Peripheral Receptors and Neuromediators Involved in the Antihyperalgesic Effects of Acupuncture: a State-of-the-art Review

The present study aims to describe state-of-the-art of preclinical studies that have investigated peripheral receptors and neuromediators involved in the antihyperalgesic effects of acupuncture. The PubMed, Scopus, and Web of Science databases were searched using the integrative review method. Preclinical articles that involved the study of peripheral receptors and neuromediators on the pain control effects of acupuncture in rats or mice were selected using a predefined search strategy. From this search, 456 articles were found, and 29 of them met the inclusion criteria of the study. The selected articles addressed the following peripheral receptors: opioid (n = 9), adenosine (n = 5), cannabinoid (n = 5), transient receptor potential vanilloid (TRPV) (n = 3), histamine (n = 2), adrenergic (n = 1), muscarinic (n = 1), corticotrophin-releasing factor (CRF) (n = 2), IL-1 (n = 1), and endothelin (n = 1) receptors. The peripheral neuromediators correlated with the peripheral pain control effect were as follows: opioid peptides (n = 4), adenosine (n = 3), histamine (n = 1), substance P (n = 1) calcitonin gene-related peptide (CGRP) (n = 1), anandamide (n = 1), nitric oxide (n = 1), and norepinephrine (n = 1). This review summarizes the methods used to investigate the peripheral effects of acupuncture and discusses the main findings on each family of receptors and neuromediators. Ten families of peripheral receptors and 8 types of neuromediators were correlated with the antihyperalgesic effects of acupuncture in preclinical studies. Considering the benefits of a better understanding of the role of peripheral receptors and neuromediators in the context pain management, the findings of the present study highlight the importance of deepening the exploration of the peripheral mechanisms of acupuncture.