Pain in Youths With Neuromuscular Disease

Abstract

To examine the prevalence and characteristics of pain in children with neuromuscular disease (NMD), 42 youths with NMD underwent 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 (M = 14.8, SD = 2.96). Participants included 14 (37%) with Duchenne-muscular dystrophy, 6 (14%) with myotonic dystrophy, 2 (5%) with Becker dystrophy, 2 (5%) with limb-girdle dystrophy, 2 (5%) with congenital muscular dystrophy, 1 (2%) facioscapulohumeral, and 15 (36%) were classified as “other NMD.” Twenty-one (50%) were ambulatory; 26 (62%) used power wheelchairs/scooters, 9 (2%) used manual wheelchairs, 3 (.07%) used crutches/canes, and 1 (2%) used a walker. A total of 23 (55%) of the youths reported having chronic pain. Current pain intensity was 1.30(range=0–6), mean pain intensity over the past week was 2.39 (range = 0–7), mean pain duration was 8.75 hours (SD=12.84). Pain in the legs was most commonly reported and 83% reported using pain medications. This study indicates that chronic pain is a significant problem in youths with NMD. These data strongly support making comprehensive pain assessment and management an integral part of the standard of care for youths with NMD.

Introduction

Historically pain has not been considered to be a major part of the symptom manifestation of neuromuscular disease (NMD). However there are now a growing number of studies indicating that chronic pain is a common symptom for the majority of people with NMD. Studies of adult persons with a variety of NMDs, including facioscapulohumeral (FSHD), myotonic (MMD), and limb girdle LGMD) forms of muscular dystrophy, the spinal muscular atrophies (SMA), Charcot-Marie-Tooth (CMT) disease, and postpolio syndrome (PPS), have shown reported rates of chronic pain ranging from 70%, to 96%.^1–12 In general, the frequency and intensity of pain reported in adults with NMD is significantly greater than levels of pain reported by the general US population, and comparable to pain reported by adults with osteoarthritis and chronic low back pain.^1–12

Recently there has been increasing attention and resources directed towards recognizing, understanding, and managing chronic pain in children with NMD.¹³ Zebracki and Drotar recently examined the prevalence and characteristics of pain in children with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), including exploring any disagreements regarding pain symptoms among children, parents, and physicians.¹⁴ Their data showed that the majority of boys (54%–80%) with DMD/BMD (these disorders affect males only) reported experiencing pain. Parental reports of pain were higher (70%–90%). Pain typically occurred in the lower back, spine, and legs, and was described as “aching.” Both children and parents indicated significantly more intense pain than the physician. This study indicates that pain is not only common in boys with DMD/BMD but is also under recognized by treating physicians.

This is consistent with the frequency of pain reported in other disabling childhood disorders, including cerebral palsy (CP), where the experience of pain continues into the adult years as well.^15–19

The extent and nature of pain in other forms of childhood NMD has not been well studied. The purpose of this study was to explore the nature and scope of chronic pain in a sample of youths with NMD. Secondary aims included gaining specific knowledge about the nature of pain, including defining the (1) pain frequency, (2) pain intensity, (3) pain location, (4) pain quality, (5) pain interference with function and quality of life (QoL), and (6) pain interventions and their effectiveness.

Methods

Participants

All youths who met the study criteria were invited to participate in this study. The study was approved by the Institutional Review Board of Children’s Hospital and Regional Medical Center (CHRMC; Seattle, Washington) and the Muscular Dystrophy Association (MDA) prior to data collection. Youths with NMD and their parents were recruited through mailings from the rehabilitation medicine, neurodevelopmental, and spasticity clinics at CHRMC, a summer camp for youths with NMD, in addition to public postings and word of mouth. Inclusion criteria for youths included (1) primary diagnosis of NMD, (2) chronological age between 8 and 20 years, (3) capable of expressive communication using augmentative communication devices as needed, (4) use of English as the primary language, and (5) no more than mild cognitive impairment as measured on a modified Mini-Mental Status Evaluation (MMSE).²⁰

Procedures

Youths completed the questionnaires either in person or over the telephone, depending on the family preference, distance from the university, and speech intelligibility on the telephone. Parents or guardians completed their questionnaires simultaneously during in-person youth interviews or through the mail for those youths doing telephone interviews. At the beginning of the interview, the study was explained and informed parent/guardian consent and youth assent were obtained. For those youths participating by telephone, informed parent/guardian consent and youth assent were obtained prior to the interview.

