Supraspinal Mechanisms of Intestinal Hypersensitivity
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REVIEW PAPER
Supraspinal Mechanisms of Intestinal Hypersensitivity Olga A. Lyubashina1 · Ivan B. Sivachenko1 · Sergey S. Panteleev1 Received: 5 June 2020 / Accepted: 22 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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, corticotropinreleasing 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. Keywords Intestinal hypersensitivity · Bowel inflammation · Brain neuroplasticity · Central sensitization · Abdominal pain
Introduction Healthy individuals do not consciously perceive most of signals emanating from their viscera. However, patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) commonly possess enhanced perception of physiological stimuli in the gut (Andersson et al. 2003; Ludidi et al. 2012; Raffals and Camilleri 2013; Simrén et al. 2018). The heightened sensation, termed visceral or intestinal hypersensitivity (IHS), is currently considered to play a major etiological role in chronic abdominal pain – the main cause of disability and healthcare seeking in both organic * Olga A. Lyubashina [email protected] 1
Laboratory of Cortico‑Visceral Physiology, Pavlov Institute of Physiology
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