Authors : Rahul R. K.; Aswathy M.

Volume/Issue : Volume 11 - 2026, Issue 8 - August

Google Scholar : https://tinyurl.com/53hyc8bw

Scribd : https://tinyurl.com/2dcr9jny

DOI : https://doi.org/10.38124/ijisrt/26aug237

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Abstract : Background: DNA methylation is a plausible mechanism through which acupuncture might produce persistent analgesic effects, but association, pathway involvement, and causal mediation are often conflated.  Objective: To systematically review preclinical and clinical evidence on whether DNA methylation mediates acupuncture analgesia.  Methods: PubMed/MEDLINE and Europe PMC were searched from inception to May 2026. Eligible original studies evaluated acupuncture or electroacupuncture, reported pain or nociceptive outcomes, and directly measured DNA methylation or experimentally investigated methylation-related machinery. Two reviewers independently conducted study selection, data extraction, and risk-of-bias assessment, with disagreements resolved by consensus. Owing to methodological heterogeneity, the findings were synthesized narratively.  Results: The searches retrieved 132 database records; 62 duplicates were removed, 70 unique records were screened, 13 reports underwent eligibility assessment, and four studies were included. All four were animal studies; no eligible clinical analgesia study was identified. In neuropathic-pain mice, manual acupuncture altered region-specific global methylation and prefrontal-cortex methylome patterns while reducing allodynia. In a tibial-nerve-injury model, electroacupuncture reduced contralateral S1 5mC alongside improved mechanical thresholds. A TET1/Prox1 demethylation pathway supported durable antidepressant effects in pain-comorbid mice but was explicitly unrelated to nociception. A rat study functionally implicated a DNMT3a/MOR pathway, yet did not directly measure CpG methylation. No study performed formal mediation analysis or a methylation-specific rescue experiment that established necessity and sufficiency for acupuncture analgesia.  Conclusions: Current evidence is consistent with acupuncture-associated, tissue-specific methylation remodeling during neuropathic pain, but is insufficient to conclude that DNA methylation mediates analgesia. The Overall confidence in a causal mediation effect remains very low., and the clinical evidence base is absent.

Keywords : Acupuncture; Electroacupuncture; Analgesia; Neuropathic Pain; DNA Methylation; DNMT3a; TET1; Epigenetics.

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