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

Abstract

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. 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. 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). 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.