muscle pain syndrome(fm, mps)

[문형철]

Muscle Pain Syndromes

[Original Articles: Review & Analysis: Musculoskeletal]

Harden, R Norman MD

From the Center for Pain Studies, Rehabilitation Institute of Chicago, Chicago, Illinois.

All correspondence and requests for reprints should be addressed to R. Norman Harden, MD, Center for Pain Studies, Rehabilitation Institute of Chicago, 446 E. Ontario St, Suite 1011, Chicago, IL 60611.

A draft of this article was originally presented January 9–10, 2006, in Bethesda, Maryland, during the Musculoskeletal Research Conference jointly sponsored by the National Center for Medical Rehabilitation Research, the National Institute on Aging, the National Institute on Arthritis and Musculoskeletal Diseases, the Social Security Administration, and the Interagency Committee on Disability Research. There is no apparent conflict of interest related to the context of participation of the author of this article.

ABSTRACT

Harden RN: Muscle pain syndromes. Am J Phys Med Rehabil 2007;86(Suppl):S47–S58.

This article summarizes the evidence for two major clinical syndromes of muscle pain: fibromyalgia and myofascial pain syndrome. The evidence for diagnostic and treatment approaches is reviewed.

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Pain from muscle (and its surrounding fascial tissue) is one of the most frequent diagnoses seen in general practice and in pain clinics.1,2 References to pain resulting from palpable and tender areas in muscle began to be found in European medical literature in the early 1800s. Virchow coined the term “muscular rheumatism” in 1852 to describe palpable changes in muscle as a complication of rheumatic fever.3 In the early 1900s, Gowers discussed musculoskeletal pain in a variety of conditions, including lumbago, which he thought was caused by inflammation, and coined the term “fibrositis.”4 Stockman was concurrently discussing connective tissue hyperplasia, which came to be an early hypothetical pathophysiology of the fibrositic condition.5 Kellgren was the first to report referred pain during palpation of tender points in the muscle.6

In the latter part of the 20th century, with the superb work of Travel, Simons, and Gerwin on myofascial pain syndrome (MPS), the work of Wolfe, Yunus, and Bennett on fibromyalgia (FM), and the efforts of many others,7–10 clinicians began to entertain a distinction between these two muscle pain syndromes. Travel taught of a posttraumatic, regional pain disorder associated with painful areas which, when palpated, triggered a sensory phenomenon (referred pain) into anatomically distinct areas. Fibrositis, and later FM, was characterized as a more systemic process, often associated with sleep disruption and sometimes with affective diagnoses.11–13 Travel and Simons corroborated the distinction between the two syndromes although, to date, there is no formal criteria for making this diagnosis.7,8,14 FM passed through several temporary criteria 9,11,12,15–18 until 1990, when the American College of Rheumatology codified a formal taxonomy and diagnostic scheme to be used for epidemiology and research.10 Unfortunately, it has become common practice to use it as if it were a definitive diagnostic criteria. Currently, MPS is numerically the foremost primary muscle pain disorder,19 whereas FM is now thought to be part of a spectrum of diseases characterized by systemic symptoms, with the muscle pain (formally, “muscle tenderness”) probably representing a secondary manifestation of central sensitization.20–24

Muscle pain from rheumatologic causes (autoimmune processes, such as polymyalgia rheumatica) is preval‎ent and can be very disabling, but it is beyond the scope of this article, which will focus on nonrheumatologic muscle pain syndromes.

Diagnosis

A major impediment to the development of specific, distinguishing diagnostic criteria has been the ongoing debate over the validity of MPS and FM as bona fide syndromes, and over the extent to which MPS is distinct from FM.12,25–32 Despite continued and sometimes emotionally charged debate,15,27 numerous previous studies have suggested that there are two distinct entities in muscle pain: the systemic, hurt-all-over process FM and the more regional MPS.12,25,30,32 Results from a survey of practitioners in the American Pain Society show that 88% believe that MPS is a distinct, legitimate clinical entity, and 86% indicate that MPS is distinct from FM syndrome (FMS).19

