Spinal neuron-glia-immune interaction in cross-organ sensitization.
Spinal neuron-glia-immune interaction in cross-organ sensitization.
复制标题
DOI：
10.1152/ajpgi.00323.2020
复制
发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
L. Qiao;Namrata Tiwari
中科院分区：
文献类型：
--
作者：
L. Qiao;Namrata Tiwari
炎症性肠病(IBD)和肠易激综合征(IBS)历史上被认为是具有高结肠敏感性的区域性胃肠道疾病，越来越多的人认识到同时存在其他内脏和躯体器官的功能障碍，如膀胱多动、腿部疼痛和皮肤过敏。器官间感觉串扰通常被称为“跨器官敏化”。这些器官在解剖上相距甚远，通过将它们的感觉信息投射到背根神经节(DRG)，然后再投射到脊髓进行综合处理，在生理上相互关联。结肠传入神经元的敏化如何传递伤害性信息以激活支配远处器官的初级传入这一基本问题仍然是模糊的。在DRG中，初级传入神经元被卫星胶质细胞(SGCs)包围，巨噬细胞在损伤信号的作用下聚集，形成神经元-胶质-巨噬细胞三联体。星形胶质细胞和小胶质细胞是脊髓中主要的非神经细胞，在物理和化学上与感觉突触相互作用。到目前为止收集的累积证据表明，神经元、神经胶质细胞和免疫细胞之间的旁分泌/自分泌相互作用在感觉交叉激活中起着不可或缺的作用。在跨器官敏化的过程中，两分传入、脊髓感觉会聚、脊神经汇聚、初级传入中枢轴突的广泛萌发都有重要的作用，但它们的功能贡献还需要更多的结果来解释。位于血脑屏障外的DRG在跨器官敏化中位于感觉流级联的上游，可能是更安全的治疗靶点，产生的中枢性不良反应较少。
Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), historically considered as regional gastrointestinal disorders with heightened colonic sensitivity, are increasingly recognized to have concurrent dysfunction of other visceral and somatic organs, such as urinary bladder hyperactivity, leg pain, and skin hypersensitivity. The inter-organ sensory crosstalk is, at large, termed 'cross-organ sensitization'. These organs, anatomically distant from one another, physiologically interlock through projecting their sensory information into dorsal root ganglia (DRG) and then the spinal cord for integrative processing. The fundamental question of how sensitization of colonic afferent neurons conveys nociceptive information to activate primary afferents that innervate distant organs remains ambiguous. In DRG, primary afferent neurons are surrounded by satellite glial cells (SGCs) and macrophage accumulation in response to signals of injury to form neuron-glia-macrophage triad. Astrocytes and microglia are major resident non-neuronal cells in the spinal cord to interact, physically and chemically, with sensory synapses. Cumulative evidence gathered so far indicate the indispensable roles of paracrine/autocrine interactions among neurons, glial cells, and immune cells in sensory cross-activation. Dichotomizing afferents, sensory convergency in the spinal cord, spinal nerve comingling, and extensive sprouting of central axons of primary afferents each has significant roles in the process of cross-organ sensitization, however, more results are required to explain their functional contributions. DRG that are located outside the blood-brain-barrier and reside upstream in the cascade of sensory flow from one organ to the other in cross-organ sensitization could be safer therapeutic targets to produce less central adverse effects.