Smith Angela F, Plumb Ashley N, Berardi Giovanni, Sluka Kathleen A
Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa, USA.
Department of Neuroscience, University of Texas at Dallas, Richardson, Texas, USA.
J Clin Invest. 2025 Jun 2;135(11). doi: 10.1172/JCI191931.
Chronic pain affects more than 50 million Americans, with women disproportionately affected by severe pain, pain interference, and overall disability. The development of chronic pain is multifactorial and often begins with an incident of acute pain associated with an injury or a surgical procedure that transitions to persistent pain lasting for months or years. Despite this, there are limited clinical studies investigating sex differences in predictors and biomarkers for the transition to chronic pain. Several preclinical animal models have been developed to gain a better understanding of the mechanisms for the transition to chronic pain, and several sex-specific mechanisms have been identified across multiple systems. These preclinical models generally involve a multiple-insult approach, in which a priming insult enhances sensitivity to a subsequent induction stimulus. There is emerging evidence from preclinical research for several male-specific and female-specific mechanisms, as well as several studies showing shared mechanisms. Here, we review the clinical and preclinical literature covering sex differences in the periphery and immune system, the central nervous system, and the endocrine system related to the transition to chronic pain. We further highlight gaps in the literature and provide recommendations for future research to understand sex-specific differences in the transition to chronic pain.
慢性疼痛影响着超过5000万美国人，女性在严重疼痛、疼痛干扰及整体残疾方面受到的影响尤为严重。慢性疼痛的形成是多因素的，通常始于与损伤或外科手术相关的急性疼痛事件，而后转变为持续数月或数年的持续性疼痛。尽管如此，针对慢性疼痛转变过程中预测因素和生物标志物的性别差异进行的临床研究却很有限。为了更好地理解慢性疼痛转变的机制，已经开发了几种临床前动物模型，并且在多个系统中发现了几种性别特异性机制。这些临床前模型通常采用多重损伤方法，即初次损伤会增强对后续诱导刺激的敏感性。临床前研究中出现了一些关于男性特异性和女性特异性机制的证据，也有几项研究表明存在共同机制。在此，我们综述了临床和临床前文献，内容涉及外周和免疫系统、中枢神经系统以及内分泌系统中与慢性疼痛转变相关的性别差异。我们进一步强调了文献中的空白，并为未来研究提供建议，以了解慢性疼痛转变中的性别特异性差异。