Measures

A structured 1-time interview questionnaire was developed for the study and consisted of 7 sections:

1. Demographic/descriptive data were collected from parent reports and included sex, age, ethnicity, type of NMD, use of mobility devices and orthotics/splints, use of augmentative or alternative communication devices, and income.

2. Youths who reported recurrent bothersome pain of at least 3 months’ duration were then queried about pain characteristics and locations. Pain lasting

3. months or longer is considered chronic pain.^21,22 Each participant was asked specific questions about pain locations throughout the body. Pain intensity was rated specific to each pain location on an 11-point numerical rating scale (NRS) from 0 to 10 in which 0 = no pain and 10 = pain as bad as could be. Pain frequency, pain duration, and exacerbating and relieving pain factors were participant-identified. The numerical rating scale^23,24 has been shown to be reliable and valid for youths as young as 5 years of age. 3. Pain interference was assessed through use of a modified Brief Pain Inventory (BPI).^25–27 The BPI is a valid and reliable instrument designed to measure pain interference.^25–27 Degree of interference with daily activities and participation was measured for the primary pain location. The amount of pain interference in the past week was rated using an 11-point NRS where 0 = does not interfere and 10 = interferes completely. Since many persons with physical disabilities may be nonambulatory, interference with “ability to get around” replaced the original question of interference with “ability to walk.” One question was slightly modified for content to make it more age appropriate (ie, “normal work” was changed to “school or play”). To obtain more information on activities and participation, the investigators added items for interference with self-care, social activities, and recreational activities, communication with others, and learning new information or skills.

4. A parent described the child’s level of gross motor function using descriptive categories based on a modified Gross Motor Function Classification System( GMFCS).²⁸ The original GMFCS is a reliable and valid standardized rating system for children with CP to provide an objective classification of their gross motor function. The modification was the addition of the category “walks without restrictions and has no limitations in gross motor skills.”

5. Youth responded to the Functional Disability Inventory (FDI) to provide information on disruption of typical physical and social activities, including schoolwork, due to illness, pain, or disability. ²⁹ The FDI is comprised of 15 behaviors related to functioning in child-relevant settings. For example, “In the last few days, would you have had any physical trouble or difficulty doing these activities (eg, being at school all day)?” Participants were provided with a visual scale to rate their responses on a 1-to-5 scale where 1 = no trouble and 5 = impossible. The FDI has acceptable psychometric properties.^27,29

6. Youths reported on the average duration of pain over the past 4 weeks in the body location they identified as most painful. Youths were also asked to report on the frequency of pain at this or these pain locations in the past 4 weeks, using a scale of 1 to 4 where 1 = always, 2 = daily, 3 = weekly, and 4 = monthly.

7. The parent was asked to identify treatments used for his or her child’s pain, using a checklist. The list included physical therapy, transcutaneous electrical nerve stimulation (TENS), therapeutic massage, occupational therapy, counseling or psychotherapy, and medications (eg, narcotics, nonsteroidal anti-inflammatory drugs [NSAIDS], acetaminophen). The parent also had the option of writing in any additional treatments used. The parent also rated the helpfulness of treatment using a 6-point NRS where 0 = not at all and 5 = extremely, duration of the treatment use, and whether that pain intervention is currently used.

To eliminate potential influence on responding, parents and their children were queried separately about the youths’ experience of chronic pain. For the purposes of this study, the frequency of chronic pain reported by the youths themselves was used for data analysis, rather than the frequency of pain reported by the parents, as this was considered to be a more reliable indicator of actual pain experience.^30,31

Results

Fifty-three parent-and-child dyads were approached. A total of 42 completed parent-and-child (dyad) structured questionnaires met inclusion criteria. Of all the potential participant dyads approached about the study, 12 youths were classified as ineligible; 9 did not pass the modified MMSE and 3 youths were classified by their parents as ineligible (no specific reason given). One youth declined to participate. The mean duration of the interview of the youths with pain was 32 minutes (SD = 13.5 minutes). None of the participants used augmentative or alternative communication devices.

