Current therapies for the treatment of chronic pain provide inadequate relief for millions of suffering patients, demonstrating the need for better therapies that will treat pain effectively and improve the quality of patient’s lives. Better understanding of the mechanisms that mediate chronic pain is critical for developing drugs with improved clinical outcomes. Adenosine triphosphate (ATP) is a key modulator in nociceptive pathways. Release of ATP from injured tissue or sympathetic efferents has sensitizing effects on sensory neurons in the periphery, and presynaptic vesicular release of ATP from the central terminals can increase glutamate release thereby potentiating downstream central sensitization mechanisms, a condition thought to underlie many chronic pain conditions. The purinergic receptors on sensory nerves primarily responsible for ATP signaling are P2X3 and P2X2/3. Selective knockdown experiments, or inhibition with small molecules, demonstrate P2X3-containing receptors are key targets to modulate nociceptive signals. Preclinical studies have identified that P2X3-containing receptors are critical for sensory transduction for bladder function, and clinical studies have shown promise in treatment for bladder pain and pain associated with osteoarthritis. Further clinical characterization of antagonists to P2X3-containing receptors may lead to improved therapies in the treatment of chronic pain.

目前治疗慢性疼痛的疗法无法充分缓解数百万痛苦的患者，这表明需要更好的疗法来有效治疗疼痛并改善患者的生活质量。更好地了解介导慢性疼痛的机制对于开发改善临床结果的药物至关重要。三磷酸腺苷 (ATP) 是伤害感受途径的关键调节剂。受损组织或交感传出神经释放的 ATP 对周围感觉神经元具有敏化作用，而中枢末端突触前囊泡释放的 ATP 可以增加谷氨酸释放，从而增强下游中枢敏化机制，这种情况被认为是许多慢性疼痛病症的基础。感觉神经上主要负责 ATP 信号传导的嘌呤能受体是 P2X3 和 P2X2/3。选择性敲除实验或小分子抑制表明，含有 P2X3 的受体是调节伤害性信号的关键靶标。临床前研究已发现，含有 P2X3 的受体对于膀胱功能的感觉转导至关重要，临床研究也显示出在治疗膀胱疼痛和骨关节炎相关疼痛方面的前景。含 P2X3 受体拮抗剂的进一步临床特征可能会改善慢性疼痛的治疗方法。