Pain and MS
- Pain is a common occurrence in MS, with 30-50% of patients
experiencing pain at some time in the course of their illness. Pain
typically is not associated with a less favorable prognosis, nor does it
necessarily impair function; however, since it can have significant impact
on quality of life (QOL), it needs to be treated appropriately. Pain in MS
can be classified as primary or secondary.
- Primary pain is related to the demyelinating process
itself. This neuropathic pain is characterized often as having a burning,
gnawing, or shooting quality. Nonpharmacologic techniques, such as use of
imagery or distraction, can be helpful. Transcutaneous electrical nerve
stimulation (TENS) is useful in some patients. Pharmacologic approaches
include prescription of tricyclic antidepressants as first-line drugs.
Anticonvulsants, such as carbamazepine, phenytoin, or gabapentin, can be
added as second-line agents.
- Secondary pain in MS is primarily musculoskeletal in
nature, possibly due to poor posture, poor balance, or abnormal use of
muscles or joints as a result of spasticity. Nonpharmacologic treatment for
secondary pain includes moist moderate heat, massage, physical therapy, and
exercise (eg, stretching). Pharmacologic agents include nonsteroidal
anti-inflammatory drugs (NSAIDs) or other analgesics. Use of narcotics
seldom is indicated.
Pain in multiple sclerosis: A biopsychosocial
Journal of Rehabilitation Research and Development
Vol. 39 No. 2, March/April 2002
Robert D. Kerns, PhD; Marilyn Kassirer, MD; John Otis, PhD
VA Connecticut Healthcare System and Yale University, 950 Campbell Avenue,
West Haven, CT 06516; Boston University School of Medicine and VA Boston
Healthcare System, Boston, CT 06516
Clinically significant pain has been found in as many as
65% of persons diagnosed with multiple sclerosis (MS). Acute pain conditions
include trigeminal neuralgia, painful optic neuritis, and Lhermittes
syndrome. Chronic pain conditions such as dysesthesias in the limbs, joint
pain, and other musculoskeletal or mechanical pain problems develop as a
function of spasticity and deconditioning associated with MS. These painful
conditions may respond to pharmacological, surgical, rehabilitation, and
psychological interventions. However, unresolved pain, associated disability,
and affective distress are common. In addition, efforts to manage MS and its
associated symptoms, for example, may inadvertently cause osteoporosis and
headache or other symptoms that may exacerbate pain and pain-related
disability. Conversely, efforts to manage pain may have negative effects on
the symptoms of MS (e.g., increased fatigue). A multidimensional approach to
assessment and management that is guided by a comprehensive biopsychosocial
model is recommended. Such an approach needs to consider the exacerbating
nature of MS, MS-related pain, and interventions aimed at their management.
Suggestions for future research on MS-related pain conclude the
Persons with multiple sclerosis (MS) experience a broad
array of both acute and chronic pain conditions (1-3). Published reports in
the last decade suggest that the prevalence of painful conditions among
persons with MS may range as high as 65 percent (4). A significant minority of
individuals with MS identifies pain as their most severe symptom (5). Although
pain can be managed with a combination of pharmacological and other
interventions, the largest proportion of persons reporting MS-related pain
suffer from persistent and uncontrollable pain (5). MS-related pain may be
directly related to the disease itself and characterized as central pain
(e.g., pain associated with optic neuritis and neuralgia), or it may develop
secondary to the protracted symptoms of MS (e.g., pain caused by painful
muscle contractures and stiffened joints). Unfortunately, pharmacological
treatments for MS, such as steroids and fl interferons, may also contribute to
the development of pain. Furthermore, efforts to manage pain may inadvertently
complicate efforts to manage other symptoms of MS.
In contrast to the large and growing literature on the
psychosocial aspects of acute and chronic pain conditions, more generally,
little empirical research has focused specifically on the effects of
MS-related pain on patient functioning and emotional well-being (6). Recent
research has documented that MS patients with pain reported poorer mental
health and greater deficits in social-role functioning relative to a
comparison group of individuals with MS who reported no pain (7). Other
studies suggest that as many as 50 percent of individuals with MS-related pain
may have clinical depression (8).