The process of developing criteria for FM also has proven to be important in distinguishing it as a specific entity. Early proposals for diagnostic criteria for FM 11 stimulated increased study of the then-misunderstood and underresearched syndrome and led to increased acceptance of its clinical validity.9,16 This research eventually led to the development of formal, consensus-based diagnostic criteria, which were then subjected to experimental validation 17,18 and were ultimately officially endorsed by the American College of Rheumatology (ACR).10 Although there are problems with the ACR criteria,13,27,33 they have provided an important framework for communication and research regarding FM. The lack of such a widely accepted and criterion-based diagnostic scheme for MPS has been deleterious to clinical communication and research. Our MEDLINE review of the literature published since the classic Travell and Simons work 7 indicates no successful, comprehensive, consensus- or empirically based effort to determine clinically valid diagnostic criteria for MPS. Comprehensive efforts to develop these criteria, like those used in the case of FM, would likely facilitate communication and more generalizable research regarding MPS, and would ultimately lead to improved diagnostic accuracy and more precise treatments.34

Diagnosis of FM

The publication of the ACR criteria for diagnosing FM was a great step forward in our efforts to understand the syndrome. Unfortunately, the potential promise has never been fully realized, and there are many problems with the criteria.27,28 There is nothing that has proved to be specific about the 18 points selected, and this was simply the most recent scheme of several, all using other points. These points may be tender in normals and have not been shown to be externally valid (specific).13 The criteria are based on the patient's subjective response to a nonspecific stimulus,35 and a biased operator then must assess this response. There is no possible way to blind either the subject or the examiner, and the locations of the points are readily available to the lay public over the internet. The whole diagnostic system rests on the palpation of these 18 points 12,35 with finger pressure of approximately 4 lbs/cm²; of course, there are problems with inter-rater/examiner reliability.27,36,37 This situation has been helped some by the use of mechanical devices that quantitate this stimulus (the dolorimeter).37–39 To say the least, these criteria are subjective and nonspecific and are predictably quite controversial.27,28 This lack of specificity comes with many perils, particularly that of overdiagnosis. The less astute clinician may abandon the differential search for the many other causes of widespread pain prematurely (such as polymyalgia rheumatica, statin side effect, growth hormone deficiency, hypothyroidism, parasitic diseases, Lyme disease, to mention a few), with the obvious incumbent danger to the patient.40 The only prudent approach is that FM must remain a diagnosis of exclusion.

Now, a process of empirical validation of these criteria must occur. On the basis of experience in development of the International Headache Society criteria and psychiatric diagnoses by the Diagnostic and Statistical Manual, the starting point in the criteria development process should be to establish a broad clinical consensus regarding the signs and symptoms that comprise FM.36,41,42 The next step in this process is internal and external validation of the signs and symptoms designated as experimental FM diagnostic criteria.43–45

Internal validation uses statistical pattern recognition techniques, such as factor and cluster analysis, to examine interrelationships between signs and symptoms and can help guide criteria development.43,46 External validation of proposed criteria should also be conducted,42,43,46 focusing on the ability of proposed FM diagnostic criteria to discriminate between MPS and other nonmyofascial conditions (e.g., neuropathic conditions).

There is accumulating evidence that the points selected by the ACR are not specific and that considerably fewer points may be sufficient to make the diagnosis.47,48 Patients with FM have shown decreased perception threshold for cold pain,20,21,24 threshold for heat pain,20,21 tolerance for cold pain,20,21 heat pain tolerance,20,21 aberrations of cold perception,20 abnormal thermal windup and, after sensations,24 a decreased spinal nociceptive flexion reflex threshold,21 and an abnormal summation of mechanical stimuli.23 Gracely et al.22 also has shown evidence that there is augmentation in cortical and subcortical areas.22 Therefore, this research which suggests FM is a central sensitization disorder, as well as our work on the tender points, suggest that there is likely no need to test all 18 points.49 Perhaps a smaller number of points in all four quadrants would be sufficient to detect this central nociceptive sensitization syndrome with good sensitivity and specificity. Our research indicates that as few as three sites may provide enough information for differentiation with normal subjects. Petzke et al.48 reports that three paired sites may be sufficient. A logical starting point for future validation research may be a single representative point in each body quadrant.

