Perceived pain during isometric exercise and neuromuscular fatigability in individuals with multiple sclerosis

Among people with multiple sclerosis (PwMS), pain is a common symptom, and neuromuscular fatigability is widely reported. However, the association between pain during exercise and neuromuscular fatigability remains unclear. This study aimed to identify the association between perceived pain and neuromuscular fatigability during an exercise task in PwMS. Thirty-two PwMS (age=56.4, females=15) and 15 age- and sex-matched non-MS controls (age=57.9, females=7) participated. Disease severity was evaluated using the Expanded Disability Status Scale (median EDSS=4.0). The experimental protocol involved maximal voluntary contractions (MVCs) of the dorsiflexors, time-to-task failure (TTF) of an isometric fatiguing exercise sustained at maximal strength (neuromuscular fatigability), and a post-exercise MVC. Central and peripheral fatigability were assessed using electrical stimulation. The twitch interpolation technique quantified voluntary activation (VA), with pre-to-post exercise reductions in VA indicating central fatigability. Pre-to-post exercise reductions in resting twitch amplitude indicated peripheral fatigability. Perceived pain (0-10) was assessed at rest prior to exercise, during, and immediately post-exercise. Associations of changes in pain perception were identified using Spearman's correlation coefficient (rho). Despite no significant differences between PwMS and controls across all outcome measures (p > 0.2), compared to controls, PwMS with higher disease severity (n = 12, EDSS≥4.5) had a significantly shorter TTF (mean difference=-38.5 s, p = 0.04), higher central fatigability (11 percentage points, p = 0.01), and lower peripheral fatigability (-20.8%, p = 0.01). Among PwMS, smaller changes in pain perception correlated with increased neuromuscular fatigability (rho=0.5, p = 0.003), higher central fatigability (rho=-0.4, p = 0.05), and lower peripheral fatigability (rho=0.4, p = 0.03). These findings suggest that perceived pain during the exercise task may be an overlooked mechanism contributing to neuromuscular fatigability in PwMS.