Kerns has proposed that a comprehensive and
multidimensional model of chronic pain may be an appropriate perspective for
informing the clinical assessment and management of MS-related pain and for
guiding future research in this area (6). This model acknowledges the need for
careful and thorough investigation of biomedical contributors to nociception
and efforts to manage pain itself. The model also argues for simultaneous
attention to pain-related disability and affective distress and to
psychosocial contributors to the development of persistent pain. In addition,
the model encourages the development of a comprehensive, multidimensional, and
often, multidisciplinary treatment plan that targets each of these dimensions
of the "chronic pain experience" (9).
In this article, we will briefly review the literature
documenting the prevalence of pain among persons with MS, the array of
specific painful conditions often identified, and strategies that are commonly
employed to manage MS-related pain. This will be followed by a consideration
of the impact of MS-related pain on psychosocial functioning. Then we will
outline a biopsychosocial model of persistent MS-related pain. The model will
be used to highlight the complexity of efforts to effectively manage symptoms
of MS, including pain, associated disability, and affective distress. A
pattern of negative interactions will be highlighted for MS patients in
relation to their pain, their caregivers' efforts to manage their pain, and
their other symptoms. We will conclude the article with suggestions for future
research informed by the model.
PREVALENCE OF MS-RELATED PAIN
Estimates of the prevalence of pain in MS range from 13
to 80 percent (10). Five relatively recent studies place the estimates at over
50 percent of MS patients. Warnell found that 233 of 364 patients reported
pain at some time since the diagnosis of MS, and 40 percent reported that they
had chronic, persistent pain (11). Stenager and colleagues assessed 117 MS
patients and reported similar findings (5). Sixty-five percent of the
participants acknowledged persistent pain (i.e., headache and "minor" acute
pain conditions were excluded) at some point since their diagnosis, and 45
percent reported pain at the time of the study. More recently, Archibald and
his colleagues sampled 85 consecutively referred outpatients at an MS research
unit and reported a pain prevalence rate of 53 percent, including head pain
(7). Nearly 18 percent of this sample reported continuous pain. Indaco and
colleagues sampled 141 patients in an outpatient neurology clinic (12).
Fifty-seven percent of their sample reported pain at some time during their
disease, while 21 percent reported pain at the onset of their disease (13).
Collectively, these and other studies document a particularly high prevalence
of pain among persons diagnosed with MS and encourage clinical efforts to
routinely assess and aggressively manage pain in this population.
These same studies provide some information about the
prevalence of specific pain conditions and the distribution of pain problems
across disease subtypes. Moulin and colleagues reported that dysesthetic leg
pain was the most commonly reported problem, followed by chronic back pain and
recurrent painful spasms of the legs (13). Stenager and colleagues attempted
to classify painful conditions by diagnosis and presumed cause (5). These
investigators reported that the most common among acute pain conditions were
neuralgia, Lhermitte's sign, pain associated with optic neuritis, and brief
painful tonic spasms. The most frequent chronic pain syndromes were reported
to be pain associated with tonic spasms, tension, and painful sensations in
the limbs, dysesthesias, and low back pain (5). Indaco and colleagues reported
a quite similar distribution of pain as these two previous reports (12). As an
alternative approach, Archibald and colleagues categorized pain by four broad
body locations (7). Of those reporting pain in at least one site, 53 percent
reported head pain, 58 percent reported arm pain, 73 percent reported leg
pain, and 49 percent reported pain in the trunk region. Pain was commonly
reported to occur in more than one site (76 percent). In addition to these
observations, Kassirer has noted that many MS therapies may exacerbate a
person's pain (4). She notes that longterm steroid treatment may cause
osteoporosis, which can lead to vertebral fractures, and J3 interferons may
cause or exacerbate migraines.
