Gut inflammation or injury causes intestinal hypersensitivity (IHS) and hyperalgesia, which can persist after the initiating pathology resolves, are often referred to somatic regions and exacerbated by psychological stress, anxiety or depression, suggesting the involvement of both the spinal cord and the brain. The supraspinal mechanisms of IHS remain to be fully elucidated, however, over the last decades the series of intestinal pathology-associated neuroplastic changes in the brain has been revealed, being potentially responsible for the phenomenon. This paper reviews current clinical and experimental data, including the authors’ own findings, on these functional, structural, and neurochemical/molecular changes within cortical, subcortical and brainstem regions processing and modulating sensory signals from the gut. As concluded in the review, IHS can develop and maintain due to the bowel inflammation/injury-induced persistent hyperexcitability of viscerosensory brainstem and thalamic nuclei and sensitization of hypothalamic, amygdala, hippocampal, anterior insular, and anterior cingulate cortical areas implicated in the neuroendocrine, emotional and cognitive modulation of visceral sensation and pain. An additional contribution may come from the pathology-triggered dysfunction of the brainstem structures inhibiting nociception. The mechanism underlying IHS-associated regional hyperexcitability is enhanced NMDA-, AMPA- and group I metabotropic receptor-mediated glutamatergic neurotransmission in association with altered neuropeptide Y, corticotropin-releasing factor, and cannabinoid 1 receptor signaling. These alterations are at least partially mediated by brain microglia and local production of cytokines, especially tumor necrosis factor α. Studying the IHS-related brain neuroplasticity in greater depth may enable the development of new therapeutic approaches against chronic abdominal pain in inflammatory bowel disease.

肠道炎症或损伤导致肠道超敏反应 (IHS) 和痛觉过敏，在初始病理消退后可能持续存在，通常涉及躯体区域，并因心理压力、焦虑或抑郁而加剧，表明脊髓和大脑均受累。IHS 的脊髓上机制仍有待充分阐明，然而，在过去的几十年中，已经揭示了大脑中一系列与肠道病理相关的神经可塑性变化，这可能是造成这种现象的原因。本文回顾了当前的临床和实验数据，包括作者自己的发现，这些数据涉及处理和调节来自肠道的感觉信号的皮质、皮质下和脑干区域内的这些功能、结构和神经化学/分子变化。正如审查中得出的结论，IHS 可以由于肠道炎症/损伤引起的内脏感觉脑干和丘脑核的持续过度兴奋以及下丘脑、杏仁核、海马、前岛叶和前扣带皮层区域的敏感性而发展和维持，这些区域与内脏神经内分泌、情绪和认知调节有关。感觉和疼痛。另一个贡献可能来自病理触发的脑干结构功能障碍抑制伤害感受。IHS 相关区域过度兴奋的潜在机制是增强 NMDA-、AMPA-和 I 组代谢型受体介导的谷氨酸能神经传递与改变的神经肽 Y、促肾上腺皮质激素释放因子和大麻素 1 受体信号传导相关。这些改变至少部分由脑小胶质细胞和细胞因子的局部产生介导，尤其是肿瘤坏死因子α。更深入地研究 IHS 相关的脑神经可塑性可能有助于开发针对炎症性肠病慢性腹痛的新治疗方法。