Description of Participants

Parental reports indicated the following. The sample consisted of 24 males (57%) and 18 females (43%) with ages ranging from 9 to 20 years (M = 14.8, SD = 2.96). Most of the participants (n = 36; 86%) were Caucasian, 3 (7%) were African American, (3) 7% were Asian American, 2 (5%) were Hispanic, and 1 (2%) reported “other.” The median annual household income was reported as US$40 000 to US$50 000.

Parental reports indicated 14 (37%) had DMD, 6 (14%) had MMD, 2 (5%) BMD, 2 (5%) LGMD, 2 (5%) had congenital muscular dystrophy, 1 (2%) FSHD, and 15 (36%) were classified as “other NMD,” which included the CMT syndromes, all forms of SMA, and many forms of mitochondrial and congenital myopathies. Multiple comorbid medical conditions were reported, including asthma (n = 6, 14%), headaches (n = 3, 7%), and recurrent abdominal pain (n = 3, 7%). In addition, 1 child reported insomnia and 1 reported sleep apnea. One child was reported to have Hirschsprung disease. Twelve (29%) youths were reported to have an unspecified learning disability.

Parental reports indicated 25 (60%) of the youths had at least 1 joint contracture. Contractures were reported for all joint locations. The most common contracture locations identified were the ankles (n = 17, 41 %), knees (n = 17, 41%), hips (n = 12, 29%), elbows (n = 11, 26%), spine (n = 8, 19%), wrists (n = 8, 19%), fingers (n = 5, 12%), toes (n = 4, 10%), and shoulders (n = 3, 7%). Many of the youths had orthopedic surgeries, including spinal fusion/stabilization (n = 12, 29%), tendon transfers/lengthening (n = 6, 14%), and contracture release (n = 1, 2%). Three participants (7%) had undergone gastrostomy tube replacement for nutritional support.

In terms of locomotion, 21 (50%) were full-time ambulators without assistive devices. Of the remaining youths, 13 (31%) used power wheelchairs, 4 (10%) used manual wheelchairs, 3 (7%) used crutches/canes, and 1 (2%) used a walker for mobility at home and in the community. We separated data on home and community settings. Splints/orthotics were used by 15 (36%) participants.

Thirty (71%) of the children were reported by their parents to have chronic pain, where as only 23 (55%) of the youths themselves reported having chronic pain. Pain frequency is presented in Table 1. The mean current pain intensity using the 11-point NRS was reported as 1.30 (range = 0–6). The mean pain intensity over the past week was 2.39 (range = 0–7). The reported duration of the pain episodes experienced by the youths ranged from brief episodes lasting a minute to prolonged episodes of pain lasting as long as 2 days. The mean pain duration was 8.75 hours (SD = 12.84).

Table 1.

Pain Frequency (n = 42)

	Frequency	Percentage
None of the time	10	24
Once or twice/week	12	28
A few times/week	11	26
Fairly often	4	10
Very often	2	5
Everyday or almost everyday	3	7

Data From NMD Youths Who Reported Chronic Pain

Of the youths who reported chronic pain (n = 23), most experienced pain in multiple body locations. Pain in the legs was most commonly reported. Table 2 displays the frequency and range of pain intensity per body location. Pain interfered with all 12 items on the modified BPI. The range of interference was mild to severe. Table 3 presents data on pain interference for all of the BPI items.

Table 2.

Pain Location and Numerical Rating Scale (NRS) Pain Intensity (n = 23)

Location	N (%)	Min	Max	Mean	SD
Legs	23 (100)	1	8	5.36	1.86
Back	15 (65)	1	7	3.87	1.77
Head	13 (57)	1	6	3.69	1.65
Bottom/hips	13 (57)	1	5	3.31	1.55
Feet	13 (57)	1	10	4.85	2.76
Neck	10 (44)	2	5	3.40	1.17
Shoulders	10 (44)	2	7	3.50	1.65
Arms	6 (26)	1	4	2.33	1.03
Belly/pelvis	6 (26)	1	9	4.17	3.06
Chest	7 (30)	1	10	3.43	3.04
Hands	4 (17)	2	6	3.00	2.00

Table 3.

