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” ¹, ², ³, ⁴, ⁵, ⁶, ⁷, ⁸, ¹, ⁹. The International Association for the Study of Pain (IASP) defines “chronic pain” as persistent or recurrent pain lasting longer than 3 months ¹, ². 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 ¹⁰. 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 ¹¹.

• 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) ¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ⁶. 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 ¹⁷.
• 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.

The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage” ¹⁸. Pain is a signal in your nervous system that something may be wrong. When there is damage to any part of your body, nerves in that part of the body send messages to your brain. When your brain receives these messages, you feel pain. From a biological perspective, pain is activation of the sensory nervous system’s nociceptive and hypothalamic-pituitary-adrenal axis ¹⁹ and has been described as an aversive sensory and emotional experience typically caused by, or resembling that caused by, actual or potential tissue injury. Nociception refers to the central nervous system (brain and spinal cord) and peripheral nervous system (the nervous system outside the brain and spinal cord) processing of noxious stimuli, such as tissue injury and temperature extremes, which activate pain receptors (nociceptors) and their pathways. Your brain is the central hub for processing signals that come from your body and that typically underpin pain. Your brain not only receives input from damaged tissues but also considers a wide range of psychological and emotional factors. When your brain perceives a threat to your body, your pain experience can be amplified. For example, stress, anxiety, and depression can exacerbate your pain. If someone thinks their pain is a sign of severe damage or will last indefinitely, the sensitivity of the pain system can be increased. On the other hand, understanding that pain doesn’t always correlate with tissue damage and that numerous factors can contribute to pain can lead to less fear and reduced pain perception. Furthermore, relaxation techniques, mindfulness, and positive emotions can help reduce your pain perception.

Pain research has led to some discoveries that might be surprising ¹¹:

• 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 syndrome include fibromyalgia, migraine, headaches, 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 (IBS), inflammatory bowel disease (IBD), interstitial cystitis (painful bladder syndrome), temporomandibular joint dysfunction, and vulvodynia (chronic vulvar pain). It is not known whether these disorders share a common cause. Distress, demoralization and functional impairment often accompany chronic pain syndrome, making it a major source of suffering and economic burden ²⁰.

Chronic pain represents a major healthcare problem worldwide, affecting an estimated 20% of people worldwide, 19% of European adults, 20.4% of US adults and 15% to 20% of visits to doctors ²¹, ²², ²³, ⁵, ²⁴, ²⁵, ²⁶, ²⁷.

Chronic pain is a very common problem. Results from the 2016 National Health Interview Survey show that ²⁸:

• About 50 million U.S. adults (20.4 percent) had chronic pain.
• Nearly 19.6 million adults (8 percent) had high-impact chronic pain.
• In United States the costs for chronic pain are much larger than the annual costs of heart disease, cancer, and diabetes combined ²⁹
• Chronic pain syndrome is reported more commonly in women.
• Chronic pain affects 20% of people worldwide ²².
• Individuals with severe pain had worse health, used more health care, and had more disability than those with less severe pain.
• Chronic pain becomes more common as people grow older, at least in part because health problems that can cause pain, such as osteoarthritis, become more common with advancing age. Military veterans are another group at increased risk for chronic pain; U.S. national survey data show that both pain in general and severe pain are more common among veterans than nonveterans.

Not all people with chronic pain syndrome have a health problem diagnosed by a health care provider, but among those who do, the most frequent conditions by far are low-back pain or osteoarthritis, according to a national survey. Other common diagnoses include rheumatoid arthritis, migraine, carpal tunnel syndrome, and fibromyalgia. The annual economic cost of chronic pain in the United States, including both treatment and lost productivity, has been estimated at up to $635 billion.

Chronic pain may result from an underlying disease or health condition, an injury, medical treatment (such as surgery), inflammation, or a problem in the nervous system (in which case it is called “neuropathic pain”); or the cause may be unknown. Pain can affect quality of life and productivity, and it may be accompanied by difficulty in moving around, disturbed sleep, anxiety, depression, and other problems ³⁰.

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.

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. Sometimes people who have chronic pain may end up having a lot of different examinations and tests to find out what’s causing it, but the tests might not lead to any useful answers. Instead, the tests often find supposed causes of the pain that actually have nothing to do with it. For instance, examinations in people with chronic low back pain may find normal age-related changes in the spine, sometimes leading to the false belief that these changes are causing the pain. Such misleading findings can cause unnecessary anxiety and treatments that don’t work – including unnecessary surgery.

Chronic pain syndrome is a constellation of syndromes that usually do not respond to the medical model of care. Chronic pain syndrome is not always curable, but treatments can help. Chronic pain is managed best with a multidisciplinary approach, requiring good integration and knowledge of multiple organ systems. Medications, acupuncture, local electrical stimulation, and brain stimulation, as well as surgery, are some treatments for chronic pain syndrome. Some physicians use placebos, which in some cases has resulted in a lessening or elimination of pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain syndrome.

Chronic pain classification (ICD 11)

Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized ², ⁷.

Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment.

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

Chronic primary pain

Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. Chronic primary pain is characterized by disability or emotional distress and not better accounted for by another diagnosis of chronic pain. Here, you will find chronic widespread pain, chronic musculoskeletal pain previously termed “non-specific” as well as the primary headaches and conditions such as chronic pelvic pain and irritable bowel syndrome. This is a new phenomenological definition, created because the cause is unknown for many forms of chronic pain. Common conditions such as, for example, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the International Classification of Diseases (ICD) of the World Health Organization (WHO) ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective.

Chronic secondary pain

Chronic secondary pain syndromes are linked to other diseases as the underlying cause, for which pain may initially be regarded as a symptom. The proposed new International Classification of Diseases 11 (ICD-11) codes become relevant as a codiagnosis, when this symptom requires specific care for the patient. This marks the stage when the chronic pain becomes a problem in its own right. In many cases, the chronic pain may continue beyond successful treatment of the initial cause; in such cases, the pain diagnosis will remain, even after the diagnosis of the underlying disease is no longer relevant. It is expected that this new coding will facilitate treatment pathways for patients with these painful conditions by recognizing the chronic pain problem early in the course of the disease. This is also important if the underlying disease is painful in only some of the patients; disease diagnosis alone does not identify these patients without the codiagnosis of chronic pain.

Chronic secondary pain is organized into the following six categories:

Chronic cancer pain

Chronic cancer pain includes pain caused by the cancer itself (the primary tumor or metastases) and pain that is caused by the cancer treatment (surgical, chemotherapy, radiotherapy, and others) ³⁴, ³⁵. Cancer-related pain will be subdivided based on location into visceral, bony (or musculoskeletal), and somatosensory (neuropathic). It will be described as either continuous (background pain) or intermittent (episodic pain) if associated with physical movement or clinical procedures ³⁶.

Pain is a frequent and debilitating accompaniment of cancer and its treatment ³⁷. It becomes more and more apparent that chronic pain syndromes are prevalent in long-term survivors of cancer, and that these chronic secondary pain syndromes include neuropathic and musculoskeletal pains ³⁸. Chronic pain caused by the cancer or by chemotherapy or radiation therapy is coded in this section. Pain that is caused by surgical cancer treatment is coded in the section of chronic postsurgical pain.

Chronic postsurgical and posttraumatic pain

Because pain that persists beyond normal healing is frequent after surgery and some types of injuries, the entity of postsurgical and posttraumatic pain was created. This is defined as pain that develops after a surgical procedure or a tissue injury (involving any trauma, including burns) and persists at least 3 months after surgery or tissue trauma ³⁹; this is a definition of exclusion, as all other causes of pain (infection, recurring malignancy) as well as pain from a pre-existing pain problem need to be excluded. In view of the different causality, as well as from a medicolegal point of view, a separation between postsurgical pain and pain after all other trauma is regarded as useful. Depending on the type of surgery, chronic postsurgical pain is often neuropathic pain (on average 30% of cases with a range from 6% to 54% and more) ⁴⁰. Pain including such a neuropathic component is usually more severe than nociceptive pain and often affects the quality of life more adversely ⁴¹.

Chronic neuropathic pain

Chronic neuropathic pain is caused by a lesion or disease of the somatosensory nervous system ⁴². The somatosensory nervous system provides information about the body including skin, musculoskeletal, and visceral organs. Neuropathic pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyperalgesia) or a painful response to a normally nonpainful stimulus (allodynia). The diagnosis of neuropathic pain requires a history of nervous system injury, for example, by a stroke, nerve trauma, or diabetic neuropathy, and a neuroanatomically plausible distribution of the pain ⁴². For the identification of definite neuropathic pain, it is necessary to demonstrate the lesion or disease involving the nervous system, for example, by imaging, biopsy, neurophysiological, or laboratory tests. In addition, negative or positive sensory signs compatible with the innervation territory of the lesioned nervous structure must be present ⁴³. Diagnostic entities within this category will be divided into conditions of peripheral or central neuropathic pain.

Chronic headache and orofacial pain

The International Headache Society has created a headache classification ⁴⁴ that is implemented in full in the chapter on neurology. This classification differentiates between primary (idiopathic), secondary (symptomatic) headache, and orofacial pain including cranial neuralgias. In the section on chronic pain, only chronic headache and chronic orofacial pain will be included. Chronic headache and chronic orofacial pain is defined as headaches or orofacial pains that occur on at least 50% of the days during at least 3 months. For most purposes, patients receive a diagnosis according to the headache phenotypes or orofacial pains that they currently present. The section will list the most frequent chronic headache conditions.

The most common chronic orofacial pains are temporomandibular disorders ⁴⁵, which have been included in this subchapter of chronic pain. Chronic orofacial pain can be a localized presentation of a primary headache.2 This is common in the trigeminal autonomic cephalalgias, less common in migraines, and rare in tension-type headache. Several chronic orofacial pains such as post-traumatic trigeminal neuropathic pain,3 persistent idiopathic orofacial pain, and burning mouth syndrome are cross-referenced to, eg, primary chronic pain and neuropathic pain. The temporal definition of “chronic” has been extrapolated from that of chronic headaches ⁴⁶.

