PDF(Pubmed)
Abstract：
Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered that intrathecal IL-1 receptor antagonist reverses established pain in both sexes, and increased gene expression of inflammasome NLRP3 is specific to microglia and astrocytes rather than neurons, while IL-1beta is specific to microglia in both sexes. We report several sex differences in the expression level of the genes coding for IL-1beta, as well as the four inflammasomes responsible for IL-1beta release: NLRP3, AIM2, NLRP1, and NLRC4 in the spinal cord. Total mRNA, but not protein expression of IL-1beta is greater in females than males after CCI. Also, while CCI increases all four inflammasomes in both sexes, there are sex differences in relative levels of inflammasome expression. NLRP3 and AIM2 are more highly expressed in females, whereas NLRP1 expression is greater in males.
摘要：
女性代表大多数慢性疼痛患者,并且在人类慢性疼痛患者群体以及神经性疼痛的动物模型中显示更大的炎性免疫应答。慢性疼痛研究的最新发现揭示了炎症信号的性别差异，慢性神经性疼痛的感觉病理学的关键组成部分，邀请更多研究这些性别差异的细微差别。在这里，我们使用慢性压迫性损伤（CCI）模型来探索炎症细胞因子IL-1β在腰椎脊髓中表达和产生的异同。以及它在慢性疼痛中的作用。我们发现鞘内注射IL-1受体拮抗剂可以逆转两性的疼痛，和增加的基因表达的炎症小体NLRP3是特异性的小胶质细胞和星形胶质细胞，而不是神经元，而IL-1β对两性小胶质细胞具有特异性。我们报告了编码IL-1β的基因表达水平的几种性别差异，以及负责IL-1β释放的四种炎性体：脊髓中的NLRP3，AIM2，NLRP1和NLRC4。总mRNA，但在CCI后，女性的IL-1β蛋白表达不高于男性。此外，虽然CCI增加了两性的所有四种炎性体，炎症小体表达的相对水平存在性别差异。NLRP3和AIM2在女性中高表达，而NLRP1表达在男性中更高。
