Peripheral neuropathic pain is a complex disease, and treated based on underlying diseases. Emerging evidences suggest that hyperbaric oxygen alleviates neuropathic pain. However, its cellular and molecular mechanism on pain relief is unknown. We hypothesize that hyperbaric oxygen alleviates neuropathic pain via activating autophagy flux and inhibiting mTOR pathway. Hyperbaric oxygen effectively inhibited nerve injury induced autophagy impairment and mTOR pathway activation in a rat spinal nerve ligation (SNL) model. Moreover, intrathecal injection of rapamycin, an autophagy inducer, enhanced hyperbaric oxygen effect by further decreasing mTOR activity. In contrast, chloroquine, an autophagy inhibitor, counteracted hyperbaric oxygen analgesic effect. These findings indicate that hyperbaric oxygen attenuated neuropathic pain by increasing spinal autophagic flux via inhibiting mTOR pathway. Our study provides pre-clinical evidences in expediting hyperbaric oxygen become a safe clinical treatment of neuropathic pain.

Keywords: Spinal nerve ligation; autophagy; chloroquine; hyperbaric oxygen; mTOR; neuropathic pain.