P2X receptors and modulation of pain transmission: Focus on effects of drugs and compounds used in traditional Chinese medicine

Abstract

Adenosine triphosphate (ATP) is thought to play an important role in nociceptive transmission or pain signals. ATP is implicated in peripheral pain signaling by acting on P2X receptors. ATP can act on cell bodies of primary afferent fibers. Opening of P2X receptor channels and subsequent membrane depolarization are generally regarded as a key element for extracellular ATP to produce pain. Nociceptive neurons express homomeric P2X 3 as well as heteromeric P2X 2/3 receptors. Both types of channels can be expressed separately or together in individual neuron. Selective antagonists for P2X 3 and/or P2X 2/3 receptors may represent a novel series of useful analgesic drugs. In addition to P2X 3 and P2X 2/3 receptors, other subtypes of the P2X receptor family are also involved in the modulation of nocicpetive transmission (e.g. P2X 4, P2X 7 receptors). Chinese traditional medicine, i.e., tetramethylpyrazine (TMP), sodium ferulate (SF) and puerarin can antagonize the nociceptive or pain transmission mediated by P2X 3 and/or P2X 2/3 receptors in primary afferent neurons. P2X 3 and/or P2X 2/3 receptors are the pharmacological targets of TMP, SF and puerarin for the therapeutic treatment of pain. The myocardial ischemic injury enhanced the sensitization of sympathetic afferent neurons with increased intensity of P2X 3, P2X 2/3 immunoreactivity, protein and mRNA expression in SCG, SG or NG neurons. P2X 3, P2X 2/3 receptors antagonist A-317491 inhibited the transmission of cardiac nociceptive response. Myocardial ischemic nociceptive signaling via P2X 3 and P2X 2/3 receptors in the transmission of rat SCG, SG, NG neuronal circuits induces the sympathoexcitatory reflex to exaggerate myocardial tissue injury. Blocking the nociceptive transmission of SCG, SG, NG neuronal circuits mediated by P2X 3 and P2X 2/3 receptors may improve the cardiac dysfunction. P2X 3 and P2X 2/3 receptors in SCG, SG, NG neurons could be considered as new targets for treating myocardial ischemic injury and cardiac arrhythmia.