Thus far, no evidence has shown that pain occurs more
frequently in any disease subtype, namely relapsing-remitting,
relapsing-progressive, chronic-progressive, or benign (7). Only one study
could be found that included a comparison group for examination of the extent
of pain among individuals with MS. In this study, 35 persons with MS were
compared to a matched group of persons with chronic low back pain. The results
indicated that the group with MS reported significantly less pain than the
comparison group (14). To date, there is no compelling evidence that the
prevalence of pain or type of pain is reliably associated with
disease-specific variables, such as the time since onset of MS (i.e., its
duration) or indices of severity of MS, or is there consistent evidence of an
association between pain prevalence and demographic variables, such as age and
gender (5,7,12,13). The one exception appears to be pain associated with
neuropathy, which often increases in severity with disease progression (15).
Interestingly, little information is available about the
intensity of pain experienced among persons reporting MS-related pain.
Vermotte and colleagues reported that pain associated with spasms and
neuralgia was the most severe (16). Thirty-two percent of the participants in
the Stenager et al. study reported that pain was one of the worst symptoms of
MS (5). In only one study reviewed was there an effort to quantify pain
intensity with the use of a standardized measure (7). The investigators
reported average ratings of pain of 5.8 on a 0 (no pain) to 10 (highest level
of pain experienced) numeric rating scale and worst pain severity ratings of
7.7 on the same scale. In this study, pain severity was unrelated to MS
duration or symptom severity, number of pain sites, age, or gender.
In conclusion, data convincingly demonstrate a high
prevalence of pain among individuals with MS. Much of the pain experienced
becomes chronic, although characteristic acute pain conditions are also noted.
Multiple pain conditions have been identified as occurring with considerable
frequency, and most persons with pain report more than one site of pain. Are
there differences in prevalence or type of pain across disease subtypes?
remains an important question, and associations with important demographic and
disease variables remain unclear. Available data on the severity of pain,
although limited, raise concern that pain experienced by these persons is
largely uncontrolled and undertreated.
Numerous limitations of the studies reviewed can be
cited. These include relatively limited sample sizes and potential sampling
biases (e.g., reliance on convenience samples from clinical settings
specializing in the treatment of MS). Idiosyncratic methods for assessment of
site and diagnosis of pain are common, and most studies failed to employ
psychometrically sound measures routinely used in the pain field. There is a
strong need for a large-scale epidemiologic investigation that can help
address questions about the prevalence of pain conditions among persons with
MS, the distribution of pain conditions across disease subtypes, and
relationships of specific pain conditions to important demographic variables
(e.g., age, gender, and race).
MANAGEMENT OF MS-RELATED PAIN
A few reports of medication trials and reviews of common
approaches to the pharmacologic management of MS-related pain are available
(4,17). Only one published study was identified that reported data on the use
of pain medications in this population. Archibald et al. noted that only 29 of
45 participants who reported pain also acknowledged the use of medications for
pain, including over-the-counter medications, during the month before study
participation (7). Use of analgesics, primarily acetaminophen, was reported by
83 percent of the participants using pain medications, and medications usually
used to treat neuropathic pain (i.e., baclofen, carbamazepine, amitriptyline,
and phenytoin) were used by 65 percent of the sample. These data are largely
consistent with suggestions that MS-related pain may be managed with a
conservative medical treatment (17). On the other hand, the low frequency of
reported use of narcotic analgesics in this population suggests that narcotics
are not effective for central pain. It may also be important to note that over
one-third of the individuals evaluated failed to report the use of any
medication for pain. One could speculate that several reasons exist why
individuals with MS would not report the use of pain medications, including a
patient's inability to access pain medications because of being bedridden and
the patient's lack of knowledge or interest among practitioners.
Under-management of pain conditions has been recently noted to be widespread,
and it may be useful to examine more closely whether this is the case among
individuals with MS (18,19).
Pharmacological management of pain in MS has its
challenges (4). Even aggressive efforts to manage pain in MS commonly fail.
For example, carbamazine may be effective in the early stages of neuralgia,
but it may lose its effectiveness over time and alternative medications may
need to be added. In some pain conditions with MS, surgical intervention may
be indicated when medications fail. Management of painful spasticity may also
present a dilemma, since many persons with MS benefit from some use of
spasticity to facilitate standing transfers. Use of newer short-acting
medications may be useful in reducing nocturnal spasms, cramps, and spasticity
without compromising functioning during the daytime. Strategies for the
successful management of optic neuritis continue to be debated in the
literature, although the use of an intrathecal baclofen pump appears
promising. Management of chronic pain is particularly complicated, and there
are no clear guidelines for its pharmacological treatment. Ultimately, ongoing
pain is evidently quite common among persons with MS despite growing evidence
supporting the effectiveness of several classes of medications.
