Fibromyalgia (FM) is a complex condition, characterized by chronic musculoskeletal pain along with a host of other interrelated symptoms. Although the mechanisms that maintain pain in FM are unknown, evidence points to a central nervous system dysregulation of pain processing. Specifically, research demonstrates heightened sensitivity to sensory stimuli, exaggerated brain responses to both painful and non-painful stimuli, and impairments in pain modulation [1
The ability to modulate pain is critical for maintaining a functional balance between facilitation and inhibition of sensory stimuli and dysregulations in pain modulation can influence quality of life, disability and the development of chronic pain [2
]. Exercise stimulates the pain modulatory system [3
] and chronic aerobic exercise training is a consistently efficacious treatment for FM [4
]. It is plausible then that exercise functions as a treatment by improving pain modulation. Previous research has examined the relationship between exercise and pain modulation in FM. However, current evidence is equivocal with some studies showing a decrease in pain sensitivity with exercise and others showing either no change or an increase [5
]. Brain responses to pain following exercise remain largely unexplored in FM. A better understanding of these responses could help to explain the consequences of acute and chronic exercise for FM patients.
The purpose of the present study was to assess the influence of exercise on brain responses to pain in patients with FM and pain-free controls. Exercise was used as a method of stimulating pain modulatory (i.e., central nervous) systems in FM and functional neuroimaging was employed to explore the neural responses underlying these processes.
This study examined brain responses to pain post-exercise in FM patients and pain-free controls using functional neuroimaging. Our results demonstrated that a short bout of moderate intensity cycling resulted in temporary improvements in centrally mediated pain modulation in FM patients. Notably, both brain responses and pain ratings for FM patients were similar to those of controls immediately post-exercise. However, pain ratings for FM were lower following exercise compared to quiet rest and this was accompanied by an increase in activity among brain regions involved in pain modulation [1
]. We also observed a significant relationship between changes in DLPFC brain activity and changes in pain perception. Overall, these results suggest that a moderate intensity bout of acute exercise can influence descending regulatory systems in FM. Considering that exercise has been shown to be an efficacious treatment for FM, these results suggest that symptom improvements in FM following exercise training may be, in part, the result of increases in the functional capacity of the pain modulatory system.
Differences were seen in the anterior insula comparing exercise to quiet rest for FM patients and there were differences both within and between groups in the DLPFC, brain regions that are strongly implicated in pain modulation [21
]. The anterior insula has been classified as a primary component of the pain salience network [23
] and several studies have highlighted the insula as a critical brain region discriminating FM from healthy controls [22
]. Activity in the DLPFC is also strongly implicated in pain modulation [24
] and previous data from our group demonstrated that activity in this region was negatively associated with sedentary behavior and pain modulation in FM patients [25
]. This suggests that modifiable behaviors such as prolonged sitting and/or physical activity may impact pain modulation. Our present results are in-line with those demonstrating that following quiet rest, which likely represents typical neuroimaging conditions, patients had decreases in activity in this region in comparison to baseline. Further, following exercise, patients showed small increases in brain activity from baseline; a response that was consistent with brain responses in healthy controls at rest.
Previous research regarding the effects of acute bouts of exercise on pain sensitivity in FM patients is largely equivocal. Some studies have demonstrated a hypoalgesic effect [5
] while other studies show either no changes in pain perception or an exacerbation of pain [27
]. With respect to exercise training, the results are more consistent and a large body of evidence now demonstrates that regular exercise is beneficial for FM [4
]. However, the mechanisms that drive these benefits are largely unknown. Our results suggest that moderate intensity exercise can stimulate central pain regulatory mechanisms. Notably, we found that exercise results in beneficial alterations of both pain perception a brain responses to pain for approximately 20–30 min post-exercise. While temporary, these improvements may become more permanent with repeated exposure (i.e.
