Medical Research

Electroacupuncture Exerts Analgesic Effects on Chronic Pain by Restoring Hyperactivity via Cannabinoid Type 1 Receptors in the Anterior Cingulate Cortex in Chronic Inflammatory

Kristen Sparrow • April 30, 2024

painWe know that acupuncture activates endorphins which help decrease pain, and that it also stimulates the vagus nerve from the periphery to the brainstem signalling the vagus.  But this mechanism outlined in this study highlights the role of the brain on chronic pain in a specific brain regions with specific endocannabinoids.  Point used was Stomach 36 with electro.

Chronic pain involves hyperactive neurons in the anterior cingulate cortex (ACC), but the role of cannabinoid type 1 receptors (CB1Rs) in EA analgesia is unclear.

This study explored CB1R involvement in EA analgesia mechanisms. It found that EA at the Zusanli acupoint (ST36) reduces ACC neuron hyperactivity by increasing endocannabinoids and CB1R expression.

CB1R activation negatively regulates N-methyl-D-aspartate receptors (NMDARs), contributing to EA-mediated analgesia. This highlights the crucial role of the endocannabinoid system in anterior cingulate cortex  for acupuncture analgesia, offering insights into its central mechanism.

Wu J, Hua L, Liu W, Yang X, Tang X, Yuan S, Zhou S, Ye Q, Cui S, Wu Z, Lai L, Tang C, Wang L, Yi W, Yao L, Xu N. Electroacupuncture Exerts Analgesic Effects by Restoring Hyperactivity via Cannabinoid Type 1 Receptors in the Anterior Cingulate Cortex in Chronic Inflammatory Pain. Mol Neurobiol. 2024 May;61(5):2949-2963. doi: 10.1007/s12035-023-03760-7. Epub 2023 Nov 13. PMID: 37957422; PMCID: PMC11043129.

Abstract

As one of the commonly used therapies for pain-related diseases in clinical practice, electroacupuncture (EA) has been proven to be effective. In chronic pain, neurons in the anterior cingulate cortex (ACC) have been reported to be hyperactive, while the mechanism by which cannabinoid type 1 receptors (CB1Rs) in the ACC are involved in EA-mediated analgesic mechanisms remains to be elucidated. In this study, we investigated the potential central mechanism of EA analgesia. A combination of techniques was used to detect the expression and function of CB1R, including quantitative real-time PCR (q-PCR), western blot (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and in vivo multichannel optical fibre recording, and neuronal activity was examined by in vivo two-photon imaging and in vivo electrophysiological recording. We found that the hyperactivity of pyramidal neurons in the ACC during chronic inflammatory pain is associated with impairment of the endocannabinoid system. EA at the Zusanli acupoint (ST36) can reduce the hyperactivity of pyramidal neurons and exert analgesic effects by increasing the endocannabinoid ligands anandamide (AEA), 2-arachidonoylglycerol (2-AG) and CB1R. More importantly, CB1R in the ACC is one of the necessary conditions for the EA-mediated analgesia effect, which may be related to the negative regulation of the N-methyl-D-aspartate receptor (NMDAR) by the activation of CB1R downregulating NR1 subunits of NMDAR (NR1) via histidine triad nucleotide-binding protein 1 (HINT1). Our study suggested that the endocannabinoid system in the ACC plays an important role in acupuncture analgesia and provides evidence for a central mechanism of EA-mediated analgesia.

Keywords: Analgesia; Anterior cingulate cortex; Cannabinoid type 1 receptor; Electroacupuncture; Inflammatory pain.