Szabo-Pardi Thomas A, Syed Umar M, Castillo Zachary W, Burton Michael D
Neuroimmunology and Behavior Laboratory, Department of Neuroscience, Center for Advanced Pain Studies (CAPS), School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States.
Front Cell Dev Biol. 2021 Feb 18;9:624201. doi: 10.3389/fcell.2021.624201. eCollection 2021.
Peripheral nerve injury induces a myriad of immune-derived symptoms that negatively impacts pain, depression, and overall quality of life. Neuroimmune differences underlie sexual dimorphisms in various pain states. The innate immune system is a source of these sex differences, which promotes inflammation and pro-nociception through bidirectional signaling with the nervous system. Spatiotemporal interactions between leukocytes and sensory neurons could hold the key to explain ascribed differences between sexes. To date, studies have found it difficult to display these interactions. We are poised to answer important questions regarding the recruitment of peripheral leukocytes to key tissues of the pain system, the dorsal root ganglia (DRG) and sciatic nerve after nerve injury. We optically clear whole DRGs and sciatic nerves and concomitantly use multi-photon microscopy and transgenic reporter lines, to visualize leukocyte dynamics involved in neuropathic pain development following nerve injury. We observed robust sexual dimorphisms in leukocyte recruitment to the lumbar DRGs after nerve injury. We also assessed immune cell size and morphology to understand activation states in the context of nervous tissue inflammation. The altered mechanisms by which the male and female immune systems respond to nerve injury are still topics of further research, however; the continued use of next-generation imaging with advanced whole tissue image analysis remains an important tool in understanding the reciprocal interactions between neuronal and non-neuronal cells.
周围神经损伤会引发一系列源自免疫的症状，对疼痛、抑郁和整体生活质量产生负面影响。神经免疫差异是各种疼痛状态下性别差异的基础。先天性免疫系统是这些性别差异的一个来源，它通过与神经系统的双向信号传导促进炎症和伤害感受。白细胞与感觉神经元之间的时空相互作用可能是解释两性之间既定差异的关键。迄今为止，研究发现难以展示这些相互作用。我们准备回答有关神经损伤后外周白细胞募集到疼痛系统的关键组织——背根神经节（DRG）和坐骨神经的重要问题。我们对整个DRG和坐骨神经进行光学透明处理，并同时使用多光子显微镜和转基因报告系，以可视化神经损伤后参与神经性疼痛发展的白细胞动态。我们观察到神经损伤后白细胞募集到腰段DRG存在明显的性别差异。我们还评估了免疫细胞的大小和形态，以了解神经组织炎症背景下的激活状态。然而，男性和女性免疫系统对神经损伤作出反应的改变机制仍是进一步研究的课题；继续使用具有先进全组织图像分析功能的下一代成像技术仍然是理解神经元和非神经元细胞之间相互作用的重要工具。
