What is complex regional pain syndrome

Complex regional pain syndrome is a chronic (lasting greater than six months) pain condition that most often affects one limb (arm, leg, hand, or foot) usually after an injury, a surgery, a stroke or a heart attack ¹⁾. The pain is out of proportion to the severity of the initial injury. 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 is believed to be caused by damage to or malfunction of, the peripheral and central nervous systems.

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.

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:

• 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. 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 ²⁾. 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 ³⁾; and alterations in body perception or schema ⁴⁾.

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.

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 three of the four following categories Sensory: reports of hyperaesthesia and/or allodynia Vasomotor: reports of temperature asymmetry and/or skin colour changes and/or skin colour asymmetry Sudomotor/oedema: reports of oedema and/or sweating changes and/or sweating asymmetry Motor/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 colour changes and/or asymmetry Sudomotor/oedema: evidence of oedema and/or sweating changes and/or sweating asymmetry Motor/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 ⁵⁾]

Complex regional pain syndrome type 1 (Sudeck’s atrophy or Reflex sympathetic dystrophy)

Reflex sympathetic dystrophy syndrome or Sudeck’s atrophy involves a disturbance in the sympathetic nervous system. The latter is the the network of nerves that controls many bodily functions and in the skin it is responsible for opening and closing blood vessels, and controlling sweat glands. In complex regional pain syndrome type 1 there is pain, as well as swelling and disability (often after injury) associated with other signs of sympatethic nerve dysfunction (initially warm and dry, and later cold and moist skin) in the affected area. It primarily affects the hands and feet.

Complex regional pain syndrome type 1 (Sudeck’s atrophy) is reasonably common – it may occur after as many as 5% of traumatic injuries. Complex regional pain syndrome type 1 frequently occurs between the ages of 40 and 60 but also can occur in children and the elderly. Complex regional pain syndrome type 1 is more common among women.

• The condition may follow weeks or months after the initial cause – whether it be trauma, myocardial infarct or other.
• It classically is said to go through 3 stages
• Early on there is throbbing, burning pain with the site red, warm and swollen;
• After weeks or months the overlying skin may become cold, mottled, and shiny with stiffness and often underlying osteoporosis.
• Later the pain continues, with associated muscle atrophy and there may also be contractures.

Risk Factors for Complex regional pain syndrome 1 (Sudeck’s atrophy, Reflex sympathetic dystrophy)

• It may occur spontaneously (i.e. without any cause) -but more commonly it follows trauma (fractures, ligament and muscle strains, nerve or soft tissue injuries) which may seem trivial.
• It is believed to be due to prolonged immobilization following the injury.
• It can also be associated with medical conditions – diabetes, stroke/heart attack, thyroid disease, cancer, infections.

Complex regional pain syndrome type 2 (Causalgia)

Complex regional pain syndrome type 2 (causalgia) is a chronic pain condition seen after the section (damage, cutting) of a nerve. It is characterized by a chronic burning pain and hypersensitivity in the area supplied by that nerve.

The sympathetic nerve supply of the involved area is believed to be important in the cause of complex regional pain syndrome type 2 (causalgia). The sympathetic nervous system is a network of nerves (separate from the set of nerves controlling voluntary activities) which controls a lot of bodily functions (like our heart rate, intestinal activity) as well as being important in pain perception and skin blood supply.

• Complex regional pain syndrome type 2 most commonly follows trauma.
• Complex regional pain syndrome type 2 is seen occasionally following amputation.

In the majority of people onset of the pain is within 24 hours of injury.

This condition is most common in people between the ages of 40-60, but has been seen in younger people also.

Medical therapy is usually ineffective.

Sympathetic block: 18-25% of patients have satisfactory long-lasting relief after a series of nerve blocks using a local anesthetic injection.

Surgical sympathectomy: This involves cutting the sympathetic nerves to that area of the body, and it relieves pain in more than 90% of patients. Sympathectomy has been reported to provide complete relief in over 80% and significant relief in 95% of patients with causalgia. The risk of significant complication is approximately 5%. These include a pneumothorax (punctured lung), intercostal nerve pain, spinal cord injury, and Horner’s syndrome (droopy eyelid due to nerve damage).

Complex regional pain syndrome prognosis

The outcome of Complex regional pain syndrome is highly variable. Younger persons, children, and teenagers tend to have better outcomes. While older people can have good outcomes, there are some individuals who experience severe pain and disability despite treatment. Anecdotal evidence suggests early treatment, particularly rehabilitation, is helpful in limiting the disorder, a concept that has not yet been proven in clinical studies. More research is needed to understand the causes of complex regional pain syndrome, how it progresses, and the role of early treatment.