, a positive adaptation to chronic exercise) and may provide mechanistic insight into the efficacy for exercise training in the treatment of FM. In support of this contention is recent evidence that six weeks of aerobic exercise training increased ischemic pain tolerance in healthy individuals [30
] and that physical activity is related to pain modulation in both healthy individuals and FM [31
]. How these results translate to exercise training in patients with chronic pain is currently unknown. Clinical trials determining whether exercise training can strengthen central pain modulation and whether these changes are associated with symptom improvements are needed to more fully test this hypothesis.
There was also a difference in brain responses for controls between exercise and quiet rest conditions in the right parietal operculum and in an area spanning the right pre- and postcentral gyri, areas contralateral to the pain stimulus. These regions are consistently active in response to nociceptive stimuli and are known to have somatotopic organization suggesting that they encode spatial aspects of pain processing [21
]. Controls had greater activity in these regions post-exercise compared to quiet rest demonstrating that exercise influenced these areas. Previous research has also demonstrated their involvement in pain post-exercise as a function of delayed onset muscle soreness [34
]. However, pain ratings did not differ between conditions in controls making a conclusive interpretation of these results difficult. Future studies in healthy individuals where exercise intensity is high enough to induce a hypoalgesic response will be critical for the further exploration of the influence of exercise on a typically-functioning central nervous system.
This study had a number of limitations. We included a small sample of patients and controls and our sample included only women, limiting the generalizability of our findings. Further, we excluded individuals with diagnosed mental health conditions and those who were taking medications that could impact pain or the interpretation of brain responses. As such, our results may not apply to FM patients with comorbid conditions. However, our group of patients had FIQ scores and levels of physical activity and sedentary behaviors that are comparable to those previously reported in FM patients [8
]. Further, we intentionally chose a moderate intensity exercise stimulus in order to ensure that our patients would be able to complete the exercise protocol and chose to keep the relative intensity consistent between groups to improve comparability. However, it appears that the exercise bout as prescribed was not a sufficient stimulus to induce a decrease in pain sensitivity in our pain-free controls. This is consistent with previous literature regarding the effects of acute exercise on pain in healthy controls, which typically finds that higher intensity exercise is necessary to elicit a hypoalgesic response [35
]. Thus, we were unable to compare brain responses during exercise-induced hypoalgesia between groups.
Our study also had a number of notable strengths. Most importantly, we used functional neuroimaging to examine brain responses to pain relatively soon post-exercise allowing us to explore the acute effects of exercise on central nervous system responses. As part of this process, we measured and statistically controlled for the physiological effects of exercise that could impact the BOLD response. Though the evidence is equivocal, it has been suggested that cardiovascular mechanisms may be involved in the hypoalgesic response to exercise [36
] and, thus statistically controlling for these effects may have influenced the interpretation of our results. However, without controlling for physiological differences between EX and QR the data would have been difficult to interpret. Lastly, we used an objective measure to assess physical activity to confirm that our sample had typical levels of physical activity for this population [37
A growing number of studies have begun to employ neuroimaging methods to better understand the impact of exercise on the brain both longitudinally and acutely. For example, Smith and colleagues [39
] conducted fMRI scans before and after an exercise training program in older adults with mild cognitive impairment and found that exercise improved neural efficiency during cognitive tasks post-intervention. Structural MRI has also been used to show the neuroprotective effects of regular exercise in older adults with respect to preservation of brain volume [40
]. In contrast to using neuroimaging to track changes in the brain over time, neuroimaging during and immediately following exercise presents some unique challenges due to artifacts associated with movement and the physiological underpinnings of many neuroimaging methods (e.g., BOLD response). EEG has been used most extensively to explore the effects of exercise on cortical activity [41
]. PET and fMRI have also been used, though to a much lesser extent. For example, Boecker and colleagues [42
] used PET to demonstrate the effects of a long-distance run on opioid release in the brain and Janse Van Rensberg and colleagues [43
] used fMRI to examine brain responses to nicotine craving following 10 min of moderate intensity cycling. Our study adds to this important body of literature by using fMRI to show that an acute bout of moderate intensity exercise improved brain mechanisms underlying pain modulation in patients with chronic pain and further highlights the potential benefits of utilizing neuroimaging technology to better understand the more immediate effects of exercise on the human brain.