OBJECTIVE To explore the protective effect and mechanism of gallic acid(GA) on paclitaxel-induced peripheral neuropathy.

METHODS The primary dorsal root ganglion (DRG) was extracted to establish an in vitro model of paclitaxel-induced DRG cell injury; CCK-8 assay was used to evaluate the neuroprotective effects of GA on this model. The paclitaxel-induced neuropathic pain model in C57BL/6J mice was established, and the behavioral test was used to analyze effects of GA alleviating paclitaxel-induced peripheral neuropathy and to explore whether GA alleviated paclitaxel-induced peripheral neuropathic pain by inhibiting the activation of NLRP3 inflammatory and reducing the release of pro-inflammatory cytokine. qPCR was used to detect the expression levels of NLRP3, Caspase-1, and IL-1β mRNA in DRG cells; Western blot was used to detect the change of protein levels of NLRP3, Caspase-1, and IL-1β; and the fluorescence intensity of NLRP3, Caspase-1, and IL-1β proteins was analyzed by immunofluorescence staining.

RESULTS GA exerts a protective effect and improved the survival rate of paclitaxel-stimulated DRG cells; reduced mechanical, cold and thermal pain hyperalgesia in mice; effectively reversed the elevated expression levels of NLRP3 and Caspase-1 in paclitaxel-stimulated DRG cells and reduced the release of pro-inflammatory cytokine IL-1β, which ameliorated the neuroinflammatory response induced by paclitaxel.

CONCLUSION Gallic acid improves paclitaxel-induced neuroinflammation by regulating the NLRP3 inflammasome pathway. The NLRP3/Caspase-1/IL-1β pathway is one of the potential mechanisms for the treatment of paclitaxel-induced peripheral neuropathy.