Introduction

Neuromuscular disorders (NMDs) include a variety of conditions that affect components of a motor unit, sensory and autonomic nerves, or their supportive structures, such as myopathies, disorders of the neuromuscular junction, and neuropathies. To date, there are no curative treatments available for any NMD. Most patients with NMD understand that they will have to reconcile themselves to rehabilitation or perhaps even simply palliative treatment, and dealing with chronic pain is part of that paradigm.

One important goal of a clinician treating someone with NMD is to lessen the disease burden by treating chronic pain. This is important, given the body of evidence indicating that chronic pain is a major part of the disease burden in NMD, and in most neuromuscular diseases in general. Despite this, pain is often underdiagnosed and treatment is often overlooked. Although chronic pain is often very difficult to treat, there are at least some aspects than can potentially be ameliorated with treatment, which is unlike so many other aspects of NMD. The more difficult task might be defining how chronic pain affects burden of disease, which refers not only to the burden that ill health and risk factors place on the patient with NMD but on society as well. Measures of this burden include prevalence, mortality, life expectancy, economic costs, hospitalization rates, and specific measures of quality of life and disability.

The first investigations that defined chronic pain as a significant part of the disease burden in NMD resulted from a collaborative effort between the chronic pain research group at the University of Washington (UW), and the University of California, Davis (UCD) National Institute on Disability and Rehabilitation Research (NIDRR) Neuromuscular Research Training Center. This was done through a series of sequential program project grants initially funded by the NIDRR, the National Institutes of Health, the National Institute of Child Health and Human Development, and the National Center for Medical Rehabilitation Research. The funding for this research continues as a part of a Rehabilitation Research and Training Center on Aging with Disability at UW and the UCD Neuromuscular Research Training Center, both funded by NIDRR.

Why is pain overlooked in NMD?

With respect to evaluating patients with NMD, most of this care is still centered on diagnosis and subsequent treatment, with the aim of treatment being disease modification, rather than palliation. In terms of diagnostic workup, this is appropriate. Most of the clinical care of patients with NMD is delivered by neurologists and physiatrists. Neurologists are trained to detect specific abnormal neurologic signs, such as motor weakness, lack of fine motor coordination, or a Babinski sign, and then use those findings to direct a workup that will arrive at the correct disease diagnosis. On the other hand, physiatrists are specifically trained to try, with as much structure as possible, to evaluate impairment and identify disability, such as not being able to climb the stairs, which then results in an inability to use public transport. It is the job of the physiatrist to identify disability and promote interventions to minimize it, including facilitating access to appropriate assistive devices, such as wheelchairs, hearing aids, orthoses, prostheses, and so forth. Indeed, any clinician, including neurologists, other physicians, and therapists can do this but may not be specifically trained or oriented toward providing this service. Ultimately, the overarching goal is to ease disease burden and help ensure the inclusion and participation of people with disabilities into mainstream society; however, evaluation and modification of disease burden is currently not included as part of any clinical algorithm.

Further, pain is a phenomenological experience rather than an objective sign. The International Association for the Study of Pain uses this definition: “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” ( http://www.iasp-pain.org ). As such, many clinicians used to assessing symptoms via objective signs struggle with the idea of a symptom that is best assessed by asking, then listening to and relying on the report of the patient. Moreover, pain is influenced by a large number of biologic, psychological, and social contextual factors. Thus, chronic pain is best assessed and treated at a multidisciplinary pain treatment center. However, chronic pain needs to be identified as part of the patient’s diagnoses before that referral would be undertaken.

The other barrier in the current health care algorithm is funding. Although there is some activism by organizations, such as the Muscular Dystrophy Association (MDA) to support the integration of rehabilitation services into the public health system, owing to economic issues, many Medicaid-sponsored and Medicare-sponsored health programs have little or no covered rehabilitation services. It will take ongoing collaborative efforts on the part of NMD physician specialists and other clinicians in both academia and the private sector, as well as nongovernmental organizations like the MDA, to keep pressure on federal and state governments to include comprehensive services for disabled people as a routine part of health care coverage. As it is now, the vast majority of patients with NMD are unemployed and, as such, are on state funding (Medicaid) with federal backup coverage (Medicare). Fowler and colleagues identified factors that limited employment opportunities for individuals with slowly progressive NMD. At the time of their study in the late 1980s, only 40% of subjects with NMD were employed in the competitive labor market, with 50% having been employed in the past, and 10% having never been employed. Strikingly, the major consumer barrier to employment was education. Physical impairment and disability were not associated with level of unemployment. Rather, psychological characteristics were associated with level of unemployment, including intellectual capacity, psychosocial adjustment, and the belief by most individuals that their physical disability was the only or major barrier to obtaining a job. The problem was compounded by a low level of referrals to the Department of Vocational Rehabilitation (DVR) by physicians, and ultimately a low acceptance rate into the DVR programs. The irony here is that a population of disabled patients with extensive medical problems ends up being unemployed, and thereby on the most restrictive form of health care coverage. This, in turns, leads to limited resources to evaluate and treat complex problems, such as chronic pain, in the disabled population.

