Acupuncture alleviates inflammatory pain by regulating microglial polarization through alpha7nAchR-mediated autophagy
J Integr Med. 2026 Jan 28:S2095-4964(26)00007-5. doi: 10.1016/j.joim.2026.01.006. Online ahead of print.
ABSTRACT
OBJECTIVE: This study aimed to identify the optimal frequency of acupuncture for alleviating inflammatory pain and to explore the specific mechanisms through which it regulated microglial polarization.
METHODS: We first measured the frequency and angle of acupuncture manipulation using an acupuncture manipulation parameter sensor. An inflammatory pain model was induced in Sprague-Dawley rats via injection of complete Freund's adjuvant (CFA) to the hind paw. Using the previously developed acupuncture manipulation simulator, we delivered precisely controlled stimulation with three frequencies (1, 2 and 4 Hz) to the Zusanli (ST36) acupoint. The optimal frequency for relieving inflammatory pain was determined by assessing paw withdrawal threshold, withdrawal latency and oedema. The autophagy inhibitor 3-methyladenine (3-MA) and α7 nicotinic acetylcholine receptor (α7nAChR) antagonist methyllycaconitine (MLA) were intrathecally injected to inhibit microglial autophagy and α7nAChR activation, respectively. Western blotting was used to measure autophagy-related protein levels. Spinal microglial polarization was evaluated using immunofluorescence analysis. The levels of pro- and anti-inflammatory cytokines were measured using enzyme-linked immunosorbent assay. The changes of mitochondrial morphology of spinal microglia were observed with transmission electron microscopy.
RESULTS: The acupuncture manipulation simulator was used to precisely deliver treatments to CFA rats at three different frequencies with a rotation of 180°. Acupuncture manipulation at all three frequencies can effectively alleviate inflammatory pain and promote M2 polarization of the microglia, with 4 Hz acupuncture producing the best analgesic effect. The administration of 3-MA inhibited autophagy in spinal microglia, thereby reversing both the analgesic effect of acupuncture and its modulatory effect on microglial polarization. MLA markedly downregulated α7nAChR expression, inhibited autophagy, promoted M1 microglial polarization, and attenuated the analgesic effects of acupuncture. Moreover, acupuncture significantly decreased the expression of acetylcholinesterase.
CONCLUSION: Frequency of needle stimulation may be a critical factor influencing the analgesic efficacy of acupuncture. Acupuncture may mitigate inflammatory pain by promoting microglial polarization through α7nAChR-mediated autophagy. Please cite this article as: Dong GQ, Gao H, Sun YJ, Yang QH, Yao Y, Yang HY. Acupuncture alleviates inflammatory pain by regulating microglial polarization through α7nAchR-mediated autophagy. J Integr Med. 2026; Epub ahead of print.
PMID:41826216 | DOI:10.1016/j.joim.2026.01.006