Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats.

Hyperbaric oxygen (HBO) therapy is proven to attenuate neuropathic pain in rodents. The goal of the present study was to determine the potential involvement of the Kindlin-1/Wnt-10a signaling pathway during astrocyte activation and inflammation in a rodent model of neuropathic pain. Rats were assigned into sham operation, chronic constriction injury (CCI), and CCI + HBO treatment groups. Neuropathic pain developed in rats following CCI of the sciatic nerve. Rats in the CCI + HBO group received HBO treatment for five consecutive days beginning on postoperative day 1. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) tests were performed to determine mechanical and heat hypersensitivity of animals, respectively. Kindlin-1, Wnt-10a and β-catenin protein expression was examined by immunohistochemistry and Western blot analysis. Expression of tumor necrosis factor (TNF)-α was also determined by ELISA. Our findings demonstrated that HBO treatment significantly suppressed mechanical and thermal hypersensitivity in the CCI neuropathic pain model in rats. HBO therapy significantly reversed the up-regulation of Kindlin-1 in dorsal root ganglia (DRG), spinal cord, and hippocampus of CCI rats. CCI-induced astrocyte activation and increased levels of TNF-α were efficiently reversed by HBO (P < 0.05 vs. CCI). HBO also reversed Wnt-10a up-regulation induced by CCI in the DRG, spinal cord, and hippocampus (P < 0.05 vs. CCI). Our findings demonstrate that HBO attenuated CCI-induced rat neuropathic pain and inflammatory responses, possibly through regulation of the Kindlin-1/Wnt-10a signaling pathway.