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

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 P2X3 as well as heteromeric P2X2/3 receptors. Both types of channels can be expressed separately or together in individual neuron. Selective antagonists for P2X3 and/or P2X2/3 receptors may represent a novel series of useful analgesic drugs. In addition to P2X3 and P2X2/3 receptors, other subtypes of the P2X receptor family are also involved in the modulation of nocicpetive transmission (e.g. P2X4, P2X7 receptors). Chinese traditional medicine, i.e., tetramethylpyrazine (TMP), sodium ferulate (SF) and puerarin can antagonize the nociceptive or pain transmission mediated by P2X3 and/or P2X2/3 receptors in primary afferent neurons. P2X3 and/or P2X2/3 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 P2X3, P2X2/3 immunoreactivity, protein and mRNA expression in SCG, SG or NG neurons. P2X3, P2X2/3 receptors antagonist A-317491 inhibited the transmission of cardiac nociceptive response. Myocardial ischemic nociceptive signaling via P2X3 and P2X2/3 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 P2X3 and P2X2/3 receptors may improve the cardiac dysfunction. P2X3 and P2X2/3 receptors in SCG, SG, NG neurons could be considered as new targets for treating myocardial ischemic injury and cardiac arrhythmia.

Research highlights▶ P2X receptors are involved in pain transmission. ▶ Selective antagonists for P2X3 and/or P2X2/3, P2X4, P2X7 receptors represent a novel series of useful analgesic drugs. ▶ Chinese traditional medicine can antagonize the nociceptive or pain transmission mediated by P2X3 and/or P2X2/3 receptors; P2X3 and P2X2/3 receptors in SCG, SG, NG neurons could be considered as new targets for treating myocardial ischemic injury and cardiac arrhythmia.