Pain Interference With Life Domains (n = 23)

	N (%)	Min	Max	Mean	SD
Sleep	14 (61)	1	8	3.36	2.17
General activity	14 (61)	1	6	3.29	1.54
Mood	13 (57)	1	7	2.92	1.60
Mobility (ability to get around)	12 (52)	1	6	3.83	1.74
School/work	12 (52)	1	10	4.08	2.93
Recreational activities	11 (48)	1	7	3.45	1.97
Self-care (taking care of daily needs)	9 (39)	1	7	2.89	1.83
Learning new information or skills	8 (35)	1	9	3.50	2.88
Relations with other people	8 (35)	1	6	3.13	1.46
Communication with others	8 (35)	1	5	2.50	1.41
Enjoyment of life	7 (30)	1	5	3.57	1.62
Social activities	7 (30)	1	7	3.57	2.44
Communication with others	8 (35)	1	5	2.50	1.41

Youths with NMD identified a wide range of exacerbating and relieving pain factors, as detailed in Table 4. As can be seen from Table 4, there was a wide range of factors that exacerbated pain. They included “feeling down,” cold weather or being cold, eating, lifting, prolonged sitting or lying, running, standing, and touch. The most commonly reported factors that helped to relieve pain identified by the youths are presented in Table 5. Lesser common strategies that were identified to help relieve pain included changing body position/posture, swimming, sitting, warmth, changing activity, and wearing socks.

Table 4.

Factors Exacerbating Pain

Factor	N (%)
Exercise	11 (48%)
Walking	7 (30%)
Stress	6 (26%)
Stretching	8 (35%)
Wearing a splint/prosthesis	0 (0%)

Table 5.

Factors Relieving Pain

Factor	N (%)
Relaxing activities	14 (61%)
Rest/sleep	12 (52%)
Medication	11 (48%)
Stretching	10 (44%)
Exercise	7 (30%)

Table 6 details the frequency and helpfulness of pain treatment. A significant number of youths reported using both over-the-counter analgesics (eg, acetaminophen, NSAIDS) and prescription opioid medication.

Table 6.

Frequency and Helpfulness of Pain Treatment

Intervention	Ever Used, N (%)	Currently Using, N (%)	Helpfulnessa Mode (range)
Nonsteriodal anti-inflammatories	19 (83)	11(57)	3.0 (0–5)
Acetaminophen	19 (83)	11 (57)	3.0 (0–5)
Physical or occupational therapy	12 (52)	7 (58)	3.0 (0–5)
Tricyclic antidepressants	4 (17)	2 (50)	2.0 (0–5)
Opioid medications	4 (17)	2 (50)	4.5 (3–5)
Counseling/psychotherapy	2 (9)	1 (50)	4.5 (2–5)
Therapeutic massage	1 (4)	1 (50)	5
TENS	0 (0)	0 (0)	0

Abbreviation: TENS, transcutaneous electrical nerve stimulation.

^a0 = not at all, 5 = extremely helpful.

Discussion

Our study indicates that pain is a commonly experienced symptom in youths with NMD. Over 70% of the parents reported chronic pain in their children with NMD and more than half of the youths self-reported chronic pain. This finding is consistent with previous studies of adults and youths with various disabling conditions, including spinal cord injury, cerebral palsy, amputation, and neurological injuries.^{1–9,14,15–18,32–37} Previous studies in adults with NMD show that a significant percentage have substantial problems with pain, severe enough that it negatively affects both functional capacity and QoL.^1–9

Reported pain intensity ranged from 0 (no pain) to 7 (severe), with the typical pain episode lasting almost 9 hours. Although some pain episodes were of mild intensity, the duration was long. The potential effect of protracted duration of pain, even when the intensity is mild, has implications for youths’ engagement in activities and participation as well as depression, suffering, and overall QoL. Chronic pain has been previously reported as negatively affecting many aspects of youth and adolescent life.^38–41 Our data support this as more than three quarters of the youths reported that pain indeed affected their daily routines, activity, and participation. In addition, a small subsample reported severe pain intensity.

The high percentage of youths with NMD in this sample reporting chronic pain, and in multiple locations, highlights the need for clinicians working with youths with NMD to routinely inquire about the presence of chronic or recurrent pain and the pain locations throughout the entire body. Pain is often not routinely assessed by health care providers. Moreover, studies have shown that physicians frequently underestimate the severity of pain experienced by patients with disabilities, particularly in the context of disability or disruptive behavior, both of which may be present in this population.^42–45 Thus, pain management may not even be considered.

