Program in Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada; email:
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Annu Rev Pharmacol Toxicol. 2023 Jan 20;63:565-583. doi: 10.1146/annurev-pharmtox-051421-112259.
The study of chronic pain continues to generate ever-increasing numbers of publications, but safe and efficacious treatments for chronic pain remain elusive. Recognition of sex-specific mechanisms underlying chronic pain has resulted in a surge of studies that include both sexes. A predominant focus has been on identifying sex differences, yet many newly identified cellular mechanisms and alterations in gene expression are conserved between the sexes. Here we review sex differences and similarities in cellular and molecular signals that drive the generation and resolution of neuropathic pain. The mix of differences and similarities reflects degeneracy in peripheral and central signaling processes by which neurons, immune cells, and glia codependently drive pain hypersensitivity. Recent findings identifying critical signaling nodes foreshadow the development of rationally designed, broadly applicable analgesic strategies. However, the paucity of effective, safe pain treatments compels targeted therapies as well to increase therapeutic options that help reduce the global burden of suffering.
慢性疼痛的研究不断产生越来越多的出版物，但安全有效的慢性疼痛治疗方法仍然难以捉摸。对慢性疼痛潜在机制的性别特异性认识导致了大量同时包括男性和女性的研究。主要重点是确定性别差异，但许多新确定的细胞机制和基因表达的改变在性别之间是保守的。在这里，我们回顾了驱动神经病理性疼痛产生和缓解的细胞和分子信号的性别差异和相似性。这种差异和相似性的混合反映了神经元、免疫细胞和神经胶质细胞共同驱动痛觉过敏的外周和中枢信号过程中的简并性。最近发现的关键信号节点预示着合理设计的、广泛适用的镇痛策略的发展。然而，有效、安全的疼痛治疗方法的缺乏迫使靶向治疗也增加治疗选择，以帮助减轻全球痛苦负担。