Chronic visceral pain

Chronic visceral pain is persistent or recurrent pain that originates from the internal organs of the head and neck region and the thoracic, abdominal, and pelvic cavities ⁴⁷. The pain is usually perceived in the somatic tissues of the body wall (skin, subcutis, muscle) in areas that receive the same sensory innervation as the internal organ at the origin of the symptom (referred visceral pain) ⁴⁸. In these areas, secondary hyperalgesia (increased sensitivity to painful stimuli in areas other than the primary site of the nociceptive input) often occurs30; the intensity of the symptom may bear no relationship with the extent of the internal damage or noxious visceral stimulation ⁴⁹. The section on visceral pain will be subdivided according to the major underlying mechanisms, ie, persistent inflammation, vascular mechanisms (ischemia, thrombosis), obstruction and distension, traction and compression, combined mechanisms (eg, obstruction and inflammation concurrently), and referral from other locations. Pain due to cancer will be cross-referenced to the chapter chronic cancer pain and pain due to functional or unexplained mechanisms to chronic primary pain.

Chronic musculoskeletal pain

Chronic musculoskeletal pain is defined as persistent or recurrent pain that arises as part of a disease process directly affecting bone(s), joint(s), muscle(s), or related soft tissue(s). This category is limited to nociceptive pain and does not include pain that may be perceived in musculoskeletal tissues but does not arise therefrom, such as the pain of compression neuropathy or somatic referred pain. The entities subsumed in this approach include those characterized by persistent inflammation of infectious, autoimmune or metabolic etiology, such as rheumatoid arthritis, and by structural changes affecting bones, joints, tendons, or muscles, such as symptomatic osteoarthrosis. Musculoskeletal pain of neuropathic origin will be cross-referenced to neuropathic pain. Well-described apparent musculoskeletal conditions for which the causes are incompletely understood, such as nonspecific back pain or chronic widespread pain, will be included in the section on chronic primary pain.

What are the different types of pain?

Pain researchers differentiate between several types of pain. Pain can be described or categorized depending on how long it lasts or what parts of the body are affected.

Acute pain

Acute pain is pain that starts suddenly and lasts a short time, possibly for a few days or weeks ⁶. It may be mild or severe. Acute pain usually occurs because the body is hurt or injured in some way, but it generally disappears when the body has healed. The treatment of acute pain focuses on blocking pain signal pathways while the tissue heals.

Chronic pain

Chronic pain is pain that lasts longer than three months ⁶. Chronic pain may be due to an ongoing problem but can also develop after any tissue or nerve damage has healed. It is also called persistent pain. For example, you may have ongoing tissue damage and therefore experience chronic pain.

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) ⁶. 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 ¹⁷.

Nociceptive pain

Nociceptive pain is caused by injuries, heat or problems affecting the tissue or organs ¹¹. Examples include pain following bone fractures, colic due to kidney stones, or pain caused by a heart attack. They have an important protective function. In nociceptive pain, the pain messages are sent by special pain receptors known as nociceptors. Depending on what is causing it, the pain might be described as burning, stinging or pounding, for instance. Pain that comes from internal organs is often described as dull, deep or cramp-like, and it’s often hard to say exactly where it hurts.

Breakthrough pain

Breakthrough pain is a sudden flare-up of pain that can occur despite taking regular pain medicine (analgesic) in the setting of relatively well-controlled acute or chronic pain ⁵⁰, ⁵¹, ⁵². Breakthrough pain may happen because the dose of medicine is not high enough or because the pain changes when you move around also called incident pain. Other causes include stress, anxiety or other illnesses. In one study, 75% of patients experienced breakthrough pain; 30% of this pain was incidental, 26% was nonincidental, 16% was caused by end-of-dose failure, and the rest had mixed causes ⁵³.

Incident pain

Incident pain is a type of breakthrough pain related to certain often-defined activities or factors such as movement increasing vertebral body pain from metastatic disease. It is often difficult to treat incident pain effectively because of its episodic nature ⁵⁴.

Nerve pain (neuropathic pain)

Nerve (neuropathic) pain is pain caused by pressure on nerves or the spinal cord, or by nerve damage. The nerve damage or pressure can be in the peripheral nervous system (the nervous system outside the brain and spinal cord) or the central nervous system (spinal cord or brain). People often describe nerve pain as numbness, burning or tingling, or ‘pins and needles’. Nerve pain can occur anywhere nerves get damaged, and the pain may come and go.

Causes of neuropathic (nerve) pain of particular relevance to cancer include chemotherapy (e.g., vinca alkaloids), infiltration of the nerve roots by tumor, or damage to nerve roots (radiculopathy) or groups of nerve roots (plexopathy) due to tumor masses or treatment complications (e.g., radiation plexopathy) ⁵⁵. Nerve (neuropathic) pain may be evoked by stimuli or spontaneous. Patients who experience pain from nonnoxious stimuli are classified as having allodynia. Allodynia is a condition where a stimulus that normally wouldn’t cause pain results in pain. For example, a light touch from a feather might feel painful instead of just a sensation. Other examples include pain from wearing clothing, temperature changes, or someone gently tapping your shoulder. Hyperalgesia is an abnormally increased sensitivity to feeling pain and an extreme response to pain, which may be caused by damage to pain receptors (nociceptors) or peripheral nerves and can cause hypersensitivity to stimulus. Pain receptors are found in somatic (e.g., muscles, skin, joints, connective tissue, or bones) and visceral tissues (internal organs).

Pain caused by an inflammation

Pain caused by an inflammation is caused when the immune system launches an inflammatory response – for instance, to an infection. Like pain caused by tissue damage, it has a protective function. In some diseases, though, the immune system attacks the body’s own cells and leads to long-lasting inflammations that can cause chronic pain. One example of this kind of disease is rheumatoid arthritis.

Bone pain

Bone pain is pain caused by cancer spreading to the bones and damaging bone tissue in one or more areas. It is often described as dull, aching or throbbing, and it may be worse at night.

Soft tissue pain

Soft tissue pain is pain caused by damage to or pressure on soft tissue, including muscle. The pain is often described as sharp, aching or throbbing.

Visceral pain

Visceral pain is pain caused by damage to or pressure on internal organs. Visceral pain can be difficult to pinpoint. It may cause some people to feel sick in the stomach and is often described as having a throbbing sensation.

A specific type of visceral pain is referred pain, which is explained by the commingling of nerve fibers from somatic (e.g., muscles, skin, joints, connective tissue, or bones) and visceral pain receptors (nociceptors) at the level of the spinal cord. Patients mistakenly interpret the pain as originating from the innervated somatic tissue (e.g., muscles, skin, joints, connective tissue, or bones). Visceral pain may be accompanied by autonomic signs such as sweating, pallor, or bradycardia. Somatic pain is more easily localized.

Referred pain

Referred pain is pain that is felt in a different area of the body from the area that is damaged.

Localized pain

Localized pain is pain at the spot where there’s a problem.

Phantom pain

Phantom pain is a pain sensation in a body part that is no longer there, such as breast pain after the breast has been removed. This type of pain is very real.

Dysfunctional pain

Sometimes pain is caused by a problem with the processing of pain in the brain. Dysfunctional pain is often non-specific – in other words, there is no known cause and it can be triggered by many things. Because there is no “reason” for the pain and it has no physiological purpose, it is also referred to as “dysfunctional pain”. Examples of this kind of pain syndrome include fibromyalgia, irritable bowel syndrome (IBS) and a type of chronic bladder inflammation (interstitial cystitis).

Chronic pain vs Fibromyalgia

Chronic pain is an umbrella term referring to pain that lasts 3 to 6 months or pain that persists past “normal healing time” ¹, ², ³, ⁴, ⁵.

Footnote: The dots indicate the 18 tenderness points important for the diagnosis of fibromyalgia.

Fibromyalgia causes

The exact cause of fibromyalgia is unknown, but fibromyalgia is thought to be related to abnormal levels of certain chemicals in the brain and changes in the way the central nervous system (brain, spinal cord and nerves) processes pain messages carried around the body ⁷², ⁷³, ⁷⁴. Current evidence describes fibromyalgia pain as the result of a complex evaluative process of environmental and multisystem information ⁷⁵, ⁷⁶. For this reason, currently, pain is considered a personal somatic experience in response to a threat to bodily or existential integrity ⁷⁷. Pain and sensory processing alterations in the central nervous system (brain and spinal cord) are present in fibromyalgia ⁷⁴. Patients perceive noxious stimuli as being painful at lower levels of physical stimulation compared to healthy controls ⁷⁸. With rapidly repetitive short noxious stimuli to fibromyalgia patients, they experience higher than normal increases in the perceived intensity of pain. There appears to be a deficiency in the endogenous analgesic systems in patients with fibromyalgia. There has been a demonstration of differences in activation of areas of the brain which are pain-sensitive areas by functional neuroimaging techniques ⁷⁹.

There is no evidence of any single event cause of fibromyalgia; instead, it is triggered or aggravated by multiple physical and/or emotional stressors which include infections as well as emotional and physical trauma ⁷⁹.

It’s also suggested that some people are more likely to develop fibromyalgia because of genes inherited from their parents, though there is no documentation of a definitive candidate gene ⁸⁰.

There is most often some triggering factor that sets off fibromyalgia. It may be spine problems, arthritis, injury, or other type of physical stress. Emotional stress also may trigger fibromyalgia. The result is a change in the way your body “talks” with your spinal cord and brain. Levels of brain chemicals and proteins may change. More recently, fibromyalgia has been described as Central Pain Amplification disorder, meaning the volume of pain sensation in the brain is turned up too high.

In many cases, fibromyalgia appears to be triggered by a physically or emotionally stressful event, such as:

• an injury or infection
• giving birth
• having an operation
• the breakdown of a relationship
• the death of a loved one
• illness or other diseases
• post-traumatic stress disorder (PTSD)
• repetitive injuries
• obesity.

Here are some of the main factors thought to contribute to fibromyalgia:

Abnormal pain messages

One of the main theories is that people with fibromyalgia have developed changes in the way the central nervous system processes the pain messages carried around the body. This could be due to changes to chemicals in the nervous system.

The central nervous system (brain, spinal cord and nerves) transmits information all over your body through a network of specialized cells. Changes in the way this system works may explain why fibromyalgia results in constant feelings of, and extreme sensitivity to, pain.

Chemical imbalances

Research has found that people with fibromyalgia have abnormally low levels of the hormones serotonin, noradrenaline and dopamine in their brains.

Low levels of these hormones may be a key factor in the cause of fibromyalgia, as they’re important in regulating things such as:

• mood
• appetite
• sleep
• behavior
• your response to stressful situations

These hormones also play a role in processing pain messages sent by the nerves. Increasing the hormone levels with medication can disrupt these signals.

Some researchers have also suggested that changes in the levels of some other hormones, such as cortisol (which is released when the body is under stress), may contribute to fibromyalgia.

Sleep problems

It’s possible that disturbed sleep patterns may be a cause of fibromyalgia, rather than just a symptom.