FM was traditionally thought to primarily affect women, and it certainly is diagnosed more frequently in women than men. The preval‎ence occurs in a 9:1 female:male ratio.50 MPS probably occurs as often in men as in women if accounting for the slightly increased occupational hazard in men (i.e., heavy construction jobs).19

Research Critique

Although the establishment of the consensus-based diagnostic criteria greatly helped in improving and promoting research in FM, the subjective nature of the criterion for this diagnosis makes for potentially heterogeneous research populations and difficulty with identifying interventions that show statistical effect for the whole group, but that may work perfectly well for subsets. It is also disappointing that no other criterion (i.e., insomnia, depression) have been assessed, and that the ACR criteria has never been empirically validated.

Diagnosis of MPS

The idea that myofascial pain is a distinct pain syndrome was first formally recognized in the seminal work of Travell and Simons,7,8 and these authors' diagnostic guidelines based on identification of trigger points have been published. The Classification of Chronic Pain, published by the International Association for the Study of Pain's task force on taxonomy, provides no specific criteria for the diagnosis of MPS; rather, it offers the note that “diagnosis depends upon the demonstration of a trigger point (tender point) and reproduction of pain by maneuvers which place stress upon proximal structures or nerve roots.”51

As described by Travell and Simons,7,8,14,34 MPS is characterized by the presence of regional pain and the presence of defined, exquisitely painful trigger points in a taut band of muscle, which produce characteristic patterns of referred pain upon palpation and a local twitch response to mechanical stimulation or needling.6,7,14,26,32,34,52–54 Work regarding MPS by these and other authors has also described numerous other signs and symptoms as being common characteristics of the disorder (e.g., ropiness in muscle, weakness, spasticity etc.).16,28,32,34,53,55–58 Test procedures, such as pressure algometry, sedimentation rate, myoglobin levels, thermography, EMG testing, and response to trigger-point injections or spray-and-stretch treatment have been proposed as helpful in making the diagnosis of MPS.1,26,56,59–61

In the survey of MPS, there was some consensus regarding what characteristics are relevant to the diagnosis of MPS. The majority (>50%) of those pain specialists who responded to the survey endorsed regional pain, the presence of trigger points, and normal findings on neurological exam as essential characteristics of MPS. The first two of these were originally mentioned by Travell and Simons as crucial, and the ubiquity of these characteristics in the survey may in part reflect the profound influence of these classic teachings. Travell and Simons' work also suggests that these two primary MPS characteristics are related, with the regional pain largely reflecting trigger point referral patterns.7

Although the three signs mentioned previously were the only ones specifically endorsed by a majority of the sample as essential, there was much broader agreement regarding signs and symptoms that are considered relevant to MPS diagnosis (either essential or associated characteristics). In addition to the signs described previously, the presence of muscular tender points, taut bands, muscle ropiness or muscle nodules; dull, achy, or deep pain; decreased range of motion; and pain that is exacerbated by stress were agreed upon by more than 80% of the sample. These signs or symptoms can be assessed at the bedside without special procedures or equipment. More than 90% of respondents also considered positive response to injection of local anesthetic or spray and stretch to be an essential or associated characteristic of MPS.26,29,34

Various lines of research support 54,62 or fail to support 63 trigger point injections and/or spray and stretch as diagnostic tools. There are specificity problems in basing the diagnosis exclusively on the presence of trigger points; it can be difficult to distinguish between MPS and pain caused by other conditions,34,36,37,60 and it may be particularly difficult to differentiate between trigger points and the tender points of FM.13,37,64,65 Several lines of evidence suggest that there is very poor inter-rater or intrarater reliability in identifying trigger points.64–67

This reliability could be improved by training.64 The development of normative data and the use of mechanical pressure threshold meters have significantly improved the quantification of these tender/trigger points 37–39 but not their distinction. Developing clinical criteria in the absence of a known pathophysiology or a gold-standard laboratory test is challenging.46,68 At present, research suggests that spontaneous end plate noise on electromyographic examination may be a defining characteristic of myofascial trigger points, with no such noise noted in normal muscle or latent trigger points.14,60,69,70 Although these data strongly suggest that spontaneous end plate noise may ultimately prove to be a gold standard against which bedside diagnostic criteria for MPS can be validated, there is not yet total agreement on whether this characteristic pattern is necessary and sufficient to identify the trigger points of MPS. It is clear that endplate potentials are common in subjects with MPS in the affected muscles, but not exclusively so.71 The Rabbit Model of MPS is serving to better research this endplate noise as a potential diagnostic test.72 There is also some very interesting work sampling the micromilleu of the trigger points, with some potential utility from a diagnostic perspective.73 Shah et al.73 found that there was a significant elevation of inflammatory mediators (e.g., bradykinin), catecholamines (serotonin, norepinephrine), cytokines (tumor necrosis factor-alpha and interleukin-6 beta), and neuropeptides (substance P, calcitonin gene-related peptide) in trapezial trigger point of patients with MPS, vs. age- and sex-matched control subjects.

