Investigating the Impact of Exercise Training on Pain Sensitivity in Veterans with Chronic Widespread Pain by Gunnar A. Roberge A thesis submitted in partial fulfillment of the requirement for the degree of Master of Science (Kinesiology) at the UNIVERSITY OF WISCONSIN-MADISON 2025

Abstract

Chronic pain is a leading cause of disability worldwide and its prevalence continues to rise (Grol-Prokopczyk, 2017; James et al., 2018; Rice et al., 2016). The pain that most patients experience can often be attributed to an underlying condition such as osteoarthritis, in which the pain is–at least initially–driven by ongoing nociceptive inputs from damaged tissue or persistent inflammation (i.e., nociceptive pain). Pain can also result from damage to the somatosensory nervous system (i.e., neuropathic pain) caused by diseases such as postherpetic neuralgia or multiple sclerosis. However, there are several conditions in which the patients’ pain cannot be explained by any identifiable tissue damage or nervous system injury. Common examples of these conditions include fibromyalgia syndrome, irritable bowel syndrome, chronic fatigue syndrome, temporomandibular disorder, migraine, and Gulf War illnesses. Many of these patients also experience fatigue, cognitive dysfunction, and several additional symptoms. To begin addressing certain gaps in the literature, our group conducted a randomized controlled trial (RCT) examining the effects of a 16-week resistance exercise training (RET) intervention on clinical symptoms, physical performance, experimental pain ratings, physical activity, and neuroimaging outcomes in Gulf War veterans with chronic widespread pain compared to a waitlist control (WLC) group. In addition to evaluating the safety and efficacy of RET for this population, the overall trial included several exploratory aims designed to investigate potential mechanisms underlying any observed effects. One of these aims was to investigate the effects of exercise training on sensory sensitivity. This was assessed by recording participants’ pain intensity and unpleasantness ratings in response to noxious thermal stimuli delivered during functional magnetic resonance imaging (fMRI) sessions. These thermal stimuli included three absolute temperatures (45.0℃, 47.0℃, & 48.9℃) and one relative temperature that elicited “moderate” to “slightly intense” pain (11-13 on our pain intensity scale) for each individual participant at baseline. In this thesis, I

begin to address this aim by determining whether the RET intervention influenced the level of pain induced by these stimuli, with the hypothesis that participants in the RET group would report lower pain intensity and unpleasantness ratings over the course of the trial compared to those in the WLC group. The results of this thesis will contribute to a better understanding of the relationship between exercise and hypersensitivity within the central nervous system. In the long term, this line of research aims to clarify the pathophysiological mechanisms driving chronic multisymptom illnesses such as fibromyalgia syndrome and Gulf War illness, and to inform the development of effective treatments for these conditions.