Fibromyalgia can prevent you from sleeping deeply and cause fatigue (extreme tiredness). People with the condition who sleep badly can also have higher levels of pain, suggesting that these sleep problems contribute to the other symptoms of fibromyalgia.

Genetics

Research has suggested that genetics may play a small part in the development of fibromyalgia, with some people perhaps more likely than others to develop the condition because of their genes, although there is no evidence of a definitive gene has been found ⁸⁰. Currently, about 100 genes that regulate pain are believed to be relevant to pain sensitivity or analgesia. The main genes are those encoding for voltage-dependent sodium channels, GABAergic pathway proteins, mu-opioid receptors, catechol-O-methyltransferase and GTP cyclohydrolase 1 ⁸¹. Further studies are needed to understand the role of these genes in chronic pain conditions such as fibromyalgia.

Associated conditions

There are several other conditions often associated with fibromyalgia. Generally, these are rheumatic conditions (affecting the joints, muscles and bones), such as:

• Osteoarthritis – when damage to the joints causes pain and stiffness
• Lupus – when the immune system mistakenly attacks healthy cells and tissues in various parts of the body
• Rheumatoid arthritis – when the immune system mistakenly attacks healthy cells in the joints, causing pain and swelling
• Ankylosing spondylitis – pain and swelling in parts of the spine
• Temporomandibular disorder – a condition that can cause pain in the jaw, cheeks, ears and temples

Conditions such as these are usually tested for when diagnosing fibromyalgia.

Possible triggers

Fibromyalgia is often triggered by a stressful event, including physical stress or emotional (psychological) stress. Possible triggers for the condition include:

• an injury
• a viral infection
• giving birth
• having an operation
• the breakdown of a relationship
• being in an abusive relationship
• the death of a loved one

However, in some cases, fibromyalgia doesn’t develop after any obvious trigger.

Risk factors for fibromyalgia

Known risk factors for fibromyalgia include:

• Age. Fibromyalgia can affect people of all ages, including children. However, most people are diagnosed during middle age and you are more likely to have fibromyalgia as you get older.
• Lupus or Rheumatoid Arthritis. If you have lupus or rheumatoid arthritis (RA), you are more likely to develop fibromyalgia.

Some other factors have been weakly associated with onset of fibromyalgia, but more research is needed to see if they are real. These possible risk factors include:

• Sex. Women are seven times as likely to have fibromyalgia as men.
• Stressful or traumatic events, such as car accidents, post-traumatic stress disorder (PTSD).
• Repetitive injuries. Injury from repetitive stress on a joint, such as frequent knee bending.
• Illness (such as viral infections).
• Family history. You may be more likely to develop fibromyalgia if a parent or sibling also has fibromyalgia.
  
• Obesity.

Fibromyalgia symptoms

Fibromyalgia has many symptoms that tend to vary from person to person. The main symptom is widespread pain. The pain associated with fibromyalgia often is described as a constant dull ache that has lasted for at least three months. To be considered ‘widespread pain’, the pain must occur on both sides of your body and above and below your waist.

Symptoms of fibromyalgia include:

• Widespread pain. The pain associated with fibromyalgia often is described as a constant dull ache that has lasted for at least three months. To be considered widespread, the pain must occur on both sides of your body and above and below your waist.
• Fatigue. People with fibromyalgia often awaken tired, even though they report sleeping for long periods of time. Sleep is often disrupted by pain, and many patients with fibromyalgia have other sleep disorders, such as restless legs syndrome and sleep apnea.
• Cognitive difficulties. A symptom commonly referred to as “fibro fog” impairs the ability to focus, pay attention and concentrate on mental tasks.

People with fibromyalgia may also have other symptoms, such as:

• Trouble sleeping
• Morning stiffness
• Headaches
• Painful menstrual periods
• Tingling or numbness in hands and feet
• Problems with thinking and memory (sometimes called “fibro fog”)

There may be periods when your symptoms get better or worse, depending on factors such as:

• your stress levels
• changes in the weather
• how physically active you are

Fibromyalgia often co-exists with other painful conditions, such as:

• Anxiety
• Depression
• Irritable bowel syndrome (IBS)
• Restless legs syndrome
• Migraine and other types of headaches
• Interstitial cystitis or painful bladder syndrome
• Temporomandibular joint disorders
• Increased sensitivity to odors, bright lights, loud noises, or medicines.
• Dry eyes or mouth.
• Dizziness and problems with balance.
• Problems with memory or concentration (sometimes called the “fibro fog”).
• For women, painful menstrual periods.

Fibromyalgia complications

Fibromyalgia can cause pain, disability, and lower quality of life. US adults with fibromyalgia may have complications such as:

• More hospitalizations. If you have fibromyalgia you are twice as likely to be hospitalized as someone without fibromyalgia.
• Lower quality of life. Women with fibromyalgia may experience a lower quality of life.
• Higher rates of major depression. Adults with fibromyalgia are more than 3 times more likely to have major depression than adults without fibromyalgia. Screening and treatment for depression is extremely important.
• Higher death rates from suicide and injuries. Death rates from suicide and injuries are higher among fibromyalgia patients, but overall mortality among adults with fibromyalgia is similar to the general population.
• Higher rates of other rheumatic conditions. Fibromyalgia often co-occurs with other types of arthritis such as osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis.

Fibromyalgia diagnosis

If you think you have fibromyalgia, visit your doctor. Diagnosing fibromyalgia can be difficult, as there’s no specific test to diagnose the condition ⁸². And the symptoms of fibromyalgia, such as pain, sleep problems and fatigue, are common in many other conditions and can vary. It sometimes takes visits to several different health care providers to get a diagnosis.

During diagnosis, you’ll be asked about how your symptoms are affecting your daily life. If you have had any trouble sleeping or fatigue, tell your doctor how long you have had this problem. Your doctor may ask whether you have been feeling anxious or depressed since your symptoms began.

Your body will also be examined to check for visible signs of other conditions – for example, swollen joints may suggest arthritis, rather than fibromyalgia.

In the past, doctors would check 18 specific points on a person’s body to see how many of them were painful when pressed firmly (see Figure 1). Newer 2016 guidelines from the American College of Rheumatology don’t require a tender point exam. Instead, the main factor needed for a fibromyalgia diagnosis is widespread pain throughout your body for at least three months ⁸³.

Fibromyalgia may now be diagnosed in adults when all of the following criteria are met ⁸³:

1. Generalized pain, defined as pain in at least 4 of 5 regions, is present.
2. Symptoms have been present at a similar level for at least 3 months.
3. Widespread pain index (WPI) ≥ 7 and symptom severity scale (SSS) score ≥ 5 OR WPI of 4–6 and SSS score ≥ 9.
4. A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses.

To meet the American College of Rheumatology 2016 criteria, you must have pain in at least four of these five areas:

• Left upper region, including shoulder, arm or jaw
• Right upper region, including shoulder, arm or jaw
• Left lower region, including hip, buttock or leg
• Right lower region, including hip, buttock or leg
• Axial region, which includes neck, back, chest or abdomen.

Old guidelines required tender points

Fibromyalgia is also often characterized by additional pain when firm pressure is applied to specific areas of your body, called tender points. In the past, at least 11 of these 18 spots had to test positive for tenderness to diagnose fibromyalgia.

But fibromyalgia symptoms can come and go, so a person might have 11 tender spots one day but only eight tender spots on another day. And many family doctors were uncertain about how much pressure to apply during a tender point exam. While specialists or researchers may still use tender points, an alternative set of guidelines has been developed for doctors to use in general practice.

These newer diagnostic criteria include:

• Widespread pain lasting at least three months
• Presence of other symptoms such as fatigue, waking up tired and trouble thinking
• No other underlying condition that might be causing the symptoms.

Criteria for diagnosing fibromyalgia

1990 American College of Rheumatology classification criteria was used in many clinical and therapeutic trials but has not been useful in diagnosing fibromyalgia in clinical practice.

The 1990 American College of Rheumatology fibromyalgia classification criteria included:

• Symptoms of widespread pain, present on both sides of the body and both above and below the waist
• Physical findings of at minimum 11 of 18 defined tender points:
  1. Suboccipital muscle insertion bilaterally
  2. Anterior aspect of C5 to C7 intertransverse spaces bilaterally
  3. Mid upper border of trapezius bilaterally
  4. Origin of supraspinatus muscle bilaterally
  5. Second costochondral junctions bilaterally
  6. 2cm distal to the lateral epicondyles bilaterally
  7. Upper outer quadrants of buttocks bilaterally
  8. Greater trochanteric prominence bilaterally
  9. Medial fat pad of the knees bilaterally

The pressure appropriate for detecting these tender points should be equal to 4 kg/cm², enough to whiten the nail bed of the fingertip of the examiner.

For the purposes of classification, the patient is said to have fibromyalgia if both criteria are met.

There were a number of limitations of the 1990 1990 American College of Rheumatology diagnostic criteria, which include the following:

• Physicians do not know how to examine tender points, perform the exam incorrectly, or refuse to do so.
• A number of symptoms that were previously not considered were increasingly appreciated as key symptoms of fibromyalgia.
• The criteria set the bar so high that it left little room for variation among fibromyalgia patients. Also, the patient whose symptoms improved failed to satisfy the 1990 criteria.

Criteria Needed for a Fibromyalgia Diagnosis (American College of Rheumatology Fibromyalgia Diagnostic Criteria 2010) ⁸⁴

1. Pain and symptoms over the past week, based on the total of number of painful areas out of 19 parts of the body plus level of severity of these symptoms:
   • a. Fatigue
   • b. Waking unrefreshed
   • c. Cognitive (memory or thought) problems
   • Plus number of other general physical symptoms
2. Symptoms lasting at least three months at a similar level
3. No other health problem that would explain the pain and other symptoms

Revised 2016 American College of Rheumatology guidelines don’t require a tender point exam. Instead, the main factor needed for a fibromyalgia diagnosis is widespread pain throughout your body for at least three months ⁸³.

Fibromyalgia may now be diagnosed in adults when all of the following criteria are met ⁸³:

1. Generalized pain, defined as pain in at least 4 of 5 regions, is present.
2. Symptoms have been present at a similar level for at least 3 months.
3. Widespread pain index (WPI) ≥ 7 and symptom severity scale (SSS) score ≥ 5 OR WPI of 4–6 and SSS score ≥ 9.
4. A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses.

