Fibromyalgia Syndrome and Myofascial Pain Syndrome

Tender Points

The anatomical location of the tenderness at the FMS tender points is deep to the skin in soft tissue structures such as skeletal muscles, ligaments, and bursae, but there is no convincing evidence that the painful tissues are histologically abnormal. According to the 1990 ACR RCC, at least 11 of the 18 tender points must exhibit painful sensitivity to 4 kg of digital palpation pressure. This amount of pressure can be standardized against an algometer, but a reasonably accurate clinical estimate of the correct amount of pressure can be obtained by pressing the examining thumb against an unyielding surface until blood flow in the thumbnail is blanched from its tip to its midportion.

The reliability of this examination as a measure of the pain threshold can be influenced by the amount of pressure applied and by the rate at which it is applied. The amount of perceived discomfort can be accentuated and prolonged by applying the stimulus repetitively to induce wind-up. Patients will often react to palpation of a tender point by withdrawal, diffuse activation of the erector pili of the skin (cutis anserina), or spontaneous lacrimation. The resultant local aching sensation at each examined tender point may persist for days. There is no role for the use of control points to exclude psychosomatic hysterical tenderness.

Clinical Assessment of Pain Severity

In the past it was common for research studies to document the total number of tender points at which 4 kg of digital pressure induced the perception of pain in FMS patients or in healthy normal controls (HNCs). Another examination-based approach was to determine the average pain threshold by averaging the individual pain thresholds of 18 tender points with an algometer. The lower than normal pain threshold in patients with FMS meets the established definition of allodynia, so FMS could properly be viewed as the human model of “chronic widespread allodynia.”

Clinical research studies designed to establish the severity of pain experienced by FMS patients now more commonly rely on subjective measurement of pain perception with validated questionnaire instruments. A simple pain visual analog scale (PVAS) anchored on the left by the term “no pain” and on the right by the term “severe pain” has been widely used for this purpose. Graded in millimeters from 0 to 100, the PVAS is considered to indicate mild pain with a score of less than 40 mm, whereas a score of 70 mm or greater is indicative of severe pain. It is common to exclude FMS patients from therapeutic trials when they report baseline PVAS values of less than 40 mm or greater than 90 mm. Most such studies found an average PVAS value at baseline of about 60 mm, and the goal of therapy was to reduce the severity of the pain by at least 30% (~18 mm) to achieve clinically relevant improvement ( ).

Pain

The most prominent feature, or clinical domain, of the FMS construct is chronic widespread pain. For years, people with FMS pain have been doubted, criticized, mocked, negated, and marginalized because of their unique condition of chronic widespread pain. One of the reasons for this reaction from health care providers, family, and friends has been that pain is common in the general population, at almost any age, so people who complained frequently about pain have been considered unduly sensitive, complainers, drug dependent, or seekers of secondary gain. No one can feel another’s pain, and medical science has never had an instrument that could document or objectify the severity of the pain experienced. The pain of FMS was and probably always will be subjective. On the other hand, the quest of a century of investigators to understand FMS has contributed uniquely to the scientific understanding of pain processing in general.

Patients with FMS were found to have a biologically based low pain threshold. With this widespread low pain threshold, patients with FMS met criteria for the term allodynia . This term is defined as pain that is induced by a stimulus that would not cause pain in an HNC ( ). Since the biological phenomenon of allodynia can be localized, regional, or widespread, it has been suggested that a new, more physiological name for FMS could be “chronic widespread allodynia” ( ). Some have said that people with FMS also exhibit hyperalgesia (defined as an abnormally exuberant response to a normally painful stimulus), but that assertion is impossible to prove because the presence of allodynia means that with any graded stimulus, pain is experienced by the FMS patient during each of many advancing steps before the “normally painful stimulus” level is achieved. To use a crude example, let us say that normal people report that heat applied to their forearm is painful at 120°F, but the scientist ignores that in an experimental testing paradigm. The scientist’s protocol is to ignore the test subject’s complaints of pain and continue to increase the heat until a temperature of 240°F is achieved. Should those doing the testing be surprised if the responses of the test subjects at that point are “abnormally exuberant”? One can imagine the test subjects saying “this has been painful for some time now, get this thing off my arm.” Allodynia means that affected persons might experience pain from a normal handshake, standing on their feet, sitting in a chair, or even lying on their bed when they awaken at night and perceive pain at areas of contact with the mattress.

