Spinal cord injury (SCI) is a devastating condition that causes severe loss of motor, sensory and autonomic functions. Additionally, many individuals experience chronic neuropathic pain that is often refractory to interventions. While treatment options to improve outcomes for individuals with SCI remain limited, significant research efforts in the field of electrical stimulation have made promising advancements. Epidural electrical stimulation, peripheral nerve stimulation, and functional electrical stimulation have shown promising improvements for individuals with SCI, ranging from complete weight-bearing locomotion to the recovery of sexual function. Despite this, there is a paucity of mechanistic understanding, limiting our ability to optimize stimulation devices and parameters, or utilize combinatorial treatments to maximize efficacy. This review provides a background into SCI pathophysiology and electrical stimulation methods, before exploring cellular and molecular mechanisms suggested in the literature. We highlight several key mechanisms that contribute to functional improvements from electrical stimulation, identify gaps in current knowledge and highlight potential research avenues for future studies.
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.
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