Note:

• Widespread pain index (WPI): note the number of areas where and how many areas the patient has had pain in the prior week. The score will be between 0 and 19. Shoulder girdle, left hip (buttock, trochanter), left jaw, left upper back shoulder girdle, right hip (buttock, trochanter), right jaw, right lower back upper arm, left upper leg, left chest neck upper arm, right upper leg, right abdomen lower arm, left lower leg, left lower arm, right lower leg, right
• Symptom severity scale (SSS): Fatigue, waking unrefreshed, and cognitive symptoms. For each of the three symptoms above, indicate the severity level over the past week utilizing the following scale: 0 no problem; 1 slight or mild problems, generally mild or intermittent; 2 moderate, considerable problems, often present and/or at a moderate level; 3 severe: pervasive, continuous, life-disturbing problems. Considering somatic symptoms in general, indicate whether the patient has: 0 for no symptoms, 1 for a few symptoms, 2 for a moderate number of symptoms, and 3 for many symptoms. The symptom severity scale (SSS) sums the severity of the 3 symptoms (fatigue, waking unrefreshed, cognitive symptoms) plus the severity) of general somatic symptoms. The final score is between 0 and 12.

To meet the American College of Rheumatology 2016 criteria, you must have pain in at least four of these five areas:

• Left upper region, including shoulder, arm or jaw
• Right upper region, including shoulder, arm or jaw
• Left lower region, including hip, buttock or leg
• Right lower region, including hip, buttock or leg
• Axial region, which includes neck, back, chest or abdomen

Figure 2. Fibromyalgia diagnostic criteria

Ruling out other conditions

If your doctor thinks you may have fibromyalgia, they’ll first have to rule out all other conditions that could be causing your symptoms. These conditions may include:

• Chronic fatigue syndrome (also known as myalgic encephalomyelitis) – a condition that causes long-term tiredness
• Rheumatic diseases. Certain conditions — such as rheumatoid arthritis, Sjogren’s syndrome and lupus — can begin with generalized aches and pain.
• Mental health problems. Disorders such as depression and anxiety often feature generalized aches and pain.
• Neurological disorders. In some people, fibromyalgia causes numbness and tingling, symptoms that mimic those of disorders such as multiple sclerosis and myasthenia gravis.

Tests to check for some of these conditions include urine and blood tests, although you may also have X-rays and other scans.

Blood tests may include:

• Complete blood count
• Erythrocyte sedimentation rate
• Cyclic citrullinated peptide test
• Rheumatoid factor
• Thyroid function tests
• Anti-nuclear antibody
• Celiac serology
• Vitamin D

If there’s a chance that you may be suffering from sleep apnea, your doctor may recommend an overnight sleep study.

If you’re found to have another condition, you could still have fibromyalgia as well.

Fibromyalgia test

Fibromyalgia is usually diagnosed by documenting the patient’s medical history, ruling out disorders and diseases that may be mimicking or exacerbating fibromyalgia, and by utilizing the criteria last updated by the American College of Rheumatology in 2016 ⁶³, ⁶⁴, ⁸³, ⁸⁵.

Revised American College of Rheumatology 2016 guidelines don’t require a tender point exam. Instead, the main factor needed for a fibromyalgia diagnosis is widespread pain throughout your body for at least three months ⁸³.

Fibromyalgia may now be diagnosed in adults when all of the following criteria are met ⁸³:

1. Generalized pain, defined as pain in at least 4 of 5 regions, is present.
2. Symptoms have been present at a similar level for at least 3 months.
3. Widespread pain index (WPI) ≥ 7 and symptom severity scale (SSS) score ≥ 5 OR WPI of 4–6 and SSS score ≥ 9.
4. A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses.

To meet the American College of Rheumatology 2016 criteria, you must have pain in at least four of these five areas ⁸³:

• Left upper region, including shoulder, arm or jaw
• Right upper region, including shoulder, arm or jaw
• Left lower region, including hip, buttock or leg
• Right lower region, including hip, buttock or leg
• Axial region, which includes neck, back, chest or abdomen.

Laboratory Tests

Laboratory tests can be useful to help diagnose conditions with symptoms similar to fibromyalgia, such as rheumatoid arthritis, Sjögren syndrome, thyroid disease, and lupus. It is not usually cost effective or necessary to do extensive screening. General tests that may be ordered include:

• Comprehensive metabolic panel – to examine electrolytes, proteins, liver and kidney function, calcium, and glucose
• CBC (complete blood count) – to look for anemia, a possible cause of weakness and fatigue
• TSH (thyroid stimulating hormone) and/or other thyroid testing since hypothyroidism can cause symptoms similar to fibromyalgia
• ANA (anti-nuclear antibody) – to rule out autoimmune disorders, such as lupus or Sjogren syndrome
• CK (creatine kinase) – to rule out other conditions that can cause muscle weakness or pain
• Erythrocyte sedimentation rate (ESR)
• Cyclic citrullinated peptide test
• Rheumatoid factor
• Celiac serology
• Vitamin D

A healthcare practitioner will typically consider the following in developing a diagnosis: results of the general tests, the patient’s history (including family history and risk factors for certain diseases), and results of the physical examination. Based on these findings, some additional tests could be done.

Meanwhile, researchers continue to look for new testing protocols that may be more specific for fibromyalgia.

Non-Laboratory Tests

Electromyography (EMG) may be performed to assess the health of muscles and the nerves that control them. Occasionally, an imaging scan such as an MRI (magnetic resonance imaging) may be ordered to help rule out the possibility of multiple sclerosis or other diseases that may cause symptoms similar to fibromyalgia.

More clues for fibromyalgia diagnosis

People who have fibromyalgia also often wake up tired, even after they’ve slept continuously for more than eight hours. Brief periods of physical or mental exertion may leave them exhausted. They may also have problems with short-term memory and the ability to concentrate. If you have these problems, your doctor may ask you to rank how severely they affect your day-to-day activities.

Fibromyalgia often coexists with other health problems, so your doctor may also ask if you experience:

• Irritable bowel syndrome (IBS)
• Headaches
• Jaw pain
• Anxiety or depression
• Frequent or painful urination

Possible fibromyalgia triggers

In some cases, fibromyalgia symptoms begin shortly after a person has experienced a mentally or physically traumatic event, such as a car wreck. People who have post-traumatic stress disorder appear to be more likely to develop fibromyalgia, so your doctor may ask if you’ve experienced any traumatic events recently.

Because a genetic factor appears to be involved in fibromyalgia, your doctor may also want to know if any other members of your immediate family have experienced similar symptoms.

All this information taken together will give your doctor a much better idea of what may be causing your symptoms. And that determination is crucial to developing an effective treatment plan.

2010 American College of Rheumatology Preliminary Diagnostic Criteria

To address the aforementioned issues the American College of Rheumatology in 2010 proposed the preliminary diagnostic criteria for fibromyalgia (Table 2), that were not meant to replace the 1990 American College of Rheumatology classification criteria, but to represent an alternative simple and easy method of diagnosis in clinical practice (40). These diagnostic criteria do not require a tender point count. Instead they rely only on symptoms for the diagnosis of fibromyalgia. They introduced the widespread pain index (WPI), which counts the areas that the patient feels pain during one week preceding the examination, and the symptom severity (SS) scale, which describes the severity of fatigue, unrefreshing sleep, cognitive problems, and a number of associated somatic fibromyalgia symptoms. These symptoms need to be assessed and rated by a physician. The 2010 American College of Rheumatology preliminary diagnostic criteria are in-adequate for patient self-diagnosis.

Two more conditions need to be fulfilled. The symptoms need to be present at a similar level for at least 3 months while alternate disorders that would otherwise explain the pain need to be excluded (Table 2). The authors of the 2010 American College of Rheumatology preliminary diagnostic criteria have clarified that the latter condition does not mean that fibromyalgia is an exclusion diagnosis according to these criteria. The diagnosis of fibromyalgia should not be made only when there is not another disease that could explain the pain that would otherwise be attributed to fibromyalgia. It should be noted that rheumatic diseases usually do not cause pain that can be confused with fibromyalgia ⁸⁶.

There is evidence that there is good agreement between the 1990 American College of Rheumatology classification criteria and the 2010 American College of Rheumatology preliminary diagnostic criteria ⁸⁷. However, these criteria are expected not to agree completely, as the former are focused on the presence of tender points while the latter on the presence of symptoms. The 1990 criteria can diagnose fibromyalgia in patients who do not have sufficiently high symptom score according to the 2010 criteria, while the 2010 criteria can diagnose fibromyalgia in patients who do not have sufficient tender points according to the 1990 criteria.

The introduction of the 2010 American College of Rheumatology preliminary diagnostic criteria was surrounded by controversy too. In particular, they have been criticized for being completely symptom focused, ill-defined, and lucking some mechanistic features of fibromyalgia, such as hyperalgesia, central sensitization and dysfunctional pain modulation ⁸⁸. Additionally, these diagnostic criteria are based on the subjective assessment of the patient’s somatic symptoms by the physician, adding ambiguity and influencing repeatability among different physicians ⁸⁹. A self-reported version of the 2010 American College of Rheumatology preliminary diagnostic criteria was developed, so as to be used in survey research, and not in clinical practice ⁹⁰. These criteria are known as the modified 2010 American College of Rheumatology preliminary diagnostic criteria or the research criteria. They introduced the fibromyalgia severity (FS) score (originally called fibromyalgianess scale) which is the sum of the self-reported widespread pain index (WPI) and symptom severity (SS) score. This score can be used as an approximate measure of the severity of fibromyalgia. The fibromyalgia severity (FS) score has also been called polysymptomatic distress (PSD) scale. It has been proposed that the markers of physical and psychological distress have a continuous distribution in the general population with fibromyalgia patients being at the extreme end of this distribution ⁹¹. The polysymptomatic distress (PSD) scale could be useful to define the position of each individual in this continuum, without having to differentiate between patients with fibromyalgia and those without, as this distinction can sometimes be unclear if not arbitrary ⁹².

Table 2. 2010 American College of Rheumatology Preliminary Diagnostic Criteria

2016 Revisions to the 2010/2011 Fibromyalgia Diagnostic Criteria

A limitation of the widespread pain index (WPI) is the fact that it counts the number of painful areas without considering their distribution in the body. Patients with regional pain disorders can fulfill the 2010 American College of Rheumatology preliminary diagnostic criteria since pain can be located in 3 or more areas in the same region ⁹³. To overcome this issue the 2016 revision of the diagnostic criteria require the pain to be generalized (multisite pain). The areas widespread pain index (WPI) assesses are divided in 5 regions (Table 3) and the diagnosis of fibromyalgia requires the distribution of pain in 4 out of 5 regions ⁹⁴. The jaw, the chest and the abdomen area are problematic when they are used to define a region. In this way they are excluded from the definition of generalized pain ⁹⁵. Since pain needs to be located in at least 4 areas according to the 2016 revision, the previous criterion for diagnosis, widespread pain index (WPI) of 3-6 and symptom severity (SS) scale score ≥9 was changed to widespread pain index (WPI) of 4-6 and symptom severity (SS) scale score ≥9.