It is now possible to objectively document allodynia by functional magnetic resonance imaging (fMRI), which was strategically applied to people with FMS ( , ). The results showed that FMS patients, as a group, did indeed experience the pain of which they complained and that it documented “objective allodynia” in these patients ( Fig. 48-5 ).

Recently, a committee of the American Academy of Pain Medicine proposed a simple, but rather intuitive new taxonomy for pain ( ). They suggested that pain which had a neurobiological basis be referred to as eudynia (nociceptive pain), Greek for “good pain,” whereas the term maldynia (maladaptive pain), Greek for “bad pain,” could be used for pain that typically occurs in the absence of ongoing noxious stimuli and does not promote healing and repair. This interesting new taxonomic approach to classifying pain is really stratified on the basis of a noxious versus a non-noxious stimulus rather than on the differential experience of the resultant pain. The exact magnitude of the stimulus that would distinguish these categories of stimuli might vary widely in different ethnic, gender, cultural, age, and diagnosis groups. This new taxonomy will be problematic for application to FMS patients, for whom the term maldynia seems to have been specifically designed. Patients with FMS cannot precisely distinguish the pain resulting from noxious versus non-noxious stimuli. For them, non-noxious and noxious stimuli are both amplified and both hurt. Therefore, they tend to react protectively to both, even when the stimulus is non-noxious and does not produce a lesion in need of healing or repair. The authors acknowledged that “the absolute clinical value of these definitions has not been established.”

Chronic Sleep Dysfunction

More than 90% of FMS patients experience chronic insomnia. Some have difficulty falling asleep, but most do not because they are exhausted by bedtime. The major problem with sleep in FMS is awakening after only a few hours of sleep and feeling distressingly alert and unable to sleep soundly again until near morning. People with FMS typically awaken in the morning feeling painfully stiff, cognitively sluggish, and non-refreshed by their sleep. It is surprising, then, that a person with such an overwhelming sleep deficit should have so much difficulty napping during the day. Patients appreciate learning about the disordered physiology of their sleep problem. observed an electroencephalographic (EEG) pattern of sleep architecture called alpha-wave intrusions in deep, delta-wave, non-rapid eye movement (NREM) sleep, which relates to subjective fatigue and psychological distress but is not specific for FMS. About 60% of patients with FMS exhibit this anomaly, whereas its prevalence was only about 25% in HNCs, insomniacs, and dysthymics ( ). Another EEG abnormality that has been evaluated in FMS is cyclic alternating patterns ( ). Of course, patients with FMS can also exhibit obstructive sleep apnea and periodic involuntary limb movements, which should be identified by polysomnography and treated separately.

There is a fairly direct connection between sleep dysfunction and body pain. An early study by disclosed evidence that the sleep dysfunction in FMS might be involved in pathogenesis of the pain. More recently, disclosed a mechanism by which sleep dysfunction and pain might be linked through altered descending inhibition of nociception ( Fig. 48-6 ). Thirty-two healthy adult women were studied polysomnographically for 7 nights. On nights 1–2 (baseline), all the study subjects slept undisturbed for 8 hours to adapt them to the laboratory environment. On nights 3–5, the study subjects were randomized into three intervention subgroups: to normal sleep (controls), to forced awakening every hour, or to delayed bedtime but then unaltered sleep. After each of the six experimental nights, the pressure pain threshold on the left arm was tested, followed by a right arm cold pressor test and retesting of the left arm pain threshold. The forced-awakening group demonstrated a significant loss of pain inhibition and an increase in spontaneous pain, whereas neither of the other two control groups showed changes in pain inhibition or spontaneous pain. The authors concluded that repeated “sleep interruption, but not simple sleep restriction, impairs endogenous pain-inhibitory function and increases spontaneous pain.” They believed that these findings support a pathophysiological role of sleep disturbance in the development of chronic pain. Another recent study ( ), using the cold pressor test has shown that descending inhibition is impaired in FMS and that the deficiency is statistically related to the FMS patients’ dysfunctional sleep.