Consequently, there is not yet a consensus regarding a definitive/objective reference point (gold standard) for ensuring that any MPS diagnostic criteria are valid; however, the work of Simons and Shah hold promise in this regard, as well as the possibility of eventually elucidating the pathophysiology.74 As long as MPS is considered a syndrome, all relevant signs and symptoms should be included in any diagnostic criteria for the disorder. However, if an unequivocal pathophysiology of MPS is identified, then the disorder would no longer be a syndrome, and the name should be changed to reflect the specific pathophysiological mechanism accounting for the disorder.75 If the disorder proves to be a specific dysfunction of muscle alone (i.e., electrodiagnostic changes at endpoints in trigger points), then a separate diagnostic classification would need to be generated for pain syndromes involving fascial tissue (e.g., tendons, ligaments, scars). Furthermore, even if electrodiagnostic or biochemical abnormalities prove to be a gold standard for identifying MPS,14,60,69,70,73 there will always be an important need for bedside tests to identify patients appropriate to refer for confirm‎atory and perhaps expensive testing.

Although developing adequate diagnostic criteria in the absence of such a definitive reference point may be challenging, criteria for the diagnosis of headache (International Headache Society) and psychiatric disorders (Diagnostic and Statistical Manual IV) have been successfully developed within this same context.42,76 Therefore, even in the absence of a gold standard for MPS, it should be possible to develop clinically useful criteria for diagnosis of MPS. Additional research to validate such criteria will be necessary.14,34,43,44,77 If spontaneous endplate noise and spikes are proven to be the defining characteristic of MPS, this will greatly facilitate validation research.14,60,69,70 The emphasis should be on developing user-friendly criteria that can be easily applied at the bedside without any special equipment.

The most significant problem with the criteria is its complete reliance on a patient's subjective response to a nonspecific stimulus,78 which is assessed by a biased operator. The patient's response to palpation is probably influenced by many psychological and sociological factors.79,80 There is currently no viable method to blind either the subject or the examiner. In summary, these criteria are subjective, nonspecific, and are predictably quite controversial.81,82

Research Critique

Research in MPS and related musculoskeletal problems is essentially at a standstill because of the lack of common, standard diagnostic criteria. The process of survey consensus development, empirical validation, and reval‎idation are very clear.19 The passive acceptance of traditional, vague diagnostic schemes with no evidence base to support them is essentially the largest impediment to progress in this and all areas of pain research.

Treatment of FM

FM is a disorder characterized by widespread pain with point tenderness at defined areas and is often associated with sleep disturbance, fatigue, and morning stiffness.10 Although a variety of therapies have been proposed, empirical research indicates that the most effective therapies are consist of sedative therapy (analgesic serotonin/norepinephrine reuptake blockers),83 patient education,84 and aerobic exercise.78,85–88 Some patients can improve substantially just using these basic techniques, but the majority will need a more comprehensive rehabilitation approach.

Physical Therapy

Beginning with small, gentle active therapies by the patient, the physical therapist can help the patient begin to extend range of motion and flexibility through mostly active gentle activities.79,85 If the patient has kinesophobia,89–91 then cognitive behavioral techniques could be undertaken in conjunction with exercise to demonstrate to the patient that movement does not necessarily lead to entirely negative consequences.

Gradually increasing strength and flexibility to prepare for an aerobic program is the goal, and this is accomplished by a series of land and water exercises and devices (i.e., Swiss balls, Thera-Bands, etc.). The physical therapist is also actively involved at this stage in gait training and postural correction. Active, self-management techniques are the sine qua non of therapy. On the basis of our experience, electrostimulation modalities occasionally may have some use,92 whereas other passive techniques, such as ultrasound, diathermy, or massage are less effective and of no real lasting benefit.