The 2010 and 2011 criteria are extremely similar. Their difference is that the 2010 criteria are physician-based and can be used in clinical practice for the diagnosis of fibromyalgia, while the 2011 criteria are self-reported and can be used only in survey research. According to the 2010 criteria the symptom severity (SS) scale assesses a wide range of somatic symptoms, which makes them impractical for use in questionnaires. With the 2016 revision the assessment of somatic symptoms that is included in the symptom severity (SS) scale is limited to headaches, pain and cramps in the lower abdomen and depression. In this way, there is no longer need for different criteria for clinical practice and for survey research. The same criteria can be used in both settings having 2 different methods of administration.

One prerequisite for diagnosis of fibromyalgia according to the 2010 American College of Rheumatology preliminary diagnostic criteria is the patient not to have a condition that would otherwise explain the pain. The authors of these criteria clarified that this does not mean that the diagnosis of fibromyalgia is an exclusion diagnosis. However, this phrasing was not considered clear enough and caused significant misunderstanding. In this way this criterion was removed in the 2016 revision. The diagnosis of fibromyalgia can be valid even if there is another condition that can cause the pain that is attributed to fibromyalgia. According to this definition fibromyalgia can coexist with other clinically significant conditions that can cause pain.

Table 3. 2016 Fibromyalgia Diagnostic Criteria

AAPT Diagnostic Criteria

In an attempt to improve the recognition of fibromyalgia in clinical practice, the ACTTION-APS Pain Taxonomy (AAPT) fibromyalgia working group proposed new diagnostic criteria in 2018 ⁹⁶. These criteria are similar to the American College of Rheumatology criteria as they require the pain to be generalized (multisite), require the presence of non-pain symptoms and require the symptoms to be present for at least 3 months. These diagnostic criteria are more simple than the American College of Rheumatology criteria and they can be easily implemented in primary clinical practice, but some of their aspects have been criticized ⁹⁷. According to the AAPT criteria the head, the abdomen and the chest are included in the areas that are assessed for the presence of generalized musculoskeletal pain. However, these regions are problematic since pain originating from the teeth, the heart and the bowel can be referred to these areas. Additionally, the AAPT criteria do not have the ability to quantify the severity of fibromyalgia as, apart from the generalized pain, they only assess the presence or absence of the 2 most common non-pain symptoms of fibromyalgia, abolishing all other somatic symptoms.

ACTTION-APS Pain Taxonomy (AAPT) Diagnostic Criteria ⁹⁸

• Multisite pain defined as 6 or more pain sites from a total of 9 possible sites:
  • Head
  • Left arm
  • Right arm
  • Chest
  • Abdomen
  • Upper back and spine
  • Lower back and spine, including buttocks
  • Left leg
  • Right leg
• Moderate to severe sleep problems or fatigue
• Multisite pain plus fatigue or sleep problems must have been present for at least 3 months

NOTE. The presence of another pain disorder or related symptoms does not rule out a diagnosis of fibromyalgia. However, a clinical assessment is recommended to evaluate for any condition that could fully account for the patient’s symptoms or contribute to the severity of the symptoms.

Fibromyalgia treatment

Not all health care providers are familiar with fibromyalgia and its treatment. You should see a doctor who specializes in the treatment of fibromyalgia. In some cases, fibromyalgia may require a healthcare team that may include your primary care physician, a rheumatologist, a physical therapist and a mental health professional. The treatment should be individualized based on the symptoms, the comorbidities and the preferences of the patient, who should be encouraged to participate in the decision-making process of selecting the optimal therapies ⁹⁹.

The treatment of fibromyalgia is challenging because of current limited understanding of its pathogenesis and the poor response of patients to conventional pain treatments. The goal of treatment is to tackle different symptoms (pain, fatigue, sleep and emotional problems) at the same time. Treatment options for fibromyalgia help to reduce pain, stress and fatigue, treat depression, improve sleep and help people understand what triggers symptoms and how to manage them.

Your doctor may recommend treating your symptoms with acetaminophen (paracetamol) first. He or she may also recommend an anti-depressant, such as duloxetine or milnacipran. Anti-seizure medicines, such as preglabin, may also be effective in managing your pain. Nonsteroidal anti-inflammatory medicines (which include ibuprofen, aspirin, and naproxen) are not usually effective in treating fibromyalgia when taken alone.

No one treatment works for all symptoms, but trying a variety of treatment strategies can have a cumulative effect.

Making changes in your lifestyle and daily habits can help you feel better. Remember, your treatment won’t be as effective if you don’t take an active role in your health care. The following are some ways you can take an active role in managing your fibromyalgia symptoms.

Patient education

The first step should be the education of the patient. The patients with fibromyalgia need to understand their illness before any treatment modality is used ¹⁰⁰. Providing a diagnosis, “labeling” the patient with fibromyalgia, may have beneficial effects. It has been shown that fewer symptoms and an improvement in health status is noted after the patients are informed of their diagnosis ¹⁰¹. The physician should clarify that fibromyalgia is a real illness and the symptoms the patient experiences are not imaginary. The role of neurotransmitters and neuromodulators in pain perception, fatigue, abnormal sleep and mood disturbances should be discussed, so as the patient to understand the rationale of the pharmacologic therapy, especially when antidepressant drugs are used. The patient also needs to acknowledge that fibromyalgia is a chronic relapsing condition without though being life-threatening nor deforming.

Self-help

If you have fibromyalgia, there are several ways to change your lifestyle to help relieve your symptoms and make your condition easier to live with.

Your doctor, or another healthcare professional treating you, can offer advice and support about making these changes part of your everyday life.

There are organizations to support people with fibromyalgia that may also be able to offer advice.

• Self-Management Resource Center: https://www.selfmanagementresource.com/
• Chronic Disease Self-Management Program in your area here: http://www.eblcprograms.org/evidence-based/map-of-programs/
• UK Fibromyalgia’s support group: http://ukfibromyalgia.com/index.php
• Fibromyalgia Action UK: https://healthunlocked.com/fibromyalgia-action-uk

Exercise

One of the best things you can do if you have fibromyalgia is engage in moderate exercise on a regular basis. Exercise can reduce your pain, give you more energy, reduce stress, and help you sleep better. If you’re not used to exercising, be sure to talk to your doctor before you start. If you have a physical therapist on your health care team, he or she can help you develop an exercise routine that’s right for you. It’s usually best to start with low-impact aerobic exercise (for example, walking or water aerobics) for a short period of time a few days a week. As your pain decreases and your energy increases, you can gradually increase the intensity and frequency of your exercise.

It has been reported that an exercise program incorporating aerobic, strengthening and flexibility elements can lead to greater benefits than a relaxation program. Exercise in fibromyalgia patients should have two major components: strengthening to increase soft-tissue length and joint mobility, and aerobic conditioning to increase fitness and function, reduce fibromyalgia symptoms and improve quality of life ¹⁰². Exercise should be of low impact and of sufficient intensity so as to be able to change aerobic capacity ¹⁰³. Successful interventions include fast walking, biking, swimming, water aerobics, tai chi and yoga. Land and aquatic training appears to be equally beneficial ¹⁰⁴. It has been suggested that in the presence of exercise-induced pain, the intensity and duration of exercise should be reduced, while its frequency should be maintained, so as to avoid any further decrease in exercise tolerance ¹⁰⁵. The type and intensity of the exercise program should be individualized and should be based upon patient preference and the presence of any other cardiovascular, pulmonary, or musculoskeletal comorbidities.

Aerobic exercise

Aerobic activities are any kind of rhythmic, moderate-intensity exercises that increase your heart rate and make you breathe harder. Examples include:

• walking
• cycling
• swimming

Research suggests that aerobic fitness exercises should be included in your personalised exercise plan, even if you can’t complete these at a high level of intensity. For example, if you find jogging too difficult, you could try brisk walking instead.

A review of a number of studies found that aerobic exercises may improve quality of life and relieve pain. As aerobic exercises increase your endurance (how long you can keep going), these may also help you function better on a day-to-day basis.

Resistance and strengthening exercises

Resistance and strengthening exercises are those that focus on strength training, such as lifting weights. These exercises need to be planned as part of a personalised exercise programme; if they aren’t, muscle stiffness and soreness could be made worse.

A review of a number of studies concluded that strengthening exercises may improve:

• muscle strength
• physical disability
• depression
• quality of life

People with fibromyalgia who completed the strengthening exercises in these studies said they felt less tired, could function better and experienced a boost in mood.

Improving the strength of your major muscle groups can make it easier to do aerobic exercises.

Pacing yourself

If you have fibromyalgia, it’s important to pace yourself. This means balancing periods of activity with periods of rest, and not overdoing it or pushing yourself beyond your limits.

If you don’t pace yourself, it could slow down your progress in the long term. Over time, you can gradually increase your periods of activity, while making sure they’re balanced with periods of rest.

If you have fibromyalgia, you will probably have some days when your symptoms are better than others. Try to maintain a steady level of activity without overdoing it, but listen to your body and rest whenever you need to.

Avoid any exercise or activity that pushes you too hard, because this can make your symptoms worse. If you pace your activities at a level that’s right for you, rather than trying to do as much as possible in a short space of time, you should make steady progress.

For example, it may help to start with gentler forms of exercise – such as tai chi, yoga and pilates – before attempting more strenuous aerobic or strengthening exercises.

Cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT) has been proven effective for managing fibromyalgia symptoms. One of the goals of the fibromyalgia treatment should be to help patients understand the effect of thoughts, beliefs and expectations on their symptoms. With the help of a trained mental health counselor, a person learns how to change negative thought patterns and behaviors to relieve pain, promote better sleep and improve functioning. This can help them to abolish the perception of helplessness and the catastrophizing thoughts that can adversely influence their condition. Patients with greater self-efficacy are more likely to have a good response to treatment programs and experience better outcomes. The beneficial effect of cognitive-behavioral therapies in fibromyalgia patients with anxiety and depression disorders is limited to a reduction of negative mood, while the rest of the patients also demonstrate a reduction of pain and fatigue. It is worth mentioning that psychologically based interventions, have been proven to be useful when they are compared to no treatment or treatment other than aerobic exercise ¹⁰⁶. Preliminary data from functional MRI studies suggest that cognitive-behavioral therapies have the ability to restore the alterations in the functional connectivity of brain areas responsible for pain processing observed in fibromyalgia patients ¹⁰⁷.

