Cognitive-behavior Therapy for MS-Related Chronic Pain

The primary purpose of the proposed study is to evaluate the feasibility and efficacy of
tailored CBT with standard pharmaceutical care (CBT/SC) in reducing pain, disability, and
distress among persons with Multiple Sclerosis (MS) related pain conditions. This will
entail: (1) evaluating the feasibility, perceived credibility, participation and adherence
rates, and satisfaction related to CBT, (2) conducting a randomized controlled trial of the
efficacy of CBT relative to an education control/standard care (ED/SC) condition, and (3)
evaluating possible predictors of treatment response including demographics,
disease-relevant variables, cognitive functioning, and motivation or readiness to adopt a
self-management approach to MS-related pain.

Research Design: A randomized mixed factorial controlled design will be employed in which
CBT/SC is compared to EDSC. Repeated assessments of key outcome domains will occur at
pretreatment/baseline, at 15 weeks (post-treatment), and 20, 36, and 52 (follow-up) weeks.

Methodology: Participants in this trial will be 124 persons with MS (including veterans and
non-veterans) who report persistent MS-related pain (e.g., neuropathic pain, pain related to
muscle spasms, neuralgias) of at least moderate intensity (pain severity of 4 or greater on
the numeric rating scale) despite optimal pharmacological management. Participants must be
at least 21 years of age and able to provide informed consent. Exclusion criteria include:
(1) pending surgery or interventional anesthesiological procedures for pain, (2) currently
psychotic or actively suicidal or homicidal, (3) current alcohol or substance abuse or
dependence, (4) presence of other life threatening illnesses, (5) the presence of profound
cognitive impairment rendering successful participation in CBT or ED impossible, (6) the
presence of physical disabilities resulting in an inability to attend treatment sessions
and/or inability to participate in telephone interventions (e.g., severe dysarthria), (7)
prior or current psychological treatment for chronic pain, (8) two or more documented
exacerbations of MS-related symptoms during the past year, and (9) current exacerbation of
symptoms defined as sudden onset of symptoms within a 24 hour period. CBT will involve an
innovative treatment approach that combines specific training in relevant cognitive and
behavior skills targeting management of pain and the negative impacts of pain. The
application of these skills for the management of coincident symptoms of MS (e.g.,
spasticity, fatigue, abnormal sensory experiences) will also be encouraged. ED will involve
provision of a broad array of educational material regarding MS and its management, but it
will not explicitly inform participants about non-pharmacological strategies for management
of pain. Both treatments will involve seven 60 minute, outpatient individual treatment
sessions offered every other week, interspersed with five, 30 minute individual telephone
sessions (one final face-to-face session will be 30 minute individual telephone sessions
will be included) provided by a psychologist and supported by patient education and
treatment guides that have been developed for the study. Participants will be randomly
assigned to one of two treatment arms: CBT/SC or ED/SC. Recruitment rates, session
adherence, dropout rates, and participants' ratings of comprehension, treatment credibility,
treatment satisfaction and adherence to therapist recommendations will be used to assess
feasibility of the treatment and recruitment methods. Multiple standardized measures of each
outcome domain of interest will be obtained, including pain severity, disability, affective
distress, and quality of life. The analysis of each of the primary and secondary outcome
measures (summary measures of pain intensity, pain-related disability, MS-related
disability, and emotional functioning) will be by a repeated measures mixed effects model27.
The outcome variable in each model will be the changes at each follow-up visit relative to
baseline, with the baseline value included as a covariate in the model. Several possible
predictors of treatment adherence and outcome will be examined, including participant
demographics (e.g., age, gender, ethnicity), disease-relevant variables (e.g.., MS subtype,
disease duration, disease severity, level of cognitive functioning), outcome measures (e.g.,
pain severity, depressive symptom severity), and a measure of motivation for adoption of a
self-management approach to chronic pain.

Inclusion Criteria:

- a confirmed diagnosis of Multiple Sclerosis,

- history of daily pain or discomfort (burning, tingling or other parenthesis) for a
period of 3 months immediately prior to enrollment,

- judgment of one of the study neurologists (AL or MK) that the pain reported by the
patient is either directly [e.g., pain associated with optic neuritis and neuralgias]
or indirectly related [e.g., pain due to painful muscle contractures and spasms] to
MS and/or its treatment (persons with pain that is judged to be entirely coincident
with MS [e.g., idiopathic low back pain] will not be included),

- documentation of optimal pharmacological management of MS-related pain and
confirmation of this judgment by one of the study neurologists,

- continued use of appropriate pharmaceuticals for the management of MS and pain, and

- continued refractory pain despite pharmaceutical intervention as described above (as
determined by a pain intensity score 4 on a 0-10 numeric rating scale).

Exclusion Criteria:

- pending surgery or interventional anesthesiological procedures for pain,

- currently psychotic or actively suicidal or homicidal,

- current alcohol or substance abuse or dependence,

- presence of other life threatening illnesses,

- the presence of profound cognitive impairment rendering successful participation in
CBT or ED impossible,

- the presence of physical disabilities resulting in an inability to attend treatment
sessions and/or inability to participate in telephone interventions (e.g., severe
dysarthria),

- prior or current psychological treatment for chronic pain,

- two or more documented exacerbations of MS-related symptoms during the past year, and

- current exacerbation of symptoms defined as sudden onset of symptoms within a 24 hour
period. Participants experiencing an exacerbation will be included after a one-month
period of appropriate treatment or three months after the onset of the exacerbation.
The Exacerbation Questionnaire, also described below and developed by Dr. Mohr, one
of our co-investigators, will be used to assess and monitor significant exacerbations
of MS. The Multiple Sclerosis Functional Composite (MSFC) score described below will
be used to determine these later two exclusion criteria.