More than 90% of FMS patients sleep so poorly that they are chronically sleep deprived. A FMS headache will often be due to insomnia and its consequences. Polysomnography is well justified in a patient with newly diagnosed FMS to facilitate a physiological diagnosis of the cause of the insomnia. Health care professionals should advise patients on how to improve their sleep hygiene, which may require taking the television out of the bedroom, using a red nightlight to avoid interfering with nocturnal melatonin production, and arranging for an alternate sleeping environment when the patient awakens because of a partner’s loud snoring. Shift work is very poorly tolerated by people with FMS, so the physician may need to assist them in changing a work schedule that is impossible for them to maintain.

Because of the chronic insomnia, it is very common for FMS patients to abuse coffee, tea, cola drinks, or other stimulants to help them feel alert during the day. Use of a morning or daytime stimulant can produce a vicious cycle because the stimulant that is taken for poor sleep will further interfere with the subsequent night’s rest. Typically, there is a perceived need for progressive escalation of the dosage of the stimulant over time. Failure to escalate the dosage—or certainly any relative decrease in the average daily dosage of caffeine—can precipitate a withdrawal headache.

A logical, but often strategically difficult solution to daytime tiredness is to take a short nap when tired rather than to take an oral stimulant in the form of a stimulant beverage. These patients should ultimately discontinue the use of all CNS stimulants. The non-steroidal drug naproxen, 500 mg twice daily for 2–3 days, will usually attenuate the head pain of a caffeine withdrawal headache but will not eliminate the subsequent desire to resume its use. As with tobacco habituation, there is a kind of comfort associated with sipping a flavored coffee while reading or visiting a friend. These habits will gradually lose their pull if the patient is convinced that the effort is worthwhile.

In addition to the potential health risks associated with the CNS stimulant compounds themselves, one must also be aware of the massive dosages of free sugar and dairy cream that accompany such beverages. The logical alternative chosen by many patients is one of the artificial sweeteners that are used regularly in popular diet sodas. Several recent studies have evaluated the effects of drinking diet cola on body weight ( , , , ), but their findings vary or are contradictory. A 2010 meeting of the British Nutritional Foundation explored the available data and concluded that “overall the evidence suggests that, despite partial caloric compensation, beverages sweetened with intense sweeteners can contribute to weight control” ( ). Of course, plain water would be at least as safe for people with FMS as the artificially sweetened beverages and would not contain the objectionable CNS stimulants.

Headache

Headache is a particularly troublesome form of regional pain. The World Health Organization has endorsed a study that reported the worldwide prevalence of headache in the general population to be 46% with a clear preference for females ( ). Of course, headache is not a single entity, but rather a generic term encompassing many kinds of head pain with many potential causes. Tension-type headache is much more common than the other types of headache. In the referenced study it was about fourfold more common than migraine ( ).

For years it was perceived that the headache of FMS was a tension-type headache involving the muscles of the neck, particularly the trapezius muscles, which merge with ligaments that attach to the occiput. The occipital nerves exited the occipital scull and penetrated these ligaments before fanning out bilaterally over each side of the scalp. The belief was that these nerves were sufficiently compromised by chronic tension on the ligaments to cause referred scalp pain. The pain feels like a band around the head with pressure behind both eyes and bilateral aching in the area of the occiput where exquisite tenderness to palpation was found and where unilateral local injection of an anesthetic agent would attenuate or eliminate the pain on the ipsilateral side. The most effective (more than any oral medication) conservative treatment of this form of headache in FMS patients was for affected individuals to take a long hot bath or shower and then to sleep for at least 30 minutes on their back with a small soft pillow supporting the neck.

More recently, headache nomenclature changed and the FMS headache fell in the category of “chronic daily headache” because its frequency was often in excess of 15 days per month for the previous 6 months. This new classification helped clarify the frequency of the FMS headache but did not change its underlying pathogenesis, identify any other cause, or dictate any change in its management.

Many clinicians have diagnosed migraine in FMS headache sufferers, principally because of the severity of the symptoms. Symptoms can include nausea but seldom progress to emesis. The pattern can be characterized by pain with movement of the head or with certain positions, especially with bending down so that the head is dependent. It can be associated with prominent sensitivity to sound and/or light. The problem with equating these dramatic clinical features with migraine is that people with FMS are typically sensitive to physical stimuli, bright light, and loud sounds even when they do not have what they would call a headache. Since FMS is an amplifier of neurological signals, these stimuli, which would not really bother an HNC, are noxious to persons with FMS and more so when they have an FMS headache. This could be interpreted as another manifestation of allodynia (see previous discussion of widespread pain above).

