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.

中文翻译：

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跨器官致敏中的脊髓神经元-胶质细胞-免疫相互作用

炎症性肠病 (IBD) 和肠易激综合征 (IBS) 历来被认为是具有高结肠敏感性的区域性胃肠道疾病，越来越多地认识到它们同时存在其他内脏和躯体器官的功能障碍，例如膀胱多动、腿部疼痛和皮肤超敏反应。器官间感觉串扰一般称为“跨器官致敏”。这些器官在解剖学上彼此相距甚远，通过将它们的感觉信息投射到背根神经节 (DRG) 中，然后投射到脊髓中进行整合处理，从而在生理上互锁。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神经的基本问题仍然不明确。在 DRG 中，初级传入神经元被卫星神经胶质细胞 (SGC) 和巨噬细胞聚集包围，以响应损伤信号形成神经元-神经胶质-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常驻非神经元细胞，它们与感觉突触进行物理和化学相互作用。迄今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。二分传入神经、脊髓中的感觉会聚、脊神经混合和初级传入神经中枢轴突的广泛萌发，均在跨器官致敏过程中具有重要作用，但是，需要更多的结果来解释它们的功能贡献。