Rehabilitation approaches may also be helpful in the
management of MS-related pain. Soft-collars might help diminish symptoms of
Lhermitte's syndrome (17). Physical and occupational therapies that emphasize
body mechanics and reconditioning are frequently offered, but little empirical
work has been done to confirm the efficacy of these approaches for reducing
pain. Kassirer suggests anecdotally that transcutaneous electrical nerve
stimulation (TENS) may have some benefit (4).
Despite evidence of the efficacy of psychological
interventions, particularly cognitive-behavior therapy, for other chronic pain
conditions (20), limited effort has occurred to examine the efficacy of these
approaches for pain in MS. One published case study examined the effects of
hypnosis on pain in an individual with MS (21). The author reported that
sustained use of self-hypnosis contributed to pain relief in the short term,
but the examination of longer-term benefits was confounded with the
progression of the disease and other rehabilitation efforts. Dane suggested
that hypnosis might prove more beneficial if offered along with
cognitive-behavior therapy (21). No controlled studies have been done of
psychological interventions for pain in MS.
PSYCHOSOCIAL IMPACT OF PAIN IN MS
A relatively large literature has emerged that examines
the psychosocial impact of MS. Individuals with MS have been found to retire
from employment early, are more likely to experience clinical depression, are
at increased risk for suicide, experience low self-esteem, have lowered
perceptions of social support, and have lowered levels of marital satisfaction
(22,23). Importantly, however, existing data also suggest that as many as
two-thirds of persons with MS show a positive psychosocial adjustment to MS
(24). Several studies have investigated factors that predict poor psychosocial
The specific and incremental effects of pain on
psychosocial functioning and emotional well-being are only recently becoming a
focus of investigation. In perhaps the best-designed study thus far published
in this area, Archibald and colleagues (7) used well-recognized and
standardized measures of MS-related disability (Expanded Disability Status
Questionnaire) (27) and mental health status (Mental Health Inventory) (28) to
examine the impact of pain on these dimensions of psychosocial functioning.
Fifty-seven percent of those persons reporting pain indicated that their
ability to work had been reduced by 50 percent or more because of pain. Those
with pain reported significantly poorer role functioning across each of the
domains of sports person, spouse or partner, and friend, as well. Compared to
persons without pain, those acknowledging pain reported significantly poorer
overall mental functioning. Mean scores on the Mental Health Inventory for
those reporting pain fell in the lowest quartile of scores for a normative
Sullivan and his colleagues have published the only
controlled study of adjustment to MS that included an examination of the role
of pain (14). Groups of 35 persons with either MS or chronic low back pain (CLBP),
matched for age, gender, education, and employment status, responded to
several standardized questionnaires assessing adjustment to illness and
healthcare system use. Regression analyses revealed that illness duration and
behavioral coping were significant predictors of healthcare system use for
both groups of participants. Illness duration was significantly inversely
related to frequency of visits to healthcare professionals. Active behavioral
coping, that is, the propensity to plan and initiate action toward problem
resolution, was positively related to seeking care. Correlation analyses
revealed that higher pain severity was also positively related to extent of
healthcare use. Higher pain severity and avoidant coping were, as predicted,
significantly associated with greater depressive symptom severity. Comparisons
between the two groups revealed that patients with MS, relative to those with
CLBP, reported significantly more mobility problems, less pain, fewer
additional medical problems, fewer depressive symptoms, and fewer visits to
healthcare professionals. Additional analyses revealed that pain severity
accounted for these group differences in healthcare use and depressive symptom
severity. Persons with MS acknowledged greater use of cognitive coping, that
is, processes related to acceptance, than persons with CLBP. Taken together,
these results suggest that, for individuals with MS, the presence and
intensity of pain are significant contributors to overall adjustment.
