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Open AccessArticle

Deepening the Mechanisms of Visceral Pain Persistence: An Evaluation of the Gut-Spinal Cord Relationship

1
Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
2
Department of Experimental and Clinical Medicine—DMSC, Anatomy and Histology Section, University of Florence, L. go Brambilla 3, 50134 Florence, Italy
3
Department of Clinical and Experimental Medicine, Unit of Histology, University of Pisa, 56126 Pisa, Italy
4
Department of Pharmacy, Unit of Pharmacology, University of Pisa, 56126 Pisa, Italy
5
Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, 56126 Pisa, Italy
6
Interdepartmental Research Center “Nutraceuticals and Food for Health”, University of Pisa, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Cells 2020, 9(8), 1772; https://doi.org/10.3390/cells9081772
Received: 5 June 2020 / Revised: 11 July 2020 / Accepted: 20 July 2020 / Published: 24 July 2020
(This article belongs to the Special Issue Novel Insights into Molecular Mechanisms of Chronic Pain)
The management of visceral pain is a major clinical problem in patients affected by gastrointestinal disorders. The poor knowledge about pain chronicization mechanisms prompted us to study the functional and morphological alterations of the gut and nervous system in the animal model of persistent visceral pain caused by 2,4-dinitrobenzenesulfonic acid (DNBS). This agent, injected intrarectally, induced a colonic inflammation peaking on day 3 and remitting progressively from day 7. In concomitance with bowel inflammation, the animals developed visceral hypersensitivity, which persisted after colitis remission for up to three months. On day 14, the administration of pain-relieving drugs (injected intraperitoneally and intrathecally) revealed a mixed nociceptive, inflammatory and neuropathic pain originating from both the peripheral and central nervous system. At this time point, the colonic histological analysis highlighted a partial restitution of the tunica mucosa, transmural collagen deposition, infiltration of mast cells and eosinophils, and upregulation of substance P (SP)-positive nerve fibers, which were surrounded by eosinophils and MHC-II-positive macrophages. A significant activation of microglia and astrocytes was observed in the dorsal and ventral horns of spinal cord. These results suggest that the persistence of visceral pain induced by colitis results from maladaptive plasticity of the enteric, peripheral and central nervous systems. View Full-Text
Keywords: visceral hypersensitivity; inflammatory bowel disease; irritable bowel syndrome; microglia; astrocytes; immune system visceral hypersensitivity; inflammatory bowel disease; irritable bowel syndrome; microglia; astrocytes; immune system
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MDPI and ACS Style

Lucarini, E.; Parisio, C.; Branca, J.J.V.; Segnani, C.; Ippolito, C.; Pellegrini, C.; Antonioli, L.; Fornai, M.; Micheli, L.