Electroacupuncture intervention relieves pain by stimulating the STING/IFN-I pathway in rat models of cancer-induced bone pain.

Abstract

This study aimed to evaluate the effects of electroacupuncture (EA) on cancer-induced bone pain (CIBP) and investigate its interaction with the STING/IFN-I pathway. A CIBP model was established in female rats. EA was administered for six consecutive days at bilateral L3-L5 Jia Ji points (EX-B2). EA-induced antinociception was evaluated through mechanical, thermal, and cold sensitivity assessments. EA significantly increased the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in rats with CIBP (p < 0.01). In the spinal cord of CIBP model rats, western blot analysis demonstrated that the application of EA upregulated the expression of STING, IRF3, and IFNAR (p < 0.05). The ELISA results indicated that EA significantly increased the expression of IFN-α (p < 0.005) and IFN-β (p < 0.01) and reduced the expression of TNF-α and IL-1β (p < 0.05). Immunofluorescence analysis revealed that STING was predominantly localized in microglia, with a minimal presence in neuronal cells. Furthermore, intrathecal administration of the STING antagonist C-176 attenuated the analgesic effects of EA in CIBP (p < 0.05). Both EA and STING agonist were effective in alleviating pain in rats with CIBP, possibly through the activation of the STING/IFN-I pathway. Notably, EA treatment reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. In contrast, while the STING agonist exhibited analgesic effects, it was associated with elevated levels of pro-inflammatory cytokines. These finding underscore the therapeutic potential of EA in the management of CIBP.