The Endocannabinoid System Contributes to Electroacupuncture Analgesia.

Iona J. MacDonald,Yi-Hung Chen

doi:10.3389/fnins.2020.594219

Iona J. MacDonald, Yi-Hung Chen

Open Access

https://doi.org/10.3389/fnins.2020.594219

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Abstract

The extensive involvement of the endocannabinoid system (ECS) in vital physiological and cognitive processes of the human body has inspired many investigations into the role of the ECS and drugs, and therapies that target this system and its receptors. Activation of cannabinoid receptors 1 and 2 (CB1 and CB2) by cannabinoid treatments, including synthetic cannabinoids, alleviates behavioral responses to inflammatory and neuropathic pain. An increasing body of scientific evidence details how electroacupuncture (EA) treatments achieve effective analgesia and reduce inflammation by modulating cannabinoid signaling, without the adverse effects resulting from synthetic cannabinoid administration. CB1 receptors in the ventrolateral area of the periaqueductal gray are critically important for the mechanisms of the EA antinociceptive effect, while peripheral CB2 receptors are related to the anti-inflammatory effects of EA. This review explores the evidence detailing the endocannabinoid mechanisms involved in EA antinociception.

Highlights

Since its discovery in the 1990s, the complex signaling network of the endocannabinoid system (ECS) has increasingly been seen to be a key player in the regulation of numerous vital physiological and cognitive processes, such as female reproductive events, pain sensation, mood, and in mediating the pharmacological effects of cannabis (Wang et al, 2006; McPartland et al, 2007; Aizpurua-Olaizola et al, 2017; Toth et al, 2019).The ECS contains two major G-protein-coupled type 1 (CB1) and type 2 (CB2) cannabinoid receptors that are activated by the psychoactive ingredient of cannabis, 9-tetrahydrocannabinol (THC)
The main basic mechanisms triggered by CB1 and CB2 receptors are mediated by G proteins that are mostly of the Gi/o type, resulting in inhibition of activity of adenylate cyclases, the cAMP cascade and voltage-gated calcium (Ca2+) channels, and stimulation of mitogen-activated protein kinase (MAPK) activity (Di Marzo and Petrocellis, 2006)
EA-PC6-induced analgesia was reduced by intravlPAG inhibition of 2-AG synthesis, implicating a cannabinoid (2-AG)-dependent mechanism, which was supported by the finding that EA-PC6-induced antinociception was markedly attenuated in Cnr1−/− mice, which lack the CB1 receptor (Chen et al, 2018). These findings suggest that PC6-targeting low-frequency median nerve stimulation (MNS) activates hypothalamic orexin neurons, releasing orexins that activate postsynaptic OX1Rs in the ventrolateral area of the PAG (vlPAG) to generate 2-AG, which inhibits GABA release through CB1 receptors in the vlPAG and induces analgesia by disinhibiting vlPAG outputs (Chen et al, 2018)

Summary

Introduction

Since its discovery in the 1990s, the complex signaling network of the endocannabinoid system (ECS) has increasingly been seen to be a key player in the regulation of numerous vital physiological and cognitive processes, such as female reproductive events, pain sensation, mood, and in mediating the pharmacological effects of cannabis (Wang et al, 2006; McPartland et al, 2007; Aizpurua-Olaizola et al, 2017; Toth et al, 2019).The ECS contains two major G-protein-coupled type 1 (CB1) and type 2 (CB2) cannabinoid receptors that are activated by the psychoactive ingredient of cannabis, 9-tetrahydrocannabinol (THC). Subsequent research using murine pain models has demonstrated how low-frequency median nerve stimulation (MNS) using acupuncture needles at the PC6 acupoint (EAPC6) induces analgesia involving both CB1 receptors and OX1Rs (Chen et al, 2018).

Results

Conclusion