Acupuncture

Acupuncture is the insertion of needles in the human body. There are different styles of acupuncture depending on the location and the depth the needles are inserted. The inserted needles can be stimulated by heat, electrical current (electro-acupuncture), mechanical pressure (acupressure), or laser (laser acupuncture). The most common type of acupuncture involves skin penetration without stimulation (manual acupuncture). Sham or fake acupuncture is a research tool to control the effects of real acupuncture. It can involve skin contact with the needles without actual penetration or needle insertion in areas other than the ones usually targeted.

In a high-quality meta-analysis, it was demonstrated that the effects of manual acupuncture on pain, sleep quality and global well-being did not differ significantly from the effects of sham acupuncture. On the contrary electro-acupuncture significantly reduced pain, fatigue and stiffness, while it improved sleep quality and global well-being when compared to sham acupuncture. Additionally, electro-acupuncture significantly improved pain, stiffness and global well-being when compared to non-acupuncture. The beneficial effects of acupuncture could be observed at 1 month after treatment, but they were not maintained at 6-7 months ¹⁰⁸.

Alternative therapies

The effectiveness of meditative movement therapies (qigong, yoga, tai chi) on sleep and fatigue improvement and of hydrotherapy on pain reduction has been supported by some studies ¹⁰⁹. A number of other modalities has also been utilized for the treatment of fibromyalgia including biofeedback, chiropractic therapy, massage therapy, hypnotherapy, guided imagery, electrothermal therapy, phototherapeutic therapy, music therapy, journaling / storytelling, static magnet therapy, transcutaneous electrical nerve stimulation and transcranial direct current stimulation. However there are no well-designed studies to advocate their general use ⁹⁹.

Massage therapy

In massage therapy, a massage therapist rubs and kneads the soft tissues of your body. The soft tissues include muscle, connective tissue, tendons, ligaments and skin. The massage therapist varies the amount of pressure and movement. Massage can reduce your heart rate, relax your muscles, improve range of motion in your joints and increase production of your body’s natural painkillers. It often helps relieve stress and anxiety.

Yoga and tai chi

Yoga and tai chi combine meditation, slow movements, deep breathing and relaxation. Both have been found to be helpful in controlling fibromyalgia symptoms.

Chiropractic adjustment

Chiropractic adjustment is a procedure in which trained specialists (chiropractors) use their hands or a small instrument to apply a controlled, sudden force to a spinal joint. The goal of this procedure, also known as spinal manipulation, is to improve spinal motion and improve your body’s physical function.

Aromatherapy

Aromatherapy or the therapeutic use of essential oils extracted from plants. Aromatherapy is thought to work by stimulating smell receptors in your nose, which then send messages through your nervous system to the limbic system — the part of your brain that controls emotions. Aromatherapy might have health benefits, including:

• Relief from anxiety and depression.
• Improved quality of life, particularly for people with chronic health conditions.

Physical therapy

A physical therapist can teach you exercises that will improve your strength, flexibility and stamina. Water-based exercises might be particularly helpful.

Occupational therapy

An occupational therapist can help you make adjustments to your work area or the way you perform certain tasks that will cause less stress on your body.

Counseling

Talking with a counselor can help strengthen your belief in your abilities and teach you strategies for dealing with stressful situations.

Recognize stress and take steps to reduce it

Because stress makes the symptoms of fibromyalgia worse, it’s important to recognize when you’re feeling stressed. Signs of stress may include a feeling of tension in your shoulders or neck, an upset stomach, or a headache. Unfortunately, there isn’t a way to completely get rid of stress in your life. However, you can focus on changing the way you react to stress. For example, you might set aside time each day to practice deep-breathing techniques or meditation.

Relaxation

If you have fibromyalgia, it’s important to regularly take time to relax or practice relaxation techniques. Stress can make your symptoms worse or cause them to flare up more often. It could also increase your chances of developing depression.

There are many relaxation aids available, including books, tapes and courses, although deep-breathing techniques or meditation may be just as effective. Try to find time each day to do something that relaxes you. Taking time to relax before bed may also help you sleep better at night.

Talking therapies, such as counseling, can also be helpful in combating stress and learning to deal with it effectively. Your doctor may recommend you try this as part of your treatment.

Establish healthy sleep habits

Lack of sleep can make your fibromyalgia symptoms worse. And increased pain makes it hard to get restful sleep. To avoid getting caught in this cycle, try to have healthy sleeping habits. Avoid caffeine and alcohol before bedtime, go to bed and wake up at the same time each day (including weekends), and limit naps during the day.

Fibromyalgia can make it difficult to fall asleep or stay asleep (known as insomnia). If you have problems sleeping, it may help to:

• get up at the same time every morning
• try to relax at least 1 hour before going to bed
• try to create a bedtime routine, such as taking a bath and drinking a warm, milky drink every night
• avoid caffeine, nicotine and alcohol before going to bed
• avoid eating a heavy meal late at night
• make sure your bedroom is a comfortable temperature, and is quiet and dark – use thick curtains, blinds, an eye mask or ear plugs
• exercise regularly during the day
  make sure your mattress, pillows and covers are comfortable
• avoid checking the time throughout the night

Everyone needs different amounts of sleep. On average we need:

• adults – 7 to 9 hours
• children – 9 to 13 hours
• toddlers and babies – 12 to 17 hours

You probably don’t get enough sleep if you’re constantly tired during the day.

Get into a routine

Many people who have fibromyalgia do better when their schedule follows a routine pattern. This usually means that each day they have meals at the same times, go to bed and get up at the same times, and exercise at the same time. Try to keep your weekend and holiday schedules as similar to your weekday schedule as possible.

Make healthy lifestyle choices

By making healthy choices, you’ll have more energy, you’ll feel better, and you’ll lower your risk for other health problems. Eat a healthy, balanced diet. Limit the amount of alcohol you drink. If you use tobacco products, stop. Lose weight if you are overweight.

Medications

A wide range of drugs has been used in the treatment of fibromyalgia including antidepressants, sedatives, muscle relaxants and antiepileptic drugs. The choice of medication is influenced by patient preference; prominence of particular symptoms, including fatigue, insomnia, and depression; potential adverse effects; patient tolerance of individual medications; cost and regulatory limitations on prescription choice ¹¹⁰. Nonsteroidal anti-inflammatory drugs and opioids, although often prescribed for fibromyalgia, are not an effective form of treatment ¹¹¹.

Three medications are specifically approved to treat fibromyalgia. Duloxetine (Cymbalta) and milnacipran(Savella) work by changing the levels of certain chemicals in the brain that help control pain. Pregabalin (Lyrica) targets brain chemicals that affect how much pain you experience. Duloxetine (Cymbalta) and milnacipran (Savella) may help ease the pain and fatigue associated with fibromyalgia. Your doctor may prescribe amitriptyline or the muscle relaxant cyclobenzaprine to help promote sleep.

Other medications can be used to treat pain, sleep and mood. These include anti-inflammatories, antidepressants and sleep medicines.

Anti-seizure medications designed to treat epilepsy are often useful in reducing certain types of pain. Gabapentin (Neurontin) is sometimes helpful in reducing fibromyalgia symptoms, while pregabalin (Lyrica) was the first drug approved by the Food and Drug Administration to treat fibromyalgia.

Patients should be informed that for most pharmacologic therapies several weeks may be needed until they experience a benefit. Initially a single drug should be administered. However, in the case of non-responsiveness combination therapy should be considered. Since therapeutic responses are rarely durable, physicians should not be surprised when the initial efficacy of a medication is abolished. Successful treatment of fibromyalgia may require regular reassessment and possible rotation of medications ¹¹². The doses of the most commonly used medications with strong and moderate evidence of effectiveness are shown in Table 4. Adequate dose prescription and patient adherence are significant for the effectiveness and tolerability of pharmacologic treatment ¹¹³.

Table 4. The doses of the most commonly used medications with strong and moderate evidence of effectiveness in fibromyalgia

The U.S. Food and Drug Administration has approved three drugs for the treatment of fibromyalgia. In June 2007, Lyrica (pregabalin) became the first FDA-approved drug for specifically treating fibromyalgia; a year later, in June 2008, Cymbalta (duloxetine hydrochloride) became the second; and in January 2009, Savella (milnacipran HCI) became the third ¹¹⁴. Older drugs that affect these same brain chemicals also may be used to treat fibromyalgia. These include amitriptyline (Elavil) and cyclobenzaprine (Flexeril). Other antidepressant drugs can be helpful in some patients. Side effects vary by the drug. Ask your doctor about the risks and benefits of your medicine.

Lyrica, Cymbalta and Savella reduce pain and improve function in some people with fibromyalgia. While those with fibromyalgia have been shown to experience pain differently from other people, the mechanism by which these drugs produce their effects is unknown. There is data suggesting that these drugs affect the release of neurotransmitters in the brain. Neurotransmitters are chemicals that transmit signals from one neuron to another. Treatment with Lyrica, Cymbalta, and Savella may reduce the level of pain experienced by some people with fibromyalgia.

Lyrica, marketed by Pfizer Inc., was previously approved to treat seizures, as well as pain from damaged nerves that can happen in people with diabetes (diabetic peripheral neuropathy) and in those who develop pain following the rash of shingles. Side effects of Lyrica including sleepiness, dizziness, blurry vision, weight gain, trouble concentrating, swelling of the hands and feet, and dry mouth. Allergic reactions, although rare, can occur.

Cymbalta, marketed by Eli Lilly and Co., was previously approved to treat depression, anxiety, and diabetic peripheral neuropathy. Cymbalta’s side effects include nausea, dry mouth, sleepiness, constipation, decreased appetite, and increased sweating. Like some other antidepressants, Cymbalta may increase the risk of suicidal thinking and behavior in people who take the drug for depression. Some people with fibromyalgia also experience depression.

Savella, marketed by Forest Pharmaceuticals, Inc., is the first drug introduced primarily for treating fibromyalgia. Savella is not used to treat depression in the United States, but acts like medicines that are used to treat depression (antidepressants) and other mental disorders. Antidepressants may increase suicidal thoughts or actions in some people. Side effects include nausea, constipation, dizziness, insomnia, excessive sweating, vomiting, palpitations or increased heart rate, dry mouth and high blood pressure.

Studies of both drugs showed that a substantial number of people with fibromyalgia received good pain relief, but there were others who didn’t benefit.

Lyrica and Cymbalta are approved for use in adults 18 years and older ¹¹⁴. The drug manufacturers have agreed to study their drugs in children with fibromyalgia and in breastfeeding women.

