Musculoskeletal pain such as osteoarthritis (OA) and low back pain (LBP) are very common and contribute to enormous burden and societal costs, despite dramatic therapeutic advances over recent decades. Novel approaches and targeted therapies are required to satisfy the urgent unmet medical need of musculoskeletal pain relief in both conditions. Nerve growth factor (NGF) inhibitors have utilized novel mechanisms different from conventional drugs, which have a variety of gastrointestinal, cardiac, or renal adverse effects. Several phase 2/3 studies have been accomplished for these drugs, such as tanezumab, fasinumab, and tyrosine receptor kinase A (TrkA) inhibitors. We searched the literature using the PubMed database and clinical trials using ClinicalTrials.gov to identify original papers, meta-analyses as well as ongoing clinical trials assessing the efficacy and safety profile of these drugs. In this narrative review, we briefly overview the disease burden of musculoskeletal pain, the role of NGF signaling and its receptors in the genesis of pain, and the mechanisms of action of inhibitors of NGF signaling and downstream pathways, and then discuss the efficacy and safety of each investigational drug in OA and LBP. Finally, we briefly review two serious adverse effects of NGF inhibitors, namely rapidly progressive OA and sympathetic system effects, and conclude with possible barriers and potential research directions to overcome these.

尽管近几十年来治疗取得了显着进展，但骨关节炎 (OA) 和腰痛 (LBP) 等肌肉骨骼疼痛非常常见，并造成了巨大的负担和社会成本。需要新的方法和靶向治疗来满足在这两种情况下缓解肌肉骨骼疼痛的迫切未满足的医疗需求。神经生长因子 (NGF) 抑制剂利用了不同于传统药物的新机制，传统药物具有多种胃肠道、心脏或肾脏副作用。这些药物已完成多项 2/3 期研究，例如 tanezumab、fasinumab 和酪氨酸受体激酶 A (TrkA) 抑制剂。我们使用 PubMed 数据库和临床试验检索了文献，使用 ClinicalTrials.gov 来识别原始论文，荟萃分析以及正在进行的临床试验评估这些药物的有效性和安全性。在这篇叙述性综述中，我们简要概述了肌肉骨骼疼痛的疾病负担、NGF 信号传导及其受体在疼痛发生中的作用，以及 NGF 信号传导和下游通路抑制剂的作用机制，然后讨论了其有效性和安全性。 OA 和 LBP 中的每种研究药物。最后，我们简要回顾了 NGF 抑制剂的两个严重不良反应，即快速进展的 OA 和交感神经系统影响，并总结了可能存在的障碍和克服这些障碍的潜在研究方向。NGF 信号传导及其受体在疼痛发生中的作用，以及 NGF 信号传导和下游通路抑制剂的作用机制，然后讨论每种研究药物在 OA 和 LBP 中的有效性和安全性。最后，我们简要回顾了 NGF 抑制剂的两个严重不良反应，即快速进展的 OA 和交感神经系统影响，并总结了可能存在的障碍和克服这些障碍的潜在研究方向。NGF 信号传导及其受体在疼痛发生中的作用，以及 NGF 信号传导和下游通路抑制剂的作用机制，然后讨论每种研究药物在 OA 和 LBP 中的有效性和安全性。最后，我们简要回顾了 NGF 抑制剂的两个严重不良反应，即快速进展的 OA 和交感神经系统影响，并总结了可能存在的障碍和克服这些障碍的潜在研究方向。