There is also a need for better ways to assess chronic pain and determine its impact on functional status in patients with NMD. As mentioned previously, although function may be objectively measured with performance-based scales, such as the functional independence measure (FIM), Barthel index, and timed motor performance measures, among many others, pain is a personal experience that requires patient self-report for valid assessment.

Patient self-report measures have been shown to be reliable and valid in the NMD population, and these scales retain that validity when tested in an NMD population with chronic pain. For example, the internal consistency coefficients of the self-reported FIM (FIM-SR) scale ranges from adequate to excellent (Cronbach alpha range, 0.73–0.98; median, 0.96). FIM-SR scales associated with motor function discriminate between those subjects who report being ambulatory and those who report requiring use of a wheelchair or other assistive device for mobility. Finally, FIM-SR scales discriminate between different types of NMDs, with patients with amyotrophic lateral sclerosis (ALS) showing significantly lower scores on the FIM-SR self-care, motor, and total scores than all other NMD diagnostic groups, and showing significantly lower scores on the FIM-SR sphincter control, mobility, and locomotion scales than most of the other diagnostic groups. Thus, the FIM-SR scales appear to be reliable and valid measures of independence in 6 specific (self-care, sphincter control, mobility, locomotion, communication, social cognition) and 3 global (motor, cognition, total) areas of functioning in persons with NMD and chronic pain. Although no one wishes to diminish the personal suffering of anyone suffering from ill health, these measures can be used to compare levels of public health spending or levels of research funding and scientific interest. These comparisons can be useful and identify any large inequalities in funding that could lead to an increased societal burden of disease.

Why is pain overlooked in NMD?

With respect to evaluating patients with NMD, most of this care is still centered on diagnosis and subsequent treatment, with the aim of treatment being disease modification, rather than palliation. In terms of diagnostic workup, this is appropriate. Most of the clinical care of patients with NMD is delivered by neurologists and physiatrists. Neurologists are trained to detect specific abnormal neurologic signs, such as motor weakness, lack of fine motor coordination, or a Babinski sign, and then use those findings to direct a workup that will arrive at the correct disease diagnosis. On the other hand, physiatrists are specifically trained to try, with as much structure as possible, to evaluate impairment and identify disability, such as not being able to climb the stairs, which then results in an inability to use public transport. It is the job of the physiatrist to identify disability and promote interventions to minimize it, including facilitating access to appropriate assistive devices, such as wheelchairs, hearing aids, orthoses, prostheses, and so forth. Indeed, any clinician, including neurologists, other physicians, and therapists can do this but may not be specifically trained or oriented toward providing this service. Ultimately, the overarching goal is to ease disease burden and help ensure the inclusion and participation of people with disabilities into mainstream society; however, evaluation and modification of disease burden is currently not included as part of any clinical algorithm.

Further, pain is a phenomenological experience rather than an objective sign. The International Association for the Study of Pain uses this definition: “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” ( http://www.iasp-pain.org ). As such, many clinicians used to assessing symptoms via objective signs struggle with the idea of a symptom that is best assessed by asking, then listening to and relying on the report of the patient. Moreover, pain is influenced by a large number of biologic, psychological, and social contextual factors. Thus, chronic pain is best assessed and treated at a multidisciplinary pain treatment center. However, chronic pain needs to be identified as part of the patient’s diagnoses before that referral would be undertaken.

