An update on targets for treating osteoarthritis pain: NGF and TRPV1.

Alia M Obeidat, Anita Donner, Rachel E Miller
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引用次数: 6

Abstract

Purpose of review: a)Osteoarthritis (OA) is the most common form of arthritis, and pain is the primary symptom of the disease, yet analgesic options for treating OA pain remain limited. In this review, we aimed to give an update on the current clinical and preclinical studies targeting two pathways that are being investigated for treating OA pain: the nerve growth factor (NGF) pathway and the transient receptor potential vanilloid-1 (TRPV1) pathway.

Recent findings: b)Antibodies against NGF, small molecule inhibitors of TrkA, TRPV1 agonists, and TRPV1 antagonists are all in different stages of clinical and pre-clinical testing for the treatment of OA pain. NGF antibodies have shown efficacy in the primary endpoints tested compared to placebo, however, rapidly progressive OA has been consistently observed in a subset of patients and the cause remains unclear. TRPV1 agonists have also demonstrated reduced pain with no serious adverse events - the most common adverse events include a burning or warming sensation upon administration.

Summary: c)Targeting the NGF and TRPV1 pathways appear effective for reducing OA pain, but further work is needed to better understand which patients may benefit most from these treatments. The anti-NGF antibody tanezumab and the TRPV1 agonist CNTX-4975 have both received fast-track designation from the FDA for the treatment of OA pain.

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治疗骨关节炎疼痛靶点的最新进展:NGF和TRPV1。
综述目的:a)骨关节炎(OA)是最常见的关节炎形式,疼痛是该疾病的主要症状,然而治疗OA疼痛的镇痛选择仍然有限。在这篇综述中,我们的目的是提供当前临床和临床前研究的最新进展,这些研究针对两种正在研究的治疗OA疼痛的途径:神经生长因子(NGF)途径和瞬时受体电位香草素-1 (TRPV1)途径。近期发现:b)抗NGF抗体、TrkA小分子抑制剂、TRPV1激动剂和TRPV1拮抗剂治疗OA疼痛均处于临床和临床前试验的不同阶段。与安慰剂相比,NGF抗体在主要终点测试中显示出疗效,然而,在一部分患者中一直观察到快速进展的OA,其原因尚不清楚。TRPV1激动剂也显示减轻疼痛,无严重不良事件-最常见的不良事件包括给药后灼烧感或热感。总结:c)靶向NGF和TRPV1通路似乎对减轻OA疼痛有效,但需要进一步的工作来更好地了解哪些患者可能从这些治疗中获益最多。抗ngf抗体tanezumab和TRPV1激动剂CNTX-4975都获得了FDA的快速通道指定,用于治疗OA疼痛。
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