De Logu Francesco, Geppetti Pierangelo
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.
Handb Exp Pharmacol. 2019;260:161-186. doi: 10.1007/164_2019_336.
A large series of different ion channels have been identified and investigated as potential targets for new medicines for the treatment of a variety of human diseases, including pain. Among these channels, the voltage gated calcium channels (VGCC) are inhibited by drugs for the treatment of migraine, neuropathic pain or intractable pain. Transient receptor potential (TRP) channels are emerging as important pain transducers as they sense low pH media or oxidative stress and other mediators and are abundantly found at sites of inflammation or tissue injury. Low pH may also activate acid sensing ion channels (ASIC) and mechanical forces stimulate the PIEZO channels. While potent agonists of TRP channels due to their desensitizing action on pain transmission are used as topical applications, the potential of TRP antagonists as pain therapeutics remains an exciting field of investigation. The study of ASIC or PIEZO channels in pain signaling is in an early stage, whereas antagonism of the purinergic P2X channels has been reported to provide beneficial effects in chronic intractable cough. The present chapter covers these intriguing channels in great detail, highlighting their diverse mechanisms and broad potential for therapeutic utility.
大量不同的离子通道已被识别和研究，作为治疗包括疼痛在内的多种人类疾病的新药潜在靶点。在这些通道中，电压门控钙通道（VGCC）可被用于治疗偏头痛、神经性疼痛或顽固性疼痛的药物所抑制。瞬时受体电位（TRP）通道正成为重要的疼痛传导器，因为它们能感知低pH介质或氧化应激及其他介质，且在炎症或组织损伤部位大量存在。低pH也可能激活酸敏感离子通道（ASIC），机械力会刺激压电通道（PIEZO）。虽然由于TRP通道对疼痛传递的脱敏作用，其强效激动剂被用作局部应用，但TRP拮抗剂作为疼痛治疗药物的潜力仍是一个令人兴奋的研究领域。对ASIC或PIEZO通道在疼痛信号传导中的研究尚处于早期阶段，而据报道，嘌呤能P2X通道的拮抗作用在慢性顽固性咳嗽中具有有益效果。本章详细介绍了这些有趣的通道，突出了它们多样的机制和广泛的治疗应用潜力。
