Exercise alleviates allodynia and hyperalgesia concomitant with improvements in aberrant primary afferents and spinal circuit inhibition in the dorsal horn of rats with incomplete spinal cord injury.

Neuropathic pain (NP) is a common complication following spinal cord injury (SCI), significantly impairing patients' physical/mental health and quality of life. While activity-based exercise has demonstrated efficacy in alleviating SCI-NP in rodent models, the mechanisms underlying this effect remain unclear. Specifically, it requires investigation whether exercise mediates its benefits through the following mechanisms: improving aberrant primary afferents and circuit inhibition in the lumbar dorsal horn after thoracic contusion SCI. In this study, we implemented an exercise training protocol in rats with incomplete thoracic SCI. We evaluated its effects on several factors, including mechanical withdrawal thresholds (MWTs), thermal withdrawal latencies (TWLs), and rate-dependent depression (RDD) of H-reflex. Additionally, we examined the changes in vesicular glutamate transporter 1 (VGluT1, specifically labeled in myelinated primary afferent terminals), calcitonin gene-related peptide (CGRP)-labeled nociceptive unmyelinated primary afferents, glutamic acid decarboxylase 65+67 (GAD 65+67), and potassium-chloride cotransporter 2 (KCC2). Our results showed that exercise training significantly improved MWTs and TWLs, enhanced the RDD of H-reflex, increased the synthesis of VGluT1, GAD 65+67, and KCC2 within the spinal dorsal horn, while reducing the CGRP-labeled nociceptive unmyelinated primary afferents. These findings indicate that exercise alleviates mechanical allodynia and thermal hyperalgesia, which is paralleled by improvements in aberrant primary afferents, enhanced RDD of the H-reflex, and increased synthesis of GAD 65+67 and KCC2 in the lumbar dorsal horn following thoracic contusion SCI.