Differential Structural Brain Changes Between Responders and Nonresponders After Physical Exercise Therapy for Chronic Nonspecific Neck Pain

Abstract

Objectives: Physical exercise therapy is effective for some people with chronic nonspecific neck pain but not for others. Differences in exercise-induced pain-modulatory responses are likely driven by brain changes. We investigated structural brain differences at baseline and changes after an exercise intervention. The primary aim was to investigate changes in structural brain characteristics after physical exercise therapy for people with chronic nonspecific neck pain. The secondary aims were to investigate (1) baseline differences in structural brain characteristics between responders and nonresponders to exercise therapy, and (2) differential brain changes after exercise therapy between responders and nonresponders.Materials and Methods: This was a prospective longitudinal cohort study. Twenty-four participants (18 females, mean age 39.7 y) with chronic nonspecific neck pain were included. Responders were selected as those with ≥ 20% improvement in Neck Disability Index. Structural magnetic resonance imaging was obtained before and after an 8-week physical exercise intervention delivered by a physiotherapist. Freesurfer cluster-wise analyses were performed and supplemented with an analysis of pain-specific brain regions of interest.Results: Various changes in grey matter volume and thickness were found after the intervention, for example, frontal cortex volume decreased (cluster-weighted P value = 0.0002, 95% CI: 0.0000-0.0004).We found numerous differences between responders and nonresponders, most notably, after the exercise intervention bilateral insular volume decreased in responders, but increased in nonresponders (cluster-weighted P value ≤ 0.0002).Discussion: The brain changes found in this study may underpin clinically observed differential effects between responders and nonresponders to exercise therapy for people with chronic neck pain. Identification of these changes is an important step toward personalized treatment approaches.

Exercise Therapy for Chronic Neck Pain: Tailoring Person-Centred Approaches within Contemporary Management

“…Because these sensitivity changes are typically related to the central nervous system, it is likely that central neurophysiological mechanisms play a role in these differential responses to physical exercise therapy [61]. Indeed, a recent study investigating brain changes after physical exercise therapy found differential structural brain changes between responders and nonresponders to the exercise program [31]. Furthermore, structural differences were already present at baseline, further supporting the notion of differential central neurophysiological mechanisms.…”

“…Whilst numerous factors may contribute to this (e.g., the lack of adherence and variability in exercise programs), a proportion of people with neck pain may experience worsened pain following exercise therapy. Indeed, in a recent study [31] with high adherence to the exercise program, just over half of the participants (n = 13/24 (54%)) were found to experience clinically meaningful improvements (>20% improvement in pain-related disability). Whilst these findings are yet to be replicated, it is known that people with neck pain due to fibromyalgia are more likely to experience worsening of symptoms after exercise due to increased reactivity [32].…”

“…The reasons why some individuals respond positively while others do not remain unclear; however, there may be different underlying mechanisms contributing to these differential responses. Central nervous system changes in patients with chronic neck pain could potentially explain these variations, as suggested by a recent study that found different brain changes in responders and nonresponders after exercise therapy [31]. This raises the questions of whether there are clinical subgroups among people with chronic neck pain and whether their response to exercise therapy is related to these subgroups.…”

“…Although the physiological effects of exercise have been widely described in healthy populations, there are likely to be differences across people with chronic neck pain. In fact, evidence has shown that the differential effects of different types of exercise and the differences between patients may possibly be related to their differential physiological effects [31,38,61]. Some people with chronic neck pain may respond to exercise therapy with a decrease in pain sensitivity, known as exercise-induced hypoalgesia (EIH).…”

“…At the same time, this means trialling other types of treatment for those patients for whom exercise therapy is not effective. Emerging evidence is becoming available suggesting methods to provide a meaningful prediction of the therapeutic effectiveness in chronic pain populations [31,84]. Improvements in prediction capabilities will enhance targeted and personalised pain medicine and will likely inform who would benefit most from exercise therapy for chronic neck pain.…”