Probably the single most important and effective therapy in FM is aerobic exercise. We recommend at least 20 mins of target heart rate (80% maximum) a day. It does not matter what type of exercise the patient chooses to achieve this aerobic state; often, the challenge is to encourage and motivate the patient to slowly reach this goal. A coordinated team approach is justified to help the patient through the inevitable discomfort, fatigue, and predictable setbacks. Mechanisms accounting for the effectiveness of aerobic conditioning are unclear, although several speculative mechanisms have been proposed.10 For example, one known effect of aerobic exercise is an increase in endogenous opioid activity.93 Enhanced endogenous opioid activity is associated with analgesia,94 and it is possible that this enhanced endogenous opioid activity may account for reduced FM symptoms after aerobic training.79 Other authors have proposed that aerobic conditioning may result in symptom improvements by increasing the resistance of muscles to potentially painful microtrauma from daily activity.88

Although studies have documented that patients with FM are deconditioned relative to nonpatient control subjects,95,96 no prospective studies have examined treatment-related changes in objective indices of aerobic conditioning as they relate to changes in FM symptoms. Although direct conditioning-related changes would seem to be the most parsimonious explanation for the effectiveness of conditioning-based treatment, an empirical test of this assumption is necessary to rule out the possibility that a factor other than conditioning may account for the observed changes.85

We conducted a study that eval‎uated the impact of a home-based aerobic conditioning program on symptoms of patients with FM and determined whether changes in symptoms were related to quantitatively assessed changes in aerobic conditioning and if patients were likely to benefit from a self-managed, home-based aerobic program. The aerobic conditioning program took place at the participants' homes, outdoors, or at a local fitness club at the discretion of the individual.

Twenty-six male and female sedentary individuals ages 25-59 yrs diagnosed with FM syndrome before baseline eval‎uation using the criteria established by the American College of Rheumatology 10 participated in an individualized 12-wk, home-based aerobic conditioning program promoting an ultimate goal of daily aerobic exercise of 20–30 mins at 70–80% estimated maximum heart rate. Subjects were eval‎uated at baseline and exit for physiologic level of aerobic conditioning (VO_2max), myalgic score (pain pressure threshold of FM tender points), pain ratings (McGill Pain Questionnaire–Short Form, Present Pain Intensity, Visual Analog Score), and a variety of psychometric tests.97–99

Patients who completed the 12-wk exercise program demonstrated an increase in aerobic conditioning and a decrease in pain measured by the McGill Pain Questionnaire–Short Form. Importantly, patients who were unable or unwilling to complete this aerobic conditioning program reported significantly greater pain and greater disability from pain at baseline than those who completed the program. Patients suffering from FM can experience decreased pain and physiologic benefits from an aerobic conditioning program; however, patients who are experiencing significant disability from their pain are not likely to maintain a home-based conditioning program and should consider a group program. The results for passive physical therapy techniques (massage, ultrasound, low velocity manipulation etc.) are not encouraging.

Occupational Therapy

The occupational therapist (OT) takes the lead in functional restoration and works closely with the patient to prepare for the all-important aerobic program. The OTs also begin with gentle active movements and preliminary desensitization techniques. Later, the OT will optimize ergonomics, gait, work, sleep, and play postures, and help strategize with the team over the hurdles to functional and aerobic activities.

Recreational Therapy

Often, the recreational therapist is the first clinician to be able to get the patient to move freely and with some pleasure. In the context of restoring the patient to a pastime or a game that they once enjoyed, it may be possible to break through the kinesophobia and deactivation that so often accompany FM. With assistive devices and creativity (such as coaching instead of competing, bike instead of run, etc.), a patient can sometimes break the ice and find enjoyment and socialization in previously lost or new recreational activities.

Vocational Rehabilitation

As the patient progresses, the OT can begin to work with the vocational rehabilitation (VR) specialist to begin to assess and simulate work activities, if VR is an issue. A thorough understanding of the previous job description and requirements and, occasionally, vocational testing and targeted retraining, are part of VR. Eventually, VR can provide work capacities and targeted work hardening and functional capacities assessment so that the patient may return to gainful employment, the ultimate functional restoration. It usually requires a methodical, informed, experienced, and organized team approach to understand and successfully manage the Byzantine social and medicolegal quagmires in which patients may find themselves. This effort is best orchestrated by VR.