Complex regional pain syndrome pictures

Figure 1. Acute complex regional pain syndrome with hyperemia, swelling and glossy skin 

Figure 2. Complex regional pain syndrome – chronic, cold type complex regional pain syndrome with blue discoloration of the fingers, glossy skin, and increased hair and nail growth.

Figure 3. Complex regional pain syndrome – related dystonia of the left ankle and foot with plantar flexion and inversion of the ankle, and flexion of the toes; edema and increased hair growth are also clearly visible.

Complex regional pain syndrome stages

The staging of complex regional pain syndrome is a concept that is no longer used in clinical practice. The course of the disease seems to be so unpredictable between various patients that staging is NOT helpful in the diagnosis and treatment of complex regional pain syndrome. The following stages are presented in these guidelines merely for historical significance.

Stage 1

• Onset of severe, pain limited to the site of injury
• Increased sensitivity of skin to touch and light pressure (hyperasthesia).
• Localized swelling
• Muscle cramps
• Stiffness and limited mobility
• At onset, skin is usually warm, red and dry and then it may change to a blue (cyanotic) in appearance and become cold and sweaty.
• Increased sweating (hyperhydrosis).
• In mild cases this stage lasts a few weeks, then subsides spontaneously or responds rapidly to treatment.

Stage 2

• Pain becomes even more severe and more diffuse
• Swelling tends to spread and it may change from a soft to hard (brawny) type
• Hair may become coarse then scant, nails may grow faster then grow slower and become brittle, cracked and heavily grooved
• Spotty wasting of bone (osteoporosis) occurs early but may become severe and diffuse
• Muscle wasting begins

Stage 3

• Marked wasting of tissue (atrophic) eventually become irreversible.
• For many patients the pain becomes intractable and may involve the entire limb.
• A small percentage of patients have developed generalized complex regional pain syndrome affecting the entire body.

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). Your skin, bones and muscles may begin to deteriorate and weaken if you avoid or have trouble moving an arm or a leg because of pain or stiffness.
• 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 causes

It is unclear why some individuals develop complex regional pain syndrome while others with similar trauma do not. In more than 90 percent of cases, the condition is triggered by a clear history of trauma or injury. 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. 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.

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.

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 diagnosis

Currently there is no specific test that can confirm complex regional pain syndrome. 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. 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.
• X-rays. Loss of minerals from your bones may show up on an X-ray in later stages of the disease.
• Magnetic resonance imaging (MRI). Images captured by an MRI test may show a number of tissue changes.

Complex regional pain syndrome treatment

There’s some evidence that early treatment, within the first few months of symptoms, might help improve complex regional pain syndrome symptoms. Currently there are not enough high quality studies to guide clear treatment decisions in complex regional pain syndrome ⁶⁾. Clinical guidelines, which represent the available evidence and the views of clinical experts in complex regional pain syndrome ⁷⁾ suggest a number of treatments that may be helpful. Often, a combination of different treatments, tailored to your specific case, is necessary.

The following therapies are often used:

Rehabilitation and physical therapy

An exercise program to keep the painful limb or body part moving can improve blood flow and lessen the circulatory symptoms. 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.

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.

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 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.

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.

Surgical sympathectomy

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 spine near the spinal cord provides a tingling sensation in the painful area. Electrodes may be placed temporarily for a few days in order to assess whether stimulation 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. Once implanted, the stimulator can be turned on and off, and adjusted using an external controller. Approximately 25 percent of individuals develop equipment problems that may require additional surgeries.

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.

Intrathecal drug pumps

These devices pump painrelieving medications directly into the fluid that bathes the spinal cord. These medication may include opioids, local anesthetic agents, clonidine, and baclofen. The advantage is that pain-signaling targets in the spinal cord can be reached using doses far lower than those required for oral
administration, which decreases side effects and increases drug effectiveness. There are no studies that show benefit specifically for complex regional pain syndrome.

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.

• Ketamine

Investigators are using low doses of ketamine — a strong anesthetic, 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.

• 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.

Coping and support

Living with a chronic, painful condition can be challenging, especially when — as is often the case with complex regional pain syndrome — your friends and family don’t believe you could be feeling as much pain as you describe. Share information from reliable sources about complex regional pain syndrome with those close to you to help them understand what you’re experiencing.

Follow these suggestions to take care of your physical and mental health:

• 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. He or she may also 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.