Department of Health Sciences, Clinical Pharmacology Unit, University of Florence , Florence, Italy.
Expert Opin Ther Targets. 2020 Oct;24(10):997-1008. doi: 10.1080/14728222.2020.1815191. Epub 2020 Sep 11.
Chronic pain affects approximatively 30-50% of the population globally. Pathologies such as migraine, diabetic neuropathy, nerve injury and treatment with chemotherapeutic agents, can induce chronic pain. Members of the transient receptor potential (TRP) channels, including the TRP ankyrin 1 (TRPA1), have a major role in pain.
We focus on TRPA1 as a therapeutic target for pain relief. The structure, localization, and activation of the channel and its implication in different pathways to signal pain are described. This paper underlines the role of pharmacological interventions on TRPA1 to reduce pain in numerous pain conditions. We conducted a literature search in PubMed up to and including July 2020.
Our understanding of the molecular mechanisms underlying the sensitization of central and peripheral nociceptive pathways is limited. Preclinical evidence indicates that, in murine models of pain diseases, numerous mechanisms converge on the pathway that encompasses oxidative stress and Schwann cell TRPA1 to sustain chronic pain. Programs to identify and develop treatments to attenuate TRPA1-mediated chronic pain have emerged from this knowledge. Antagonists explored as a novel class of analgesics have a new and promising target in the TRPA1 expressed by peripheral glial cells.
慢性疼痛影响全球约 30-50%的人口。偏头痛、糖尿病性神经病、神经损伤和化疗药物治疗等疾病可引发慢性疼痛。瞬时受体电位 (TRP) 通道成员，包括 TRP 锚蛋白 1 (TRPA1)，在疼痛中起主要作用。
我们专注于 TRPA1 作为缓解疼痛的治疗靶点。本文描述了通道的结构、定位和激活及其在不同疼痛信号通路中的作用。本文强调了药理学干预 TRPA1 以减轻多种疼痛状况下疼痛的作用。我们在 PubMed 上进行了截至 2020 年 7 月的文献检索。
我们对中枢和外周伤害性通路敏化的分子机制的理解有限。临床前证据表明，在疼痛疾病的小鼠模型中，许多机制集中在包括氧化应激和施万细胞 TRPA1 在内的途径上，以维持慢性疼痛。从这些知识中出现了识别和开发治疗方法以减轻 TRPA1 介导的慢性疼痛的计划。作为一类新型镇痛药，探索的拮抗剂在外周神经胶质细胞表达的 TRPA1 中具有新的有前途的靶标。