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) are often used as initial treatment for fibromyalgia. Their analgesic effect is independent of their antidepressant action and is thought to be mediated by inhibition of norepinephrine (rather than serotonin) reuptake at spinal dorsal horn synapses, with secondary activity at the sodium channels. The most widely studied drugs of this group are amitriptyline and cyclobenzaprine. They should be administered at lower doses than those required for the treatment of depression, a few hours before bedtime, and their dose should be escalated very slowly. A clinically important improvement is observed in 25-45% of patients treated with TCAs compared to 20% in those taking placebo ¹¹⁵. However their use is limited by the fact that they are ineffective or intolerable in 60-70% of patients ¹⁰⁵, while their efficacy may decrease over time ¹¹⁶.

In a systematic review and meta-analysis, amitriptyline was shown to be more efficient compared to the serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran in reducing pain, sleep disturbance, and fatigue, without differences in acceptability ¹¹⁷. The combination of 20 mg of fluoxetine in the morning with 25 mg of amitriptyline at bedtime has been shown to be more effective than either medication alone ¹¹⁸. Side effects of amitriptyline include dry mouth, constipation, fluid retention, weight gain, grogginess, difficulty in concentrating and possibly cardiotoxicity.

Cyclobenzaprine has a similar tricyclic structure and presumed mode of action with amitriptyline in fibromyalgia, but is thought to have minimal antidepressant effect ¹¹⁰. A meta-analysis of five placebo-controlled trials has revealed improvement of the global functioning, with a similar effect size as this reported for amitriptyline. The group that received cyclobenzaprine had a significant decrease in pain for 4 weeks, compared to those treated with placebo, but the decrease in pain was not significantly different after 8 and 12 weeks. Sleep was improved at all time points in both cyclobenzaprine and placebo groups, while no effect was noted on fatigue ¹¹⁵. It has been demonstrated that the use of very low-dose cyclobenzaprine (1 to 4 mg at bedtime) can improve the symptoms of fibromyalgia, including pain, fatigue, and depression, compared to symptoms at baseline and to placebo. Significantly more patients who received the very low-dose of cyclobenzaprine experienced improved restorative sleep, based upon analysis of cyclic alternating pattern of sleep by electroencephalography. The increase in nights with improved sleep by this measure correlated with improvements in fatigue and depression ¹¹⁹.

Desipramine has fewer anticholinergic and sedative effects than other tricyclic antidepressants, which can make it a possible alternative, although its efficacy is not well studied in fibromyalgia.

Serotonin-norepinephrine reuptake inhibitors

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are similar to tricyclic antidepressants in their ability to inhibit the reuptake of both serotonin and norepinephrine, but they differ from tricyclic antidepressants in being devoid of significant activity at other receptor systems, resulting in diminished side effects and increased tolerance. Venlafaxine, duloxetine and milnacipran have been shown to be effective in diminishing fibromyalgia symptoms ¹²⁰. These drugs can be used in fibromyalgia patients who do not respond to a trial of low-dose tricyclic antidepressants or who have intolerable side effects. They can also be administered as an alternative to amitriptyline for initial therapy. Of these medications’ duloxetine and milnacipran are better studied and they are preferred to be administered to patients with fibromyalgia. There are more limited data regarding the efficacy of venlafaxine for fibromyalgia, while withdrawal symptoms if a dose is missed occur more often, because of the short half-life of this medication ¹²¹. A meta-analysis has shown that fibromyalgia patients treated with duloxetine at 60mg daily are more likely to have more than 50% reduction in pain, compared to patients taking placebo ¹²². However, duloxetine at 30mg daily does not significantly reduce pain ¹²³. The efficacy of duloxetine can be maintained at 3 and 6 months of treatment ¹²⁴. In a 2018 systematic review and meta-analysis it was shown that duloxetine and milnacipran were not superior to placebo in the frequency of pain relief of at least 50%, but there was a benefit in reducing the pain at least by 30% and in the patient’s global impression to be much or very much improved. Additionally, there was not a significant difference in the reduction of fatigue, in the reduction of sleep problems, nor in the improvement of health-related quality of life ¹²⁵. Another meta-analysis has shown that duloxetine, pregabalin and milnacipran were superior to placebo for pain relief, while duloxetine and pregabalin were superior to milnacipran. These drugs also differed in their effects on sleep disturbances, depression and fatigue. Headaches, nausea and diarrhea were more common with duloxetine and milnacipran treatment, while cognitive defects and weight gain were more common with pregabalin ¹²⁶.

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors block the catabolism of serotonin, increasing its levels in the brain. It has been indicated that pirlindole and moclobemide have a significant beneficial effect on pain, without a significant effect on sleep nor fatigue ¹²⁷.

Anticonvulsants

Pregabalin has been reported to be efficient against pain, sleep disturbances and fatigue in fibromyalgia. In a meta-analysis a reduction of pain of at least 50% was found in 22% of patients treated with pregabalin, compared to 14% of those taking placebo. There was a small benefit in sleep disturbances, while no improvement could be found on fatigue ¹²⁸. Side effects such as somnolence and dizziness have been reported ¹¹¹. It is preferred in patients with more severe problems with sleep, and it is administered at bedtime.

Gabapentin has been shown to be efficient in treating fibromyalgia associated pain, while it was well tolerated ¹²⁹. Side effects include dizziness, sedation, lightheadedness, and weight gain. It can be considered as an acceptable alternative in case pregabalin cannot be administered due to its cost or due to regulatory limitations.

Muscle relaxants

Carisoprodol in combination with acetaminophen and caffeine has been shown to improve pain, sleep quality and the overall feeling of well-being in fibromyalgia patients ¹³⁰.

Sedative hypnotic agents

Zopiclone and zolpidem have been used in fibromyalgia. It has been suggested that they can improve the sleep and perhaps fatigue, without any significant effects on pain ¹⁰⁵.

Sodium oxibate, a precursor of GABA with powerful sedative properties has been shown to improve pain, fatigue and sleep architecture in fibromyalgia ¹³¹. However, in view of safety concerns the European Medicines Agency and the US Food and Drug Administration have not approved it for use in fibromyalgia patients.

Tramadol

Tramadol has multiple analgesic effects, since it inhibits norepinephrine and serotonin reuptake, and its major metabolite binds weakly to opioid μ receptors ¹⁰⁵. The use of tramadol (with or without acetaminophen) is both effective and well tolerated for the management of pain in fibromyalgia ¹³². There are some concerns regarding the long-term potential of abuse of tramadol, although the risk is less than that of more potent narcotic analgesics that have also been used in fibromyalgia.

Other treatment options

As well as medication, there are other treatment options that can be used to help cope with the pain of fibromyalgia, such as:

• swimming, sitting or exercising in a heated pool or warm water (known as hydrotherapy or balneotherapy)
• an individually tailored exercise programme
• cognitive behavioral therapy (CBT) – a talking therapy that aims to change the way you think about things, so you can tackle problems more positively
• psychotherapy – a talking therapy that helps you understand and deal with your thoughts and feelings
• relaxation techniques
• psychological support – any kind of counseling or support group that helps you deal with issues caused by fibromyalgia

See self-help for fibromyalgia for more information about exercise and relaxation techniques.

Treating other conditions

If you’ve been diagnosed with fibromyalgia and another condition, such as depression or irritable bowel syndrome (IBS), you may need to have separate treatment for these. For example, additional counseling or medication may be recommended.

Fibromyalgia diet

Some people say their fibromyalgia symptoms are worsened by certain foods or food additives — such as refined flour, dairy products, sugar, sugar substitutes or MSG — but there’s no clear research-based evidence to support this. Fibromyalgia patients produce higher levels of harmful free radicals than healthy people and have a decreased antioxidant ability, contributing to oxidative stress ¹³³.

Some studies show a benefit in avoiding certain foods or additives, while other studies don’t show such a correlation. Scientists are investigating possible connections between the consumption of gluten and fibromyalgia symptoms, but more research is needed.

People who have fibromyalgia are also more likely to be overweight or obese, and both problems impact quality of life. For some people, losing weight can help reduce fibromyalgia symptoms.

The progression of fibromyalgia may be dependent on increased reactive oxygen species (ROS). Reactive oxygen species (ROS) are highly reactive chemicals, containing oxygen, that react easily with other molecules, resulting in potentially damaging modifications. Treatment with antioxidants and vitamins, in addition to antidepressants and structural analogs of gamma-aminobutyric acid (GABA), was able to change the symptoms of fibromyalgia patients ¹³⁴. Certain groups of bioactive compounds derived from medicinal plants have also demonstrated analgesic activity and antioxidant properties with respect to fibromyalgia: these include essential oils ¹³⁵, extracts ¹³⁶, monoterpenes ¹³⁷, sesquiterpenes ¹³⁸ and alkaloids ¹³⁹.

Table 5. Compounds with antioxidant and analgesic properties for fibromyalgia management

Living with fibromyalgia syndrome

There are many things you can do to while living with fibromyalgia, including:

• Getting enough sleep.
• Exercising.
• Adjusting your work demands.
• Eating well.

Getting enough sleep

Getting enough sleep and the right kind of sleep can help ease the pain and fatigue of fibromyalgia. You may have problems such as pain, restless legs syndrome, or brainwave changes that interfere with restful sleep. It is important to discuss any sleep problems with your doctor, who can prescribe or recommend treatment.

Tips for good sleep

• Keep regular sleep habits. Try to get to bed and wake up at the same time every day.
• Avoid caffeine and alcohol in the late afternoon and evening. Even though alcohol can make you feel sleepy, drinking any close to bedtime can disturb your sleep.
• Time your exercise. Regular daytime exercise can help improve your nighttime sleep. However, exercise within 3 hours of bedtime can keep you awake.
• Avoid daytime naps. Sleeping in the afternoon can interfere with nighttime sleep. If you feel like you cannot get by without a nap, set an alarm for 1 hour. When it goes off, get up and start moving.
• Reserve your bed for sleeping. Watching TV, reading, or using a laptop or phone in bed can keep you awake.
• Keep your bedroom comfortable. Try to keep your bedroom dark, quiet, and cool.
• Avoid drinking liquids and eating spicy meals before bed. Heartburn and late-night trips to the bathroom can interfere with your sleep.
• Wind down before bed. Avoid working right up to bedtime. Try some relaxing activities that get you ready for sleep, such as listening to soft music or taking a warm bath.