Features of an FMS headache that help distinguish it from migraine are the lack of a prodromal aura, lack of visual loss, lack of unilaterality, and lack of speech or language dysfunction in a postdrome. A possibly untoward consequence of identifying a FMS headache as migraine is that the typical response of health care providers to migraine is to treat it with a serotoninergic (triptan) medication. This class of medication might be helpful for the headache, but it might also induce the potentially lethal hyperserotonin syndrome in patients made more susceptible by their concomitant therapy with a drug such as a selective serotonin reuptake inhibitor (SSRI) or, more likely, one of the serotonin–norepinephrine reuptake inhibitor (SNRI) medications currently approved by the Food and Drug Administration (FDA) for the treatment of FMS pain.

If clinicians must consider a FMS headache diagnostically, differentially, and therapeutically, what factors should enter into their deliberations? It is clear that many forms of headache in adults can be induced by insomnia, by a variety of medications taken for other conditions, by dietary central nervous system (CNS) stimulants, by presbyopia, by giant cell arteritis, by MPS, by a variant of MPS involving the muscles of mastication in temporomandibular pain syndrome, or by allergy/infection-induced sinusitis. Depending on the differential diagnostic and manual medicinal skills of the primary care physician, it may be important to involve a variety of specialties in diagnosing and treating a patient with persistent, intractable FMS headache. The consultant list might include sleep physiology; neurology; physical medicine; ophthalmology; ear, nose, and throat; rheumatology; and dentistry.

Stiffness

The morning stiffness experienced by most FMS patients is remarkable because it is so severe and lasts so long. The typical stiffness of patients with inflammatory RA is 30 minutes to 2 hours, whereas that of OA is usually 5–15 minutes. By comparison, the stiffness of FMS patients is typically 45 minutes to 4 hours. The best clinical correlate with morning stiffness in FMS is pain, so patients may not be clearly distinguishing these seemingly different symptoms. Biochemically, the stiffness of RA correlates with the change in serum concentration of hyaluronic acid from early morning to noon in active individuals ( ). The same finding has been observed in FMS patients, thus suggesting that the biological association relevant to morning stiffness in both conditions may be the serum level of hyaluronic acid rather than inflammation.

Fatigue

About 80% of FMS patients complain of fatigue, and a subgroup meets the new criteria for chronic fatigue syndrome (CFS). The fatigue of CFS (a feeling of antimotivational exhausted weakness) is qualitatively and quantitatively different from that of FMS (a heavy feeling of tiredness). The differential diagnosis of fatigue is difficult because it must include a variety of sleep disorders, chronic infections, autoimmune disorders, psychiatric co-morbidities, and neoplasia. Fatigue may also result from sedating medication used to treat the insomnia of FMS, such as tricyclic antidepressant drugs.

Cognitive Dysfunction

Patients with FMS frequently complain about diminished cognitive function. This symptom ranges from difficulty concentrating when reading a book to short-term memory deficits. A research study suggested that FMS patients perform poorly on a range of cognitive tasks ( ), but evidence of abnormality is more apparent in the face of distraction or during multitasking experiments. Causes of cognitive dysfunction could include chronic pain, medications taken to control pain or sleep dysfunction, chronic loss of restorative sleep, or affective disturbances, but it cannot help to be rapidly losing brain cortical volume (see loss of gray matter, later).

Psychiatric Co-morbidity

Before FMS was better understood as a condition of central sensitization, patients with this condition were often suspected of having hypochondriasis, health-related phobia, or a mood disorder. There is a subgroup of FMS with associated depression or anxiety, but it is unlikely that an affective disorder is the cause of FMS. Indeed, two objective distinctions between FMS and major depression are that minor elevations of cerebrospinal fluid substance P levels in depression may be spurious ( ) and that patients with depression exhibit normal descending inhibition in response to the cold pressor test while that response is markedly impaired in FMS ( ). It is also interesting that the somatic manifestations of FMS are on a different statistical track than the psychiatric manifestations ( , ). The do not correlate with each other. The prevalence of depression in FMS at any point in time was reported to be 22% or 34%, utilizing different methodologies ( , ). If less than 40% of FMS patients were depressed at the time of diagnosis of FMS, more than 60% were not depressed. Depression also occurs with RA (20–30%), cancer, and other chronic conditions (14–33%), where the depression is considered to be an understandable consequence of the pain and physical limitation imposed by the underlying disease. The same is apparently true for FMS. It has been argued that FMS patients who have sought medical treatment are more likely to exhibit symptoms of depression than are those in the community who have not sought medical care ( ). Sexual abuse in childhood is no longer a viable hypothesis for the etiology of FMS ( ).

