Departments of Pharmacology and.
Psychiatry (NRU), University of Alberta, Edmonton, AB, Canada.
Pain. 2019 May;160(5):1037-1049. doi: 10.1097/j.pain.0000000000001483.
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease with many known structural and functional changes in the central nervous system. A well-recognized, but poorly understood, complication of MS is chronic pain. Little is known regarding the influence of sex on the development and maintenance of MS-related pain. This is important to consider, as MS is a predominantly female disease. Using the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we demonstrate sex differences in measures of spinal cord inflammation and plasticity that accompany tactile hypersensitivity. Although we observed substantial inflammatory activity in both sexes, only male EAE mice exhibit robust staining of axonal injury markers and increased dendritic arborisation in morphology of deep dorsal horn neurons. We propose that tactile hypersensitivity in female EAE mice may be more immune-driven, whereas pain in male mice with EAE may rely more heavily on neurodegenerative and plasticity-related mechanisms. Morphological and inflammatory differences in the spinal cord associated with pain early in EAE progression supports the idea of differentially regulated pain pathways between the sexes. Results from this study may indicate future sex-specific targets that are worth investigating for their functional role in pain circuitry.
多发性硬化症（MS）是一种神经退行性自身免疫性疾病，中枢神经系统有许多已知的结构和功能变化。MS 的一个公认但知之甚少的并发症是慢性疼痛。关于性别对 MS 相关疼痛的发展和维持的影响知之甚少。这一点很重要，因为 MS 主要发生在女性身上。本研究使用实验性自身免疫性脑脊髓炎（EAE）MS 小鼠模型，证明了与触觉过敏相关的脊髓炎症和可塑性测量中的性别差异。尽管我们在两性中均观察到大量的炎症活性，但只有雄性 EAE 小鼠表现出明显的轴突损伤标志物染色和深部背角神经元树突分支的增加。我们提出，雌性 EAE 小鼠的触觉过敏可能更多地由免疫驱动，而患有 EAE 的雄性小鼠的疼痛可能更多地依赖于神经退行性和可塑性相关机制。EAE 早期进展中与疼痛相关的脊髓形态和炎症差异支持性别之间疼痛通路差异调节的观点。本研究的结果可能表明，未来值得研究性别特异性靶点，以了解其在疼痛回路中的功能作用。
