针对膝骨关节炎的 TRPV1 疼痛通路。

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Therapeutic Targets Pub Date : 2024-10-01 Epub Date: 2024-10-25 DOI:10.1080/14728222.2024.2416961
Ali Mobasheri, François Rannou, Stefan Ivanavicius, Philip G Conaghan
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引用次数: 0

摘要

简介:膝关节骨性关节炎(KOA)的发病率越来越高,但却缺乏有效的止痛疗法,因此对新型止痛疗法的大量需求尚未得到满足。瞬时受体电位类香草素 1(TRPV1)受体在痛觉神经元亚群中表达,在疼痛传递和调节中发挥着重要作用。在膝关节结构中,痛觉感受器大量存在:膝关节中表达 TRPV1 的痛觉感受器是调节 KOA 疼痛通路源头活动的合理靶点,可避免现有镇痛药的全身副作用。TRPV1 拮抗剂可诱导镇痛,但高热和热麻醉副作用限制了其应用。与 TRPV1 拮抗剂相比,用于镇痛的 TRPV1 激动剂的临床开发进展更快。辣椒素和树脂铁氧体毒素为调节 KOA 中 TRPV1 的活性提供了概念验证:关节内给药 TRPV1 激动剂可直接到达膝关节的靶神经末梢,为治疗 KOA 相关疼痛提供了一种潜在的变革性方法。在此,我们探讨了在了解 KOA 中膝关节神经支配、TRPV1 表达神经元的作用以及开发用于 KOA 的 TRPV1 调节剂方面取得的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting the TRPV1 pain pathway in osteoarthritis of the knee.

Introduction: The growing prevalence and lack of effective pain therapies for knee osteoarthritis (KOA) results in a substantial unmet need for novel analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed in subsets of nociceptive sensory neurons and has major roles in pain transmission and regulation. In the structures of the knee joint, nociceptors are present in abundance.

Areas covered: TRPV1-expressing nociceptors in the knee represent a rational target to modulate activity at the origin of the pain pathway in KOA and may avoid systemic side effects seen with currently available analgesics. TRPV1 antagonists can induce analgesia, but hyperthermia and thermal hypesthesia side effects have limited their utility. Clinical development of TRPV1 agonists for pain management has progressed further than that of TRPV1 antagonists. Capsaicin and resiniferatoxin have provided proof-of-concept for the modulation of TRPV1 activity in KOA.

Expert opinion: Intra-articular administration of TRPV1 agonists enables direct delivery to target nerve terminals in the knee, offering a potentially transformative approach for the management of pain associated with KOA. Here, we explore the advances in understanding innervation of the knee joint in KOA, the role of TRPV1-expressing neurons and progress in developing TRPV1 modulators for KOA.

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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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