Psychology

In some cases, psychological consultation is a critical component of treatment in FM and, in some patients, this may be essential to recovery. A high incidence of depression and anxiety is found in patients with the syndrome, and cognitive behavioral psychotherapy is the most effective psychological intervention for these diagnoses. What has been called kinesophobia 89,90,100,101 is an ongoing operant issue associated with negative reinforcement when patients perform particular movements. The patient finds that whenever they perform certain maneuvers they have pain (acutely or later), which acts as a powerful negative reinforcer for performing that movement again. This sets up operant patterns that avoid these painful movements and, eventually, this avoidance become behaviorally set. It is important to demonstrate to patients that the consequences of movement are not always totally negative or painful; this can be best accomplished with a combination of psychotherapy and PT.

We have learned that normalized movement is critical in the recovery of patients with FM, and a variety of movement therapies such as Feldenkrais or Alexander Techniques can be undertaken in the context of psychotherapy. Family therapy also can be quite important, with the basic approach of trying to change solicitous family members into coaches. Biofeedback, relaxation, guided imagery, coping skills, and a variety of cognitive behavioral techniques have all been useful in our clinics in managing chronic, complicated FM.102

Medications

There are many medications that have been reported helpful in FM, but few that have been tested in double-blind, randomized controlled trials. At this time, a balanced empirical approach using observation, considering possible mechanisms, and then using the best current information to treat those mechanisms is the most productive clinical approach.75 Although monotherapy is the ideal, in practice, rational polypharmacy often is used. This requires a knowledgeable assessment as to general mechanisms and the specific mechanisms in any case, then combining drugs that make sense together (i.e., a peripherally acting agent with a centrally acting agent). Two basic classes of medications should be entertained; drugs used for prophylaxis (used daily to reduce the intensity, duration, and frequency of the pain) and abortive drugs (rescue agents) for crisis management.

The prophylactic drug selected often will be determined by the presentation of the patient. For example, if a patient with FM presents with significant depression, anxiety, and/or insomnia, the clinician could choose a tricyclic antidepressant with significant analgesic, sedative, and anxiolytic properties as a drug of first choice. The tricyclic antidepressants are traditional and seem to be particularly effective in FM, and a meta-analysis of FM treatments reports “antidepressants resulted in improvements on physical status and self report of FM(S) symptom.”103 This is likely the result of the serotonergic properties of the drugs, normalizing the putative serotonin deficit in FM, and the sedative properties of the class, normalizing sleep patterns. It is necessary that good clinicians have several tricyclic/quadracyclic drugs in their repertoire as they have varied side effects, which sometimes can be used to the patients' advantage.81,82 Selective serotonin reuptake inhibitors have shown mixed results 104 but have been disappointing for patients with FM in our clinical experience. Certain newer antidepressant agents, such as venlafaxine and mirtazepine, may show some promise, and very selective serotonin agents such as tropisetron (5HT3 antagonist) are showing some early success.105

The antiepileptic compounds are some of the best studied drugs in neuropathic pain,106 but they have not been studied in patients with FM. Gabapentin has been studied in large randomized controlled trials in patients with postherpetic neuralgia and diabetic peripheral neuropathy.107,108 The mechanism of action in gabapentin may be of interest in patients with FM 80,109; however, it is not completely understood. It probably works primarily through enhancing natural gamma amino butyric acid systems in pain modulation, but it may also have some impact in suppressing excitatory amino acids such as glutamate, which may be associated with central sensitization.110 This may complement the effect of tricyclic antidepressants.

Skeletal muscle relaxants (SMRs) are a widely prescribed class of medications, but there is little succinct information about their pharmacology. They probably constitute an important component in the armamentarium of therapies for common conditions such as lower back pain, but are often prescribed in patients with FM with no evidence supporting this indication (see discussion that follows, under MPS treatment).

As analgesics, the nonsteroidal antiinflammatory drugs probably have some role in the management of FM.111 Certain drugs in this class may be more useful; these include ketoprofen, which has detectable antibradykinin and antiprostacyclin effects as well as the usual antiprostaglandin effect. COX-2 inhibitors have not been tested in patients with FM. Opioids may be useful, especially in the acute pain crises; however, they remain controversial in chronic pain management.112,113 We have used a strategy of administering nonopioid medications for prophylaxis and opioids only in crisis management. We often tie using opioid therapy to increasing function and can use an acute or subacute opioid protocol to allow the patient to begin to progress in nonpharmacologic therapies. Issues of tolerance and long-term toxicity are unresolved as yet,112,114 and there is concern that long-term opioid use may actually elicit allodynia and/or hyperpathia.115 The NMDA receptor antagonists (such as MK-801, ketamine, and dextromethorphan) have been considered for management of these effects but have proved to be too toxic for regular human use.

