Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Pharmacol Ther. 2012 Feb;133(2):189-204. doi: 10.1016/j.pharmthera.2011.10.008. Epub 2011 Nov 15.
The necessity of safe and effective treatments for chronic pain has intensified the search for new analgesic drugs. In the last few years, members of a closely-related family of ion channels, called transient receptor potential (TRP) have been identified in different cell types and their functions in physiological and pathological conditions have been characterized. The transient receptor potential ankyrin 1 (TRPA1), originally called ANKTM1 (ankyrin-like with transmembrane domains protein 1), is a molecule that has been conserved in different species during evolution; TRPA1 is a cation channel that functions as a cellular sensor, detecting mechanical, chemical and thermal stimuli, being a component of neuronal, epithelial, blood and smooth muscle tissues. In mammals, TRPA1 is largely expressed in primary sensory neurons that mediate somatosensory processes and nociceptive transmission. Recent studies have described the role of TRPA1 in inflammatory and neuropathic pain. However, its participation in cold sensation has not been agreed in different studies. In this review, we focus on data that support the relevance of the activation and blockade of TRPA1 in pain transmission, as well as the mechanisms underlying its activation and modulation by exogenous and endogenous stimuli. We also discuss recent advances in the search for new analgesic medicines targeting the TRPA1 channel.
治疗慢性疼痛的安全有效的方法的必要性加剧了对新型镇痛药物的研究。在过去的几年中，被称为瞬时受体电位（TRP）的离子通道家族的密切相关成员已在不同的细胞类型中被鉴定出来，并且已经描述了它们在生理和病理条件下的功能。瞬时受体电位锚蛋白 1（TRPA1），最初称为 ANKTM1（具有跨膜结构域的锚蛋白样蛋白 1），是一种在进化过程中不同物种中保守的分子；TRPA1 是一种阳离子通道，作为细胞传感器发挥作用，检测机械、化学和热刺激，是神经元、上皮细胞、血液和平滑肌组织的组成部分。在哺乳动物中，TRPA1 主要表达在介导躯体感觉过程和伤害性传递的初级感觉神经元中。最近的研究描述了 TRPA1 在炎症性和神经性疼痛中的作用。然而，不同的研究并不认同 TRPA1 在冷觉中的参与。在这篇综述中，我们重点介绍支持 TRPA1 在疼痛传递中的激活和阻断相关性的数据，以及其被外源性和内源性刺激激活和调节的机制。我们还讨论了针对 TRPA1 通道寻找新型镇痛药物的最新进展。
