P2x3-receptor desensitization as an alternative mechanism of analgesia

One of the most important current medical problems is the synthesis of substances that could suppress pathological pain. It has not been yet invented any method for chronic pain inhibition. Chronic pain is largely mediated by the activation of purinergic P2X3- and P2X2/3-receptors. They are expressed in nociceptive sensory neurons and are the prospective targets for analgesic drugs. There are several potential strategies to prevent P2X3 receptor activation. Recent studies have shown that P2X3-receptor antagonists and genetic deletion may have analgesic effects in inflammatory and neuropathic models. P2X3-receptors have fast and persistent desensitization. By influencing this property it could serve to reduce the ATP-mediated sensation of chronic pain. Therefore, in this review we outline and analyze the effectiveness and prospects of pharmacological agents acting through desensitization of P2X3-receptor versus its competitive antagonists.