There are myriad other chemicals purported and hawked for the treatment of FM, such as nutraceuticals, homeopathic, and herbals. None have any evidence supporting their efficacy, and although most have low levels of toxicity, they can have a severely deleterious effect on our patients' bank accounts. Acupuncture and other complimentary techniques have never been properly studied.

The key to successful treatment of the patient with FM is a trained, coordinated, and experienced interdisciplinary team uaing a functional restoration approach with a strong emphasis on aerobic conditioning and daily exercise. Creativity, compassion, and flexibility are essential. Some patients benefit from aerobic exercise and improved sleep alone, but most require rational-polypharmacy pharmacotherapy, intensified psychotherapy, or other elements of interdisciplinary pain management to make substantial progress.

Research Critique

Some minimal progress has been made in developing an evidence-based treatment of FM, but it is likely that a diagnostic criteria based entirely on patient subjective report will not provide specific enough targets for effective outcomes research. The great challenge of developing and using statistical methods appropriate for analyzing interdisciplinary methodologies simultaneously is also a significant hurdle. Cross-lagged, time series, and hierarchical models are available and may hold the key; newer technologies must be assessed and validated. The difficulties using standard randomized placebo controlled trials, which are suitable for drug studies, will need to be revisited: for instance, in the long-term trials that are necessary to assess nondrug therapies such as aerobic exercise, is it practical or even ethical to maintain a nontreatment wing?

Treatment of MPS

The more regional, posttraumatic MPS is treated differently and may respond to more local and specific techniques. The key ideas are relief of pain and inflammation, prevention of further injury, reducing spasm, correcting abnormal postures, and improving circulation.

Physical Therapy

The physical therapist should take the lead in the treatment of MPS. Acutely, more passive techniques such as ice or iontophoresis may be used. The use of ultrasound was found to be as effective as trigger-point injections in one trial.116 Splinting should be very brief and gentle, and active range of motion should be maintained as soon as medically feasible. When the patient moves into the subacute phase and starts to develop symptoms that are more consistent with a diagnosis of MPS, identification of behaviors/activities predisposing to ongoing injury must be identified and corrected. Postural imbalances, kinetic chain dysfunction, weakness, and spasm are all important targets for treatment. Although self-management is key, hands-on techniques such as massage and myofascial release can be important in treating subacute MPS. These should be delivered in a time-limited fashion, with the patient's understanding that the goal is to move from passive to active therapies.

Other Disciplines

The role of OT is postural correction, ergonomics to avoid ongoing injury, and facilitation of the team goals. Psychology will target illness and maladaptive behaviors and often will work with VR to facilitate complete functional reintegration. Patients with MPS had higher scores for anxiety than depression,116 and appropriate cognitive behavioral therapy is traditional in most treatment centers. Therapeutic recreation and these other disciplines may have a role similar to that described previously for FM if the condition becomes more chronic. Low-level laser therapy has been used, but a meta-analysis “has no effect on pain in musculoskeletal syndromes.”117 Subsequently, a large open label trial was positive,118 so it is unclear whether this therapy has a role. Acupuncture often is mentioned for the treatment of MPS, but there is no compelling evidence as to its efficacy. One older large open-label trial of dry needling of the trigger point suggests efficacy.119 A later systematic review looked at 23 studies of which “no trials were of sufficient quality or design to test the efficacy of any needling technique beyond placebo in the treatment of myofascial pain. Eight of the 10 trials comparing injection of different substances and all seven higher-quality trials found that the effect was independent of the injected substance. All three trials that compared dry needling with injection found no difference in effect.”120

Medications

Nonsteroidal anti-inflammatory drugs have a prominent role in the management of MPS, particularly in those cases in which there is considerable inflammation.33,113,121–123 Certain drugs in this class may be more useful; these include ketoprofen, which has detectable antibradykinin and antiprostacyclin effects as well as the usual antiprostaglandin effect. COX-2 inhibitors have not been tested specifically in MPS but can be useful in patients who have contraindications to or cannot tolerate nonsteroidal anti-inflammatory drugs. With long-acting nonsteroidal anti-inflammatory drugs and COX-2 inhibitors, these medications can be considered for prophylaxis of chronic pain, but the side-effect profile/risk of long-term use must be considered. Steroids can be particularly useful in the early/acute phases of MPS, particularly when there is significant inflammation. A short, tapering course of steroids may be indicated; however, longer courses have a questionable risk-benefit ratio.

