神经性疼痛,几种疾病的常见症状,在世界范围内施加了巨大的社会经济负担。瞬时受体电位香草素1(TRPV1),非选择性阳离子通道主要表达在伤害性神经元,在伤害性感受中起着举足轻重的作用,通过检测各种内源性和外源性刺激,包括热量,促炎介质,和物理压力。TRPV1信号传导的失调进一步有助于神经性疼痛的病理生理学。因此,靶向TRPV1是开发具有改善疗效和安全性的新型镇痛药的有前景的策略.几种调节TRPV1活性的药理学方法,包括激动剂,拮抗剂,和生物TRPV1RNA干扰(RNAi,小干扰RNA[siRNA])已被探索。尽管临床前取得了成功,TRPV1靶向疗法的临床转化遇到了挑战,包括热疗,体温过低,辛辣,和脱敏。然而,正在进行的研究工作旨在通过结构修改来完善针对TRPV1的干预措施,选择性调节剂的发展,自然的发现,基于肽的候选药物。在这里,我们通过回顾现有文献并重点介绍当前研究活动,为参与研发专门针对TRPV1的新干预措施的研究者和临床医生提供指导.本研究进一步讨论了提高疗效的潜在未来研究努力,安全,和TRPV1候选物的耐受性,从而促进将这些发现转化为有效的临床干预措施,以缓解神经性疼痛疾病。
Neuropathic pain, a common symptom of several disorders, exerts a substantial socioeconomic burden worldwide. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel predominantly ex-pressed in nociceptive neurons, plays a pivotal role in nociception, by detecting various endogenous and exogenous stimuli, including heat, pro-inflammatory mediators, and physical stressors. Dysregulation of TRPV1 signaling further contributes to the pathophysiology of neuropathic pain. Therefore, targeting TRPV1 is a promising strategy for developing novel analgesics with improved efficacy and safety profiles. Several pharmacological approaches to modulate TRPV1 activity, including
agonists, antagonists, and biological TRPV1 RNA interference (RNAi, small interfering RNA [siRNA]) have been explored. Despite preclinical success, the clinical translation of TRPV1-targeted therapies has encountered challenges, including hyperthermia, hypothermia, pungency, and desensitization. Nevertheless, ongoing research efforts aim to refine TRPV1-targeted interventions through structural modifications, development of selective modulators, and discovery of natural, peptide-based drug candidates. Herein, we provide guidance for researchers and clinicians involved in the development of new interventions specifically targeting TRPV1 by reviewing the existing literature and highlighting current research activities. This study further discusses potential future research endeavors for enhancing the efficacy, safety, and tolerability of TRPV1 candidates, and thereby facilitates the translation of these discoveries into effective clinical interventions to alleviate neuropathic pain disorders.