstrated the benefits of graded motor imagery therapy for complex regional pain syndrome pain. Individuals do mental exercises including identifying left and right painful body parts while looking into a mirror and visualizing moving those painful body parts without actually moving them.

Several alternative therapies have been used to treat other painful conditions. Options include behavior modification, acupuncture, relaxation techniques (such as biofeedback, progressive muscle relaxation, and guided motion therapy), and chiropractic treatment.

Amputation

The role of amputation in chronic complex regional pain syndrome type 1 is a potentially viable one, specifically for those patients who suffer from intractable and refractory symptoms despite numerous multi-modal therapeutic interventions ¹²⁸. Although not without their own risks as well as the potential for recurrence of complex regional pain syndrome in the remaining limb or other limbs, several studies have noted patient satisfaction with the benefits of amputation ¹²⁸. These retrospective reviews are relatively limited in power; however, they suggest a potential role of amputation for those patients who have exhausted alternative options ²⁷⁹, ²⁸⁰, ²⁸¹. There may be additional benefit in selecting potential amputation candidates for their resilience, as a study conducted by Bodde et al. ²⁰⁷ found that patients with higher resilience scores correlated with higher quality of life and lower psychological distress status post limb amputation. Regardless of the potential benefits, the decision to pursue amputation should be taken in the context of the patient overall, recognizing and acknowledging the associated complications of amputation as well as the risk for minimal relief to recurrence of complex regional pain syndrome ¹²⁸.

Living with complex regional pain syndrome

With early treatment, you may keep complex regional pain syndrome from getting worse. Sometimes the condition improves. If treatment is started early enough, the symptoms may completely go away. People with long-lasting, more severe symptoms often don’t respond to treatment. These people may benefit from a pain management program aimed specifically at dealing with chronic pain.

Take care of your physical and mental health by following these suggestions:

Maintain normal daily activities as best you can.
Pace yourself and be sure to get the rest that you need.
Stay connected with friends and family.
Continue to pursue hobbies that you enjoy and are able to do.

If complex regional pain syndrome makes it difficult for you to do things you enjoy, ask your doctor about ways to get around the obstacles.

Keep in mind that your physical health can directly affect your mental health. Denial, anger and frustration are common with chronic illnesses.

At times, you may need more tools to deal with your emotions. A therapist, behavioral psychologist or other professional may be able to help you put things in perspective. They also may be able to teach you coping skills, such as relaxation or meditation techniques.

Sometimes joining a support group, where you can share experiences and feelings with other people, is a good approach. Ask your doctor what support groups are available in your community.

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Spinal cord stimulator

Spinal cord stimulator

Spinal cord stimulator types

What is spinal cord stimulation used for?

Who should get a spinal cord stimulator?

Why Spinal cord stimulation Procedure is Performed?

Spinal cord stimulator contraindications

Spinal Cord Stimulator Surgery

Spinal cord stimulator trial

Spinal Cord Stimulator Implantation

After the Procedure

Spinal cord stimulator complications

What is Chronic Pain?

Table 1. Chronic Pain Classification (11th version of the International Classification of Diseases (ICD-11))

Chronic pain causes

Chronic pain symptoms

Chronic pain diagnosis

Imaging studies

Chronic pain treatment

Table 2. Chronic Pain Treatment Options

Regular exercise

Diet and Weight Management

Complementary medicine

Table 3. Herbal Supplements used in Chronic Pain

Chronic pain medications

Table 4. Chronic pain medications

Managing your chronic back pain

Pain Relievers and Medicines

Rely on Friends and Family

Establish Life Routines

What is Complex Regional Pain Syndrome?

Complex regional pain syndrome causes

Risk factors for developing complex regional pain syndrome

Complex regional pain syndrome prevention

Complex regional pain syndrome symptoms

Complex regional pain syndrome complications

Complex regional pain syndrome diagnosis

Complex regional pain syndrome treatment

Rehabilitation and physical therapy and occupational therapy

Psychotherapy

Complex regional pain syndrome medications

Non-steroidal anti-inflammatory drugs (NSAIDs)

Steroids

Gabapentin

Bisphosphonates

Ketamine

Botulinum Toxin A

Antioxidants

Sympathetic nerve block

Surgical sympathectomy

Spinal cord stimulation

Dorsal root ganglion stimulation

Other types of neural stimulation

Epidural infusion

Intrathecal drug pumps

Topical Treatments

Emerging treatments

Amputation

Living with complex regional pain syndrome

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