Skeletal muscle relaxants are a widely prescribed class of medications used presumably to treat muscle spasm, the resulting postural abnormalities, and discomfort. They are very frequently prescribed for MPS, but there is little succinct information about their pharmacology, mechanistic rationale, or indication. As a class, they are structurally and pharmacologically diverse. Most of the research on SMRs is elementary and very old (often before the obsession with evidence-based medicine came into play), and there is little likelihood of any substantial research forthcoming, as they are all generic. Although these older studies have failed to show any one SMR to have greater efficacy than others, they have revealed significant differences in side-effect profiles. The literature (such as it is) does not support the superiority of any one agent over another.124

Metaxalone has the fewest reported side effects of any SMRs and seems to be the safest. Although cyclobenzaprine may not share the dangerous cardiac and neurological potential of its close relatives the tricyclic antidepressants, it does share other properties, particularly confusion, lethargy, and anticholinergic side effects. Carisoprodol presents the most significant concern, particularly because of its potential for dependence and abuse. Several investigators have called for carisoprodol to be classified as a controlled substance.124–128 There is one older RCT supporting the use of Clonazepam.129

At the other end of the side-effect/toxicity spectrum is carisoprodol, which continues to be heavily prescribed. A questionnaire study of physicians and patients revealed that although 95% of the physicians in the study were aware of the abuse potential of meprobamate, only 39% thought that carisoprodol had abuse potential, and only 18% were aware that it is metabolized to this controlled substance (meprobamate).130 Physicians should be aware of the full range of risks and benefits of this class of medications and be alert for patients with a history of chemical abuse, particularly barbiturates or benzodiazepines, and older patients with fall potential or those prone to oversedation or confusion.131 Skeletal muscle relaxants should be used only for the short-term treatment of MPS, and their use should be carefully monitored.

Trigger point injections with either local anesthetic alone, or with steroid are traditional treatments for MPS, interestingly without much evidence on which to base that legend.2,132 This embarrassing situation is actually not uncommon with regional anesthesia treatments in general.

Botulinum toxins are being used more often for treatment of MPS 133–135; however, the evidence base for this line of therapy is rather weak with small underpowered trials. The idea that trigger points represent focal areas of ischemia and necrosis, or that botulinum toxins cause relaxation of these ischemic area with improved blood flow, or that this has an impact on pain report has not been effectively investigated. Botulinum A toxin injection was equal to methylprednisolone injection in one small randomized controlled trial.134

Research Critique

Without standard diagnostic criteria, it is unlikely that any real progress will be made in pathophysiological, mechanistic, or intervention research in MPS. Clear, unequivocal, and published entry criteria for each trial will serve to improve this situation in the short term. Validation of statistically generated ‘proposed criteria’ should be funded, and performed.19 Larger and longer trials applying the well-known principals of biomedical research are needed.

Summary

Muscle pain syndromes are extremely common and are the most likely pathoetiology of chronic pain seen in any medical context today. There are two distinct types of nonrheumatologic pain originating from muscle: the regional, posttraumatic MPS and the less common whole-body FM. Although formal analysis of empiric techniques for distinguishing between these two are lacking, a familiarity with the ACR criteria for FM and the works of Travell and Simons will allow the clinician to comfortably specify which is extant, at least in general. The research base is growing and improving in quality, yet there is considerable room for improvement. Better powered trials, more applicable outcomes, and more efficient statistical schemes are needed. The treatment schemes are partially distinct, with some significant overlap occurring if the syndromes become chronic. In that case, a thoughtful, balanced interdisciplinary approach is critical to a successful outcome. Aggressive cotreatment of psychological disorders is essential for success. FM occurs more frequently in women than in men, whereas MPS seems equally in either gender.

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