Exercising

Although pain and fatigue may make exercise and daily activities difficult, it is important for you to be as physically active as possible. Research shows that regular exercise is one of the most useful treatments for fibromyalgia. If you have too much pain or fatigue to do exercise, you should begin with walking or other gentle exercise. Over time you can build your strength.

Adjusting your work life

You can continue to work when you have fibromyalgia, but may have to make some changes to do so. For example, you may need to cut down the number of hours they work, switch to a less demanding job, or adapt your current job. An occupational therapist can help you make changes at work. For example, they can help design a more comfortable workstation or find more efficient and less painful ways to lift.

Eating well

Although some people with fibromyalgia report feeling better when they eat or avoid certain foods, no specific diet has been proven to influence fibromyalgia. Of course, it is important to have a healthy, balanced diet. Not only will proper nutrition give you more energy and make you generally feel better, it will also help you avoid other health problems.

Fibromyalgia diet

Some people say their fibromyalgia symptoms are worsened by certain foods or food additives — such as refined flour, dairy products, sugar, sugar substitutes or MSG — but there’s no clear research-based evidence to support this.

Some studies show a benefit in avoiding certain foods or additives, while other studies don’t show such a correlation. Scientists are investigating possible connections between the consumption of gluten and fibromyalgia symptoms, but more research is needed.

People who have fibromyalgia are also more likely to be overweight or obese, and both problems impact quality of life. For some people, losing weight can help reduce fibromyalgia symptoms.

Fibromyalgia syndrome prognosis

Most longitudinal long-term studies have shown that most fibromyalgia patients continue to have chronic pain and fatigue, but the majority of these studies have been from tertiary referral centers ¹⁵⁶. In contrast, patients treated by primary care physicians in the community have a much better prognosis ¹⁵⁶. Many demographic and psychosocial factors significantly impact the prognosis and outcome in patients with fibromyalgia. Female gender, low socioeconomic status, unemployment, obesity, depression, and history of abuse had negative effects on the outcome ¹⁵⁶.

Overall fibromyalgia prognosis is poor for many patients. Factors associated with poor prognosis include:

• A long duration of disease
• High-stress levels
• Presence of depression or anxiety that has not been adequately treated
• Long-standing avoidance of work
• Alcohol or drug dependence
• Moderate to severe functional impairment

Patients with fibromyalgia are more likely to be hospitalized for any reason compared to the general population.

Chronic pain causes

The cause of chronic pain is multifactorial and complex and still is poorly understood ¹⁵⁷, ¹⁵⁸, ¹⁵⁹, ⁴. 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 ¹⁶⁰. 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 ¹⁶¹.

The most common causes of chronic pain include ¹⁰:

• 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 ¹⁶², ¹⁶³. 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 ¹⁶², ¹⁶⁴.

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 ¹⁶⁵. 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 ¹⁶⁶. Despite its short-term pain relief benefits, tobacco smoking is associated with chronic pain intensity and prevalence in the long run ¹⁶⁷, ¹⁶⁶, ¹⁶⁸, ¹⁶⁹. 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 ¹⁶⁵.

Smoking status in individuals with chronic pain is also associated with alcohol-drug and opioid dependence ¹⁷⁰, ¹⁷¹. 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 ¹⁷². Furthermore, it is worth noting that alcohol initially has an acute pain relieving effect ¹⁷³, ¹⁷⁴, which can elevate the risk of alcohol abuse in individuals with chronic pain ¹⁷³, ¹⁷⁵.

Recent studies have shown that chronic pain patients with high levels of pain catastrophizing are more likely to engage in heavy drinking ¹⁷⁶.

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 ¹⁷⁷, 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 ¹⁷⁸ 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” ¹, ², ³, ⁴, ⁵.

The most common symptoms of chronic pain include ¹⁰:

• 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 complications

Chronic pain syndrome can affect patients in various ways. Major effects in the patient’s life are depressed mood, poor-quality or nonrestorative sleep, fatigue, reduced activity and libido, excessive use of drugs and alcohol, dependent behavior, and disability out of proportion with impairment ¹⁷⁹.

Chronic pain may lead to prolonged physical suffering, marital or family problems, loss of employment, and various adverse medical reactions from long-term therapy ¹⁸⁰.

Parental chronic pain increases the risk of internalizing symptoms, including anxiety and depression, in adolescents ¹⁸¹.

A study by van Tilburg et al ¹⁸² indicates that adolescents who have chronic pain and depressive thoughts are at increased risk for suicide ideation and attempt.

Complication rates for spinal cord stimulators are high, ranging from 5% up to 40% ¹⁸³, ¹⁸⁴. Most commonly, lead migration occurs, causing inadequate pain relief and requiring revision surgery and anchoring ¹⁸⁵, ¹⁸⁶. Lead movement often occurs in the cervical region of the spinal cord, given an increased range of motion of the cervical vertebra ¹⁸⁷, ¹⁸⁸. Spinal cord stimulator lead fracture can occur in up to 9% of placements ¹⁸⁹, ¹⁹⁰. Seromas are also very common and may require surgical incision and drainage ¹⁸³, ¹⁹¹. The risk of infection following a spinal cord stimulator placement is between 2.5% and 12% ¹⁹², ¹⁹³. 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 ¹⁹¹, ¹⁹⁴, ¹⁹⁵. 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% ¹⁹⁶.

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 ¹⁹⁷, ¹⁹⁸. 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 ¹⁹⁹. 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 ²⁰⁰.

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 ²⁰¹ 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 ²⁰² 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 ²⁰³ 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 6. Chronic Pain Treatment Options

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 ²⁰⁵, ²⁰⁶, ²⁰⁷, ²⁰⁸. The more debilitating the pain, the lower the engagement in physical activity ²⁰⁹.

People who have chronic pain are advised to stay physically active and get regular exercise ²¹⁰, ²¹¹. According to the available evidence, physical activity did not cause harm in people with chronic pain ²¹¹. 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” ²¹²:

• 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 ²¹³. Poor dietary habits can be considered as adverse lifestyle factors that partly account for the observed excess mortality among people with chronic pain ²¹⁴, ²¹⁵. Research indicates that the dietary quality of individuals with chronic pain tends to be lower than that of those without pain ²¹⁶, ²¹⁷, ²¹⁸. Evidence suggests that nutrition should be considered within a personalized approach to pain management ²¹⁹.

Collectively, unhealthy dietary patterns, overweight and obesity are increasingly acknowledged as viable targets for therapeutic intervention in individuals with chronic pain ²²⁰, ²²¹, ²²², ²²³, ²²⁴. Poor dietary habits often but not always relate to overweight or obesity ²²⁵. Meta-analyses confirm a positive association between overweight, obesity and low back pain ²²⁵, ²²⁶, ²²⁷, ²²⁸, ²²⁰, ²²¹, ²²⁹, with a higher body mass index (BMI) and fat mass correlating with increased prevalence of chronic pain ¹⁶⁷. 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 ²²¹. 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 ²²⁵. 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 ²²².

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 ²³⁰. In a more recent randomized controlled trial ²³¹, 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 ²³¹. However, when diet was combined with exercise, these reductions were less pronounced, although they remained significantly superior to the results achieved with exercise alone ²³¹. Additionally, it is worth noting that diet and exercise therapy, when integrated into standard care, have proven to be cost-effective for such patients ²³².

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 ²²⁴. This should involve the integration of behavioral changes to support and facilitate calories balance-related behavior ²³³. 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 ²³⁴. 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 ²¹⁹.

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 ²¹⁶. Additionally, preventing deficiencies in Vitamin D, Vitamin B12 and Magnesium has the potential to contribute to pain alleviation ²¹⁶, ²³⁵, ²³⁶. Lastly, ensuring sufficient fiber intake proves significant for promoting proper digestion, maintaining a healthy microbiome, managing weight and subsequently influencing chronic pain ²¹⁶.

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 ²³⁷ 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 ²³⁸, yoga, relaxation techniques, tai chi, massage, and osteopathic or spinal manipulation ²³⁹ 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 ²⁴⁰.
• 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 ²⁴¹, ²⁴². 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 ²⁴³. 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 7. Herbal Supplements used in Chronic Pain

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

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. Do not take more than the daily dose listed on the package. Speak to your doctor if acetaminophen (paracetamol) is not managing your pain.
• Non-steroidal anti-inflammatory drugs (NSAIDs) — medicines such as ibuprofen 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.
• Antidepressants — some medicines that are used to treat depression, such as amitriptyline, are also sometimes prescribed by doctors to reduce pain.
• Anticonvulsants or antiepileptic medicines — medicines that are commonly used to treat epilepsy can also help manage nerve pain. They include pregabalin and gabapentin.
• 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 ²⁴⁷. 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 ²⁴⁸, ²⁴⁹. 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 the opioids morphine, fentanyl, oxycodone or codeine, might be prescribed by a doctor for short periods of time, 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 ²⁵⁰. This is because opioids are proven to not be effective at treating chronic pain not caused by cancer.

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 ²⁵¹, ²⁵². Furthermore, liver toxicity can occur at therapeutic doses for patients diagnosed with chronic liver disease ²⁵³.

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 ²⁵⁴. 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 ²⁵⁵.

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 ²⁵⁶. 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 ¹⁸⁰. Additionally, there appears to be a dose-dependent risk of opioid overdose with increasing daily milligram morphine equivalents ¹⁸⁰.

Table 8. Chronic pain medications

Chronic pain prognosis

Many people with chronic pain can be helped if they understand all the causes of pain and the many and varied steps that can be taken to undo what chronic pain has done. Current chronic pain treatments can result in an estimated 30% decrease in a patient’s pain scores ²⁵⁷. A thirty percent reduction in a patient’s pain can significantly improve patients’ function and quality of life (QOL) ²⁵⁸. However, the long-term prognosis for patients with chronic pain demonstrates reduced function and quality of life ¹⁸⁰. Improved outcomes are possible in patients with chronic pain improves with the treatment of comorbid psychiatric illness ¹⁸⁰. Chronic pain increases patient morbidity and mortality, as well as increases rates of chronic disease and obesity ¹⁸⁰. Patients with chronic pain are also at a significantly increased risk for suicide compared to the regular population ¹⁸⁰.

Spinal cord stimulation results in inadequate pain relief in about 50% of patients ¹⁸⁰. Tolerance can also occur in up to 20 to 40 percent of patients. The effectiveness of the spinal cord stimulation decreases over time ²⁵⁹. Similarly, patients who develop chronic pain and are dependent on opioids often build tolerance over time. As the amount of morphine milligram equivalents increases, the patient’s morbidity and mortality also increase.

Ultimately, prevention is critical in the treatment of chronic pain ¹⁸⁰.

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