Lower corticospinal excitability and greater fatigue among people with multiple sclerosis experiencing pain

Abstract

Introduction: Persons with multiple sclerosis (MS) frequently report pain that negatively affects their quality of life. Evidence linking pain and corticospinal excitability in MS is sparse. We aimed to (1) examine differences in corticospinal excitability in MS participants with and without pain and (2) explore predictors of pain.

Methods: Sixty-four participants rated their pain severity on a visual analog scale (VAS). Transcranial magnetic stimulation (TMS) and validated clinical instruments characterized corticospinal excitability and subjective disease features like mood and fatigue. We retrieved information on participants' prescriptions and disability status from their clinical records.

Results: Fifty-five percent of participants reported pain that affected their daily functioning. Persons with pain had significantly greater fatigue and lower area under the excitatory motor evoked potential (MEP) recruitment curve (eREC AUC), a measure of total corticospinal excitability. After controlling for age, disability status, and pain medications, increased fatigue and decreased eREC AUC together explained 40% of the variance in pain.

Discussion: Pain in MS is multifactorial and relates to both greater fatigue and lesser corticospinal excitability. Future work should better characterize relationships between these outcomes to develop targeted pain interventions such as neuromodulation.

Summary: We examined pain in MS. Individuals with pain had higher fatigue and lower corticospinal excitability than those without pain. These outcomes significantly predicted self-reported pain.

Keywords: Corticospinal excitability; motor evoked potential; multiple sclerosis; pain; transcranial magnetic stimulation.

Figure 1.

Flowchart of participant enrollment, allocation, and analysis. We recruited 102 consecutive participants volunteers from a local MS clinic who agreed to take part in a longitudinal MS cohort study. Inclusion criteria were: (1) diagnosis of MS and (2) age 18 years of age or older. We excluded participants with (1) absolute contraindications to TMS, (2) history of active disease or systemic corticosteroid use in the last 3 months, (3) no pain self-report, or (4) incomplete TMS testing which prevented data analysis. We excluded three individuals who did not complete pain self-reports. Another 35 did not complete TMS testing, preventing data analysis. We included 64 participants for data analysis. Twenty-nine participants (45%) did not report having pain (no pain group), and 35 (55%) reported pain that had a functional impact on their life (pain group).

Figure 2.

Comparison of total corticospinal excitability (excitatory motor evoked potential [MEP] recruitment curve, eREC) in participants with (dark gray) and without pain (light gray). A. MEP recruitment curves exhibiting TMS stimulator intensity (percentage of active motor threshold [% AMT]; x-axis) raw MEP amplitude (µV; y-axis). Plot shows individual data points with larger circles depicting the group means. B. Boxplot showing groupwise comparison of eREC area under the curve (AUC). Plots include individual data points, means (×) and medians (horizontal line), interquartile ranges (boxes), and 95% confidence intervals (error bars). A Mann–Whitney U test on eREC AUC values showed that persons without pain had significantly greater total corticospinal excitability (p = .019), although the effect size was small (r = 0.29).