evaluated 78 FMS probands and 40 RA probands. These index cases led the investigators to 146 family members of the FMS probands and 72 family members of the RA probands. In both groups of families combined, the investigators found a total of 30 fibromyalgia patients. All of the FMS and non-FMS family members were subjected to psychiatric interviews to look for a lifetime prevalence of psychiatric disorders. The odds ratios (ORs) for people with FMS versus people without FMS to have exhibited a psychiatric disorder were as follows: bipolar disorder, OR = 153; major depression, OR = 2.7; any anxiety disorder (panic, post-traumatic stress disorder, obsessive–compulsive disorder, social phobias), OR = 6.7; an eating disorder (anorexia nervosa, bulimia nervosa), OR = 2.4; and a substance use disorder (no specific substance), OR = 3.3 (not associated with family members not affected by FMS).

The authors commented on the unexpectedly high prevalence of bipolar disorder and noted that this co-morbidity raised concern about the use of antidepressant medications, which could precipitate hypomanic, manic, or mixed reaction disorder in predisposed individuals, even though the bipolar condition had previously been latent. It clearly is important to identify bipolar disorder when it accompanies FMS because its presence would contraindicate the use of all antidepressant medications and even the SNRIs that are approved by the FDA for the treatment of FMS.

In the majority of the same authors’ co-morbid cases, the associated psychiatric disorders developed more than 1 year before the FMS became apparent. This observation raises the issue of selection bias in this study because the sources of the patients were the practices of several psychiatrists who would be involved in the care of patients with psychiatric disorders. They extensively address the issue of selection bias in their discussion and tried to discount it. Nonetheless, the high prevalence of bipolar disorder alone would strengthen the argument in favor of selection bias. The authors countered by proposing that fibromyalgia and certain psychiatric disorders may share pathophysiological links that might predispose them to the development of both types of conditions. The authors did not favor the development of FMS from psychiatric disorders or the reverse.

Myofascial Pain Syndrome

The frequency with which MPS is found in people with FMS depends on the criteria used and the examiner’s skill in finding trigger points. In part, the problem is that no clinical criteria are universally accepted for the diagnosis of MPS, as have existed for FMS over the past 20 years ( , , ). According to one skilled examiner, 72% of patients with FMS also have at least one active trigger point to suggest co-morbid MPS ( ). Another systematic screening of FMS patients for the signs and symptoms of MPS disclosed only 28% to have co-morbid MPS ( ). An unfortunate choice of FMS patients with co-morbid MPS as study subjects in one seminal study of the physiology of MPS further complicated the contemporary distinction between MPS and FMS ( ), but the same findings of spontaneous electrical activity disclosed by that study have been documented in the trigger points of MPS patients unassociated with FMS ( ). Clearly, there is overlap between FMS and MPS, but no convincing evidence suggests that a malignant spread of trigger points until they are widespread would adequately explain the development of FMS.

There is some intriguing objective data regarding the pathogenesis of MPS. Ultrasound imaging techniques have been used to distinguish the trigger points of MPS from normal tissue lacking trigger points ( ) ( Fig. 48-7 ). Adaptations of this methodology have enabled investigators to not only visualize the stiffened muscular tissue in the trigger point but also to show that the affected muscle tissue resists blood flow into it ( ). Other studies from the same group have used microdialysis to demonstrate that the microenvironment of the trigger point is more acidic (think ischemic with release of lactic acid from anaerobic glycolysis) than normal tissue. In addition, it contains increased concentrations of inflammatory and neuroactive chemicals, such as bradykinin, calcitonin gene–related peptide, substance P, tumor necrosis factor-α, interleukin-1β, serotonin, and norepinephrine ( ). It has been proposed that these changes result from local muscle ischemia, which prompts local release of inflammatory substances that may sensitize muscle nociceptors ( , ) ( Fig. 48-8 ).

Treatment of the symptoms of MPS focuses on eliminating the trigger point through local cold spray, needling with or without local anesthesia and ultrasound guidance, muscle conditioning, and posture training ( , ).