Boston University School of Medicine, Boston, MA.
Department of Anesthesiology, University of Chicago Medical Center, Chicago, IL.
Pain Physician. 2021 Mar;24(2):153-163.
Although conventional pain relief therapeutics have centered around mu-opioid agonists, these drugs are limited by adverse side effects, including respiratory depression and addiction potential. The ongoing opioid epidemic has galvanized research into novel analgesic therapies with more favorable profiles. New pharmacologic agents have been developed to target neuronal pathways involved in pain sensation. Certain receptors have been recognized to mediate nociceptive transmission, central sensitization, and the development of chronic pain states.
We conducted a literature review to identify potential targets for novel analgesic therapies.
This study is a narrative review of potential analgesic targets. We characterize their antinociceptive mechanisms of action and evaluate their therapeutic potential.
A systemized search of available literature on novel analgesics was performed. A search was performed through the PubMed database to identify articles with key words of "novel analgesics," "novel non-opioid analgesics," "novel pain targets," and "non-opioid analgesics." Potential drug classes were identified and researched through corresponding keywords, with an emphasis on publications from 2018 to 2020. Older articles were included if frequently referenced by current literature.
Potential novel analgesic targets include Nav1.7, Nav1.8, CaV2.2, and transient receptor potential vanilloid-1 (TRPV1) cation channel receptors in the peripheral nervous system. Other approaches disrupt the synthesis of pronociceptive signaling molecules such as nitric oxide, prostaglandin E2, and interleukin-6 (IL-6). Within central pain pathways, modification of kappa-opioid, delta-opioid, N-methyl-D-aspartate, and cannabinoid receptors have been investigated in chronic pain and hyperalgesia models. Recent advances in molecular technology have also presented opportunities to modify protein expression or the cellular genome altogether.
Several analgesic targets have only demonstrated efficacy in preclinical trials. There are limited data evaluating the long-term safety profiles of therapies further on in development.
We provide an overview of potential analgesic therapies in various stages of development, which may become clinically relevant in the near future. Some drugs such as TRPV1 agonists, anti-IL-6, and anti-nerve growth factor antibodies have demonstrated analgesic effect in specific clinical pain states.
尽管传统的止痛治疗方法主要集中在μ-阿片受体激动剂上，但这些药物存在不良反应，包括呼吸抑制和成瘾潜力。持续的阿片类药物流行促使人们研究具有更有利特征的新型镇痛疗法。已经开发出新型药物来针对参与疼痛感觉的神经元途径。某些受体已被认为介导伤害性传递、中枢敏化和慢性疼痛状态的发展。
我们进行了文献综述，以确定新型镇痛疗法的潜在靶点。
这是一篇关于潜在镇痛靶点的叙述性综述。我们描述了它们的镇痛作用机制，并评估了它们的治疗潜力。
对新型镇痛药的现有文献进行了系统检索。通过 PubMed 数据库搜索了关键词为“新型镇痛药”、“新型非阿片类镇痛药”、“新型疼痛靶点”和“非阿片类镇痛药”的文章。通过相应的关键词确定了潜在的药物类别，并进行了研究，重点关注 2018 年至 2020 年的出版物。如果当前文献经常引用较旧的文章，则将其包括在内。
潜在的新型镇痛药靶点包括外周神经系统中的 Nav1.7、Nav1.8、CaV2.2 和瞬时受体电位香草酸-1 (TRPV1) 阳离子通道受体。其他方法破坏了促伤害性信号分子如一氧化氮、前列腺素 E2 和白细胞介素-6 (IL-6) 的合成。在内源性疼痛途径中，κ-阿片受体、δ-阿片受体、N-甲基-D-天冬氨酸和大麻素受体的修饰已在慢性疼痛和痛觉过敏模型中进行了研究。分子技术的最新进展也为修饰蛋白质表达或整个细胞基因组提供了机会。
几种镇痛药靶点仅在临床前试验中显示出疗效。进一步开发的治疗方法的长期安全性数据有限。
我们提供了处于不同开发阶段的潜在镇痛疗法的概述，这些疗法在不久的将来可能具有临床相关性。一些药物，如 TRPV1 激动剂、抗 IL-6 和抗神经生长因子抗体，已在特定的临床疼痛状态中显示出镇痛作用。