The other barrier in the current health care algorithm is funding. Although there is some activism by organizations, such as the Muscular Dystrophy Association (MDA) to support the integration of rehabilitation services into the public health system, owing to economic issues, many Medicaid-sponsored and Medicare-sponsored health programs have little or no covered rehabilitation services. It will take ongoing collaborative efforts on the part of NMD physician specialists and other clinicians in both academia and the private sector, as well as nongovernmental organizations like the MDA, to keep pressure on federal and state governments to include comprehensive services for disabled people as a routine part of health care coverage. As it is now, the vast majority of patients with NMD are unemployed and, as such, are on state funding (Medicaid) with federal backup coverage (Medicare). Fowler and colleagues identified factors that limited employment opportunities for individuals with slowly progressive NMD. At the time of their study in the late 1980s, only 40% of subjects with NMD were employed in the competitive labor market, with 50% having been employed in the past, and 10% having never been employed. Strikingly, the major consumer barrier to employment was education. Physical impairment and disability were not associated with level of unemployment. Rather, psychological characteristics were associated with level of unemployment, including intellectual capacity, psychosocial adjustment, and the belief by most individuals that their physical disability was the only or major barrier to obtaining a job. The problem was compounded by a low level of referrals to the Department of Vocational Rehabilitation (DVR) by physicians, and ultimately a low acceptance rate into the DVR programs. The irony here is that a population of disabled patients with extensive medical problems ends up being unemployed, and thereby on the most restrictive form of health care coverage. This, in turns, leads to limited resources to evaluate and treat complex problems, such as chronic pain, in the disabled population.

There is also a need for better ways to assess chronic pain and determine its impact on functional status in patients with NMD. As mentioned previously, although function may be objectively measured with performance-based scales, such as the functional independence measure (FIM), Barthel index, and timed motor performance measures, among many others, pain is a personal experience that requires patient self-report for valid assessment.

Patient self-report measures have been shown to be reliable and valid in the NMD population, and these scales retain that validity when tested in an NMD population with chronic pain. For example, the internal consistency coefficients of the self-reported FIM (FIM-SR) scale ranges from adequate to excellent (Cronbach alpha range, 0.73–0.98; median, 0.96). FIM-SR scales associated with motor function discriminate between those subjects who report being ambulatory and those who report requiring use of a wheelchair or other assistive device for mobility. Finally, FIM-SR scales discriminate between different types of NMDs, with patients with amyotrophic lateral sclerosis (ALS) showing significantly lower scores on the FIM-SR self-care, motor, and total scores than all other NMD diagnostic groups, and showing significantly lower scores on the FIM-SR sphincter control, mobility, and locomotion scales than most of the other diagnostic groups. Thus, the FIM-SR scales appear to be reliable and valid measures of independence in 6 specific (self-care, sphincter control, mobility, locomotion, communication, social cognition) and 3 global (motor, cognition, total) areas of functioning in persons with NMD and chronic pain. Although no one wishes to diminish the personal suffering of anyone suffering from ill health, these measures can be used to compare levels of public health spending or levels of research funding and scientific interest. These comparisons can be useful and identify any large inequalities in funding that could lead to an increased societal burden of disease.

What do we know about pain in NMD now? a brief review of the literature

Recently, Jensen and colleagues systematically reviewed the research findings regarding the associations between psychosocial factors and adjustment to chronic pain in persons with physical disabilities. They performed a comprehensive literature search on a number of major diagnostic groups, including muscular dystrophy, in addition to spinal cord injury, acquired amputation, cerebral palsy, and multiple sclerosis. Perhaps not surprisingly, psychosocial factors were shown to be significantly associated with pain and dysfunction in all disability groups, including muscular dystrophy. The psychosocial factors most closely associated with pain and dysfunction across the samples included (1) catastrophizing cognitions; (2) task persistence, guarding, and resting coping responses; and (3) perceived social support and solicitous responding social factors. Thus, psychosocial factors are clearly important predictors of pain and functioning in persons with physical disabilities, including muscular dystrophy, a subset of NMD.

The importance of psychosocial factors in chronic pain for patients with NMD has been confirmed in other studies as well. Nieto and colleagues studied a sample of 107 adults with either myotonic muscular dystrophy (MMD) or facioscapulohumeral muscular dystrophy (FSHD). A sample of 107 adults with either MMD or FSHD reported pain in the past 3 months, completing assessments at 2 time points, separated by approximately 24 months. The results showed that changes in pain-related psychological variables were significantly associated with changes in psychological functioning, pain intensity, and pain interference. Specifically, increases in the belief that emotion influences pain and catastrophizing were associated with decreases in psychological functioning. Increases in the coping strategies of asking for assistance and resting, and the increases of catastrophizing were associated with increases in pain intensity. Finally, increases in pain intensity and asking for assistance were associated with increases in pain interference. These results further support the use of the biopsychosocial model of pain for understanding pain and its impact in individuals with MMD or FSHD.

