Date of Award

Spring 2024

Document Type


Degree Name

Doctor of Physical Therapy (DPT)


Physical Therapy

First Advisor

Alexander Ng


Subjective fatigue and pain are commonly reported in people with MS (pwMS), as is neuromuscular fatigability. The dynamometry protocols used to measure neuromuscular fatigability in pwMS varied substantially in terms of components, leading to inconsistent findings regarding the extent of neuromuscular fatigability and its central and peripheral mechanisms in pwMS compared to non-MS controls. This dissertation aimed to compare neuromuscular fatigability and its underlying mechanisms following a sustained maximal to intermittent submaximal ankle dorsiflexion in pwMS, grouped by disease severity, and non-MS controls. Additionally, we aimed to determine the impact of physical activity, muscle oxidative capacity, and exercise-induced pain on neuromuscular fatigability and to classify pain phenotypes in pwMS. The time-to-task failure (TTF) of the fatiguing exercise was measured to quantify neuromuscular fatigability. Peripheral electrical stimulation was utilized to quantify central and peripheral mechanisms. Physical activity was measured by accelerometry. Oxidative capacity was assessed using the Near Infrared Spectroscopy. Pain surveys and measures of somatosensory function were conducted for pain classification. The key findings of this dissertation were that: 1) Neuromuscular fatigability was task-dependent in pwMS, as with controls, and was associated with disease severity. The TTF of sustained exercise was shorter than intermittent exercise in all participants. Overall, pwMS with higher disease severity exhibited shorter TTF than individuals with lower disease severity and controls. 2) Overall, pwMS exhibited both central and peripheral limitations during exercise, which were affected by the type of exercise and disease severity. This contrasted with controls, who only experienced peripheral limitations. Central limitations in pwMS were not affected by the type of exercise. However, peripheral limitations were more pronounced in response to intermittent exercise than sustained exercise. Overall, pwMS with higher disease severity experienced greater central but lower peripheral fatigability compared to those with lower disease severity and controls. 3) Lower physical activity and reduced oxidative capacity were related to increased neuromuscular fatigability in pwMS. Smaller change in pain during exercise was related to increased neuromuscular fatigability in pwMS, possibly via a pain-avoidance strategy. Further, pain types were mixed in pwMS, including elements of nociceptive, neuropathic, and nociplastic pain phenotypes.

Available for download on Thursday, May 22, 2025