Our data also suggest that multiple methods for pain management may prove beneficial as youths reported using a variety of measures, all affording at least some temporary relief. However, in our study sample, the effects of various strategies to alleviate pain are inconsistent and appear to be individualized. For example, for some youths exercise exacerbated pain, while for others it alleviated pain. This is similar to the experience of children with CP.^15–18 Given the complexity of all forms of NMD, it is likely that the best pain management strategies would entail an individualized, multimodality approach to have the most chance of success. However, further research is indicated before any specific conclusions can be drawn.

From a clinical perspective, the loss of mobility and physical function is likely playing a major role in the experience and processing of pain in youths with NMD. Coping responses, and other psychosocial factors, have been reported to significantly impact the experience of chronic pain in the adult NMD population.² Moreover, measures of psychological functioning and pain interference are associated with multiple psychosocial variables in the adolescent patient population.^46,47 Thus, the adolescent with disability would be at high risk to develop maladaptive pain-coping strategies. Untreated chronic pain could potentially be an underlying cause of antisocial or disruptive behavior that has been reported in this patient population.^13,14,41,45 These behaviors may place enormous stress on interpersonal relationships within the family structure, which is often ill equipped to handle the stresses of caring for a child with disability.⁴⁸

Our data also suggest that sleep and mood disorders are more commonly reported in the youths with NMD who report chronic pain. Nearly 80% of the youths with NMD in our sample reported experiencing some sleep problems. The magnitude of this problem is great and has implications not only on the health and well being of the youths, but on a cascade of effects on the family of the child who experiences chronic sleep problems. Some possible causes for sleep disruption may be related to physical aspects of NMD such as inability or limited ability to adjust one’s position while sleeping or airway insufficiency secondary to hypotonia, as reported by the youth with sleep apnea in our sample. Sleep-disordered breathing is very common in the pediatric NMD population, particularly DMD and SMA.^49–58 This is due primarily to weak muscles of inspiration and expiration. ^49–58 However, there may also be a component of diminished central drive to breathe in some of the NMDs, most notably MMD and DMD.^49,51 Phrenic nerve dysfunction may also contribute to nocturnal hypoventilation in CMT.^56,58 Additionally, about one quarter of our sample of youths with NMD complained of restless/aching legs. Impaired sleep quality is known to contribute to daytime symptoms of inattention, irritability, poor impulse control, hyperactivity, or poor academic performance in able-bodied adolescents with chronic pain.^59,60 In our study, chronic pain and fatigue could be, at least partially, due to an underlying sleep disorder secondary to nocturnal hypoventilation and this may be an important target for clinical intervention.

Although the qualitative nature of our methodology and lack of a control group limit the extent to which conclusions can be firmly drawn, our data nevertheless clearly indicate that chronic pain is a significant problem for youths with NMDs. The next step would be multicentered studies done with larger numbers of children, each focusing on a single NMD, rather than a diverse mixture of diseases such as was done in this study. Separating out studies into single-disease entities would allow investigators to compare the experiences of children with differing disorders, both myopathic and neuropathic. This would hopefully permit the formulation of better, more specific diagnostic tools and ultimately facilitate the development of effective treatment paradigms. Challenges include dealing with the progressive nature of the vast majority of NMDs, which creates a “moving target” for clinicians trying to provide effective treatment. Thus, future studies would optimally be prospective and longitudinal. This would help best determine the complex interrelationships between chronic pain, physical disability, sleep and mood disorders, and family and interpersonal relationships in persons with NMDs across the lifespan. In the meantime, our current study, as well as other studies cited herein, provide ample evidence that youths and adults with NMDs do experience significant problems with pain that negatively affect almost every aspect of their lives. Clinicians caring for this patient population need to begin more effectively addressing these issues, perhaps first and foremost by simply inquiring about the nature and extent of pain in the patient with NMD, the nature and extent of their pain. Given the findings in our study, optimal treatment would likely be multimodal, involving not only pharmaceutical agents but also physical rehabilitation and psychosocial interventions.