Miró and colleagues studied 182 persons with either FSHD or MMD in a similar fashion. They found that greater catastrophizing was associated with increased pain interference and poorer psychological functioning, pain attitudes were significantly related to both pain interference and psychological functioning, and coping responses were significantly related only to pain interference. In addition, greater perceived social support was associated with better psychological functioning. The results support the use of studying pain in persons with MMD/FSHD from a biopsychosocial perspective, and the importance of identifying psychosocial factors that may play a role in the adjustment to and response to pain secondary to MMD/FSHD.

Jensen and colleagues used a cross-sectional, community-based survey on a convenience sample to determine the nature and scope of pain in working-aged adults with either MMD or FSHD. Results showed that more subjects with FSHD (82%) than with MMD (64%) reported pain. The most frequently reported pain sites for both diagnostic groups were lower back (66% MMD, 74% FSHD) and legs (60% MMD, 72% FSHD). Significant differences in pain intensity were found between the diagnostic groups in the hands, legs, knees, ankles, and feet, with patients with MMD reporting greater pain intensity at these sites than patients with FSHD. Age was related to the onset of pain (participants reporting pain were younger than those not reporting pain in the FSHD sample), but pain severity was not significantly associated with age in those reporting pain. Respondents with both diagnoses, who reported mobility limitations and used assistive devices (eg, wheelchair, cane), reported more pain severity than those with mobility limitations who did not use assistive devices, who, in turn, reported more pain severity than respondents who reported no mobility limitations at all. The treatments that were reported to provide the greatest pain relief were not necessarily those that were the most frequently tried or still used. The findings indicate that pain is a more common problem in persons with FSHD than in persons with MMD, although it is common in both populations. In addition, these pain problems are chronic, underscoring the need to identify and provide effective pain treatments for patients with these NMDs.

One of the few European studies assessing pain frequency, severity, location, treatment, and relief in adults with NMD was done by Tiffreau and colleagues. Using a mailed in, self-completed questionnaire, 125 adults with a confirmed diagnosis of hereditary NMD participated (response rate = 45%). Outcome measures included self-reported motor function, anxiety and depression scores, pain intensity (on a 0–10 numeric scale) and location, frequency of pain-aggravating situations, and pain treatment and relief. Most (73%) respondents reported pain and 62% reported chronic pain (defined as pain for at least 3 months). Mean pain intensity was 6.1 of 10.0 with 40% reporting severe pain (a score of ≥7). Almost half (46%) reported anxiety, although only 16% of subjects reported depression. The most common pain-aggravating situations were “walking,” “standing,” and “muscle stretching.” Walking was more frequently cited as a pain-aggravating situation by the chronic pain population than by the acute pain population. Analgesics were used by 70% of these patients, with massage being the most frequently prescribed physical treatment (45%). Interestingly, these patients did not report adequate relief from analgesics or massage.

Guy-Coichard and colleagues published one of the largest studies to date, having mailed out 862 questionnaires to outpatients with NMD at 10 centers. A total of 511 subjects responded with answers suitable for analysis (300 men and 211 women; response rate: 59.3%). The questionnaire packet included numeric scales for pain intensity and relief, the Brief Pain Inventory, the Saint Antoine Pain Questionnaire, and a scale to assess disability. More than two-thirds of the 331 patients (67.3%) suffered pain during the last 3 months, with mean pain intensity being 4.8 ± 2.5. Pain was usually diffuse (153 patients, 44%) and intermittent (228, 71%). Pain intensity varied by the NMD diagnosis, with the most severe pain reported from patients with metabolic myopathy and myasthenia gravis.

Engel and colleagues examined the prevalence and characteristics of pain in children with NMD. A total of 42 youths completed a comprehensive evaluation, including a detailed intake interview and structured questionnaire that included demographic and functional data. Youths who reported chronic pain were further queried about pain characteristics, locations, and intensity using an 11-point numerical rating scale and a modified Brief Pain Inventory (BPI). The sample consisted of 24 males (57%) and 18 females (43%), ages ranging from 9 to 20 years (mean = 14.8, SD = 2.96). Participants included 14 (37%) with Duchenne muscular dystrophy, 6 (14%) with MMD, 2 (5%) with Becker dystrophy, 2 (5%) with limb-girdle dystrophy, 2 (5%) with congenital muscular dystrophy, 1 (2%) FSHD, and 15 (36%) were classified as “other NMD.” Twenty-one (50%) were ambulatory, whereas 26 (62%) used power wheelchairs/scooters and 9 (2%) used manual wheelchairs. A total of 23 (55%) of the youths reported having chronic pain, with pain intensity “over the past week” being 2.39 (range = 0–7). Pain in the legs was most commonly reported, and remarkably 83% reported using pain medications. This study indicates that chronic pain is also a significant problem in youths with NMD.