Other researchers in this area have not demonstrated a
significant relationship between pain and either disability (12,13) or
depressive symptom severity (5,12). The investigation of the role of pain as a
contributor to other aspects of psychosocial functioning, such as relationship
satisfaction, anxiety, or self-esteem, has not been undertaken.
Although it is likely that pain significantly influences
physical and psychosocial functioning, limitations in this area of research
preclude substantive conclusions at this time. Clearly, further research in
this area will be important. Studies designed to tease apart the unique
contributions of pain (and interactions of pain with other symptoms of the
disease, in the prediction of social-role functioning, emotional well-being,
and overall psychosocial adjustment) will be important in informing the
development of more effective, comprehensive treatment approaches to MS.
An important area of investigation in the field of pain
medicine is the role of psychological and social factors as predictors of pain
(29). Although the biomedical contributions to the experience of specific pain
conditions in MS are increasingly clear, strong evidence from other areas
suggests that the psychosocial context of the experience of pain may play
important roles in determining the perpetuation of pain, perceived pain
intensity, pain's effects on functioning and emotional well-being, and
response to treatment (30). Variables such as distraction, coping style,
pain-related fear, anger, and spousal and family members' responses to pain
and chronic suffering in general may be particularly fruitful avenues for
investigation (31-35). In addition, the extent to which these variables relate
to mental status changes, state of disability, magnetic resonance imaging (MRI)
findings, use of medications for MS, and stage of MS should be investigated.
BIOPSYCHOSOCIAL MODEL OF CHRONIC PAIN IN MS
A multidimensional model for understanding the
experience of persistent pain may be an appropriate perspective for
considering MS-related pain. Such models have proven particularly useful in
understanding pain in other chronic painful conditions, and Kerns (6) has
recently proposed an adaptation of this perspective for pain in MS. This model
is schematically presented in the Figure.
. Diathesis stress
model of chronic pain (6). Reprinted, by permission, from IASP Press, Handbook
of Health and Rehabilitative Psychology, 331.
According to this model, chronic pain is conceptualized
as a multidimensional phenomenon that emphasizes the experience of pain, per
se, as well as associated disability and affective distress as equally
important dimensions of the "experience of chronic pain" (9). The model is
informed by diathesis-stress theory and hypothesizes that numerous
vulnerability factors interact with the stress or challenges of the experience
of pain (and MS, more generally) to influence adaptation to pain and other
symptoms of the disease. In addition to the neurobiological basis of pain,
these influences include cognitive, behavioral, and social factors such as
those outlined in the previous section. The model also explicitly acknowledges
the progressive nature of MS and emphasizes the developmental and dynamic
nature of adaptation and adjustment. Finally, the model acknowledges the
importance of the social context in which the interactions between
vulnerabilities and the stress of MS and pain occur, and recognizes the
central role of social interactions and social learning in the process of
A few examples can help to clarify the model and its
relevance for understanding pain in MS and pain-related disability and
distress. Muscle weakness, fatigue and, in particular, spasm and spasticity
are cardinal features of MS and, as already noted, can be associated with
pain. Perhaps an obvious example of the interaction between premorbid
functioning and the challenges of MS and pain is the observation that a person
with MS who relies on his or her physical integrity for employment and/or
important aspects of social-role functioning may experience disability and
distress in earlier stages of the disease than another person who has a more
sedentary lifestyle and job. This remains a potentially important area for
investigation. More subtle examples are equally compelling. Individuals vary
in their level of problem-solving competence and confidence. Those who
generally avoid problems or who lack skills to cope with some of the everyday
challenges of pain and other symptoms of MS may find it difficult to maintain
social-role functioning. These individuals may withdraw and avoid activity
that may be acutely painful and may, over the longer term, experience more
rapid deconditioning, leading to heightened pain and even greater functional
limitations. One final example relates to the development of depression, a
commonly observed sequela to MS (8,23-26). Persons vulnerable to depression,
either neurobiologically or as a function of poor social skills or pervasive
negative thinking, may be more likely to develop a clinical depression given
the challenges of MS and pain.
