Bone marrow mesenchymal stem cells attenuate pain and modulate peripheral sodium channel activity in a rat model of complex regional pain syndrome type I.

Complex Regional Pain Syndrome Type I (CRPS-I) is a chronic neuropathic pain disorder characterized by peripheral nerve hyperexcitability and altered nociceptive signaling. Voltage-gated sodium channels (Nav1.7, Nav1.8, Nav1.9) in dorsal root ganglia (DRG) are key contributors to pain hypersensitivity. This study investigated the analgesic effects and underlying mechanisms of bone marrow mesenchymal stem cell (BMSC) transplantation in a CRPS-I rat model. The model was induced by hind limb ischemia-reperfusion, followed by intrathecal administration of BMSCs. Pain behaviors were assessed using thermal withdrawal latency (TWL), mechanical withdrawal latency (MWL), spontaneous pain scoring, and acetone-evoked cold allodynia. RT-PCR and Western blot analysis were used to evaluate Nav channel expression in DRG tissue, while electrophysiological properties were examined using whole-cell patch clamp to generate current-voltage (I-V) curves. CRPS-I rats exhibited decreased TWL and MWL, elevated expression of Nav1.7, Nav1.8, and Nav1.9, and enhanced sodium current density with delayed inactivation. BMSC transplantation significantly alleviated pain behaviors, downregulated sodium channel expression, and normalized I-V characteristics-marked by increased activation thresholds, reduced peak currents, and faster inactivation kinetics. These findings suggest that BMSCs mitigate neuronal hyperexcitability by modulating peripheral Nav channel activity. This study provides mechanistic evidence supporting the therapeutic potential of BMSC-based interventions for CRPS-I and related neuropathic pain conditions.