Antinociceptive role of IL-10/STAT3 signaling in trigeminal neuropathic pain male rat model through Pomc and β-endorphin.

Abstract

Interleukin-10 (IL-10) is a cytokine that can exert an analgesic effect on trigeminal neuropathic pain (TNP). However, its precise mechanism remains unclear. In this study, we investigated the antinociceptive effects of recombinant IL-10 (rIL-10) in a rat model of infraorbital nerve constriction. Using male Sprague-Dawley rats, we administered rIL-10 or phosphate-buffered saline to the intra-trigeminal ganglion and observed a peak analgesic effect at 4 h post-injection in the rIL-10 group. Real-time PCR demonstrated significant upregulation of the Proopiomelanocortin (Pomc) gene in rIL-10-treated rats, with immunofluorescence staining confirming increased expression of bioactive peptide β-endorphin (β-END) in the same group. In situ hybridization assay further localized Pomc expression to satellite glial cells and neurons in the trigeminal ganglion, with β-END exhibiting a similar distribution. To elucidate the signaling mechanism, we co-administered a STAT3 inhibitor, Stattic, which abolished the analgesic effect of rIL-10, suppressed Pomc upregulation, and reduced β-END expression. These findings indicate that the STAT3 pathway is a critical mediator of rIL-10-induced analgesia, with Pomc and β-END as potential molecular effectors.