The analgesic effect of acupuncture in neuropathic pain: regulatory mechanisms of DNA methylation in the brain

Abstract

Recent research has demonstrated that chronic pain, resulting from peripheral nerve injury, leads to various symptoms, including not only allodynia and hyperalgesia but also anxiety, depression, and cognitive impairment. These symptoms are believed to arise due to alterations in gene expression and neural function, mediated by epigenetic changes in chromatin structure. Emerging evidence suggests that acupuncture can modulate DNA methylation within the central nervous system, contributing to pain relief and the mitigation of comorbidities. Specifically, acupuncture has been shown to adjust the DNA methylation of genes related to mitochondrial dysfunction, oxidative phosphorylation, and inflammation pathways within cortical regions, such as the prefrontal cortex, anterior cingulate cortex, and primary somatosensory cortex. In addition, it influences the DNA methylation of genes associated with neurogenesis in hippocampal neurons. This evidence indicates that acupuncture, a treatment with fewer side effects compared with conventional medications, could offer an effective strategy for pain management.

Keywords: Acupuncture; Comorbidity; DNA methylation; Epigenetic mechanisms; Neuropathic pain.

Figure 1.

Summary of acupuncture's effect on chronic pain through DNA methylation. Peripheral nerve injury may cause changes in DNA methylation in the brain and, thus, may have a crucial role in chronic pain mechanisms. Acupuncture affects various brain areas by transmitting signals to the central nervous system through peripheral nerve stimulation. Acupuncture improves not only pain but also comorbidity, such as anxiety, depression, and cognitive impairments and induces changes in DNA methylation in ACC, S1, PFC, and HIP. Acupuncture modulates the expression of various genes by regulating the DNA methylation process–related proteins, such as DNMT3a, MeCP2, and TET1. ACC, anterior cingulate cortex; DNMT3a, DNA methyltransferase 3a; HIP, hippocampus; MeCP2, methyl-CpG-binding protein 2; PFC, prefrontal cortex; S1, primary somatosensory cortex; TET1, ten-eleven translocation 1.