The model can also be useful in considering negative
interactions that may occur when one symptom or problem associated with MS, or
efforts to manage the symptom, inadvertently creates an additional
vulnerability for the development or exacerbation of pain. For example, muscle
weakness and fatigue associated with MS commonly contribute to more
generalized deconditioning and an increased likelihood of the development of
joint and muscle pain and peripheral edema. Pain and the fear of making pain
worse from activity may contribute to behavioral avoidance and to additional
decrements in productive and pleasurable activity. This may subsequently
contribute to additional fatigue and muscle deconditioning. In another
example, extended use of a wheelchair may place the MS patient at increased
risk for low back pain and skin breakdown. A common problem is associated with
the long-term use of steroids, which may contribute to the development of
osteoporosis and associated pain (e.g., vertebral fractures) as well as the
need for increased bedtime. This may increase the risk for bedsores and
additional pain in the already incapacitated patient. Pharmacological
management of spasticity and spasms may paradoxically contribute to decreased
functional independence (i.e., when a patient loses spasticity after being
medicated and falls fracturing vertebrae). It also affects the overall
capacity to participate in activities, resulting in further decrements in
self-esteem, feelings of competence, and loss of pleasure. These psychological
difficulties may be hypothesized to exacerbate existing pain and pain-related
disability and distress.
Pain is a frequent complaint among persons with MS, and
it is clear that optimal treatment or management of MS requires attention to
this problem. The high prevalence of pain encourages routine screening for the
presence and intensity of pain in the clinical setting (36). Elicitation of a
pain complaint should indicate a more comprehensive assessment of pain, as
well as assess potential pain-related interference with social-role
functioning and compromised emotional well-being. Clinical assessment informed
by a multidimensional model such as the one in this article may lead to
greater attention to the complexity of psychosocial factors that can influence
the experience of pain and adjustment to pain. A more thorough assessment can
inform the development of a more comprehensive, multidisciplinary plan for
DIRECTIONS FOR FUTURE RESEARCH
There is strong empirical evidence that pain is a
prevalent problem among persons with MS. Unfortunately, reliable
characterizations of important aspects of pain in MS have only begun to be
investigated. Research in this area to date has relied entirely on relatively
small samples of patients attending specialized healthcare settings,
increasing the likelihood of biases in the collection of data. Such biases may
mask important characteristics of pain in MS, such as the distribution of
specific pain disorders across disease subtypes; relationships between pain
and other disease characteristics; and associations with important demographic
and descriptive variables such as age, gender, and race. Given findings from
the broader field of pain medicine, examination of the strength of the
contributions of pain to MS-related disability and psychosocial adjustment and
adaptation is also critically important targets for investigation.
The integrative model just presented may have heuristic
importance by encouraging attention to the complexities of interactions
between important biological, psychological, and social variables in
determining responses to pain and other symptoms of MS. The need for a
large-scale longitudinal epidemiologic study of persons with MS with a
specific focus on pain and uncomfortable parasthesias is clearly indicated.
Fortunately, such a study has been undertaken and preliminary results are
beginning to emerge (37).
There is also a continuing need for even smaller
cross-sectional studies of the experience of chronic pain in MS. Little is
known, for example, about factors that influence the intensity of pain
experienced, the development of pain-related disability and social-role
functioning, depressive symptom severity, and overall psychosocial adjustment
and adaptation. Studies are needed that investigate the relative contributions
of important disease parameters and key psychosocial constructs to the
experience of chronic pain in MS. Designs that employ rigorous sampling
methods, state-of-the-art measures of key constructs, and sophisticated
multivariate statistical procedures are essential.
There is a paucity of controlled trials of
rehabilitation (e.g., structured exercise) and psychological treatment (e.g.,
cognitive-behavior therapy) for pain in MS. Perhaps the lack of such research
is understandable given the paucity of research on MS-related pain and the
role of psychosocial factors, more generally. Also undoubtedly contributing to
the challenge of a controlled trial are factors related to the heterogeneity
and complexity of the disease itself (i.e., disease subtypes, type and
severity of symptoms, stage of the disease, and cognitive changes associated
with disease) and difficulties engaging a sample of persons with MS-related
pain large enough to ensure adequate power for examining treatment effects.
Nevertheless, such efforts will be important to expanding the availability of
these treatments for pain in MS.
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