cGAS-STING signaling in the anterior cingulate cortex modulates electroacupuncture analgesia in a rat neuropathic pain model.

Background: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is associated with different neurological dysfunctions in the nervous system. Although electroacupuncture (EA) has been proven to alleviate neuropathic pain (NP), its underlying mechanisms remain unclear. The role of the cGAS- STING signaling pathway in the anterior cingulate cortex (ACC) during NP and its potential association with EAmediated analgesic effects remain unknown. Methods: The authors established an NP model by applying chronic constriction injury (CCI) to the sciatic nerve and evaluated behavioral hyperalgesia using the acetone test score and mechanical threshold. Protein distribution and expression were assessed using immunofluorescence and Western blotting, respectively. Results: cGAS and STING were predominantly expressed in neurons in the ACC of rats, and the total abundance of cGAS and STING was upregulated on both sides of the ACC following CCI. Intra-ACC administration of either RU.521 or C-176 alleviated the pain hypersensitivity caused by CCI. Moreover, EA reduced pain hypersensitivity and inhibited the CCI-induced upregulation of cGAS and STING in the ACC. Conclusions: This study demonstrates that the cGAS-STING signaling pathway is involved in the occurrence and development of NP in the ACC following peripheral nerve injury, and that EA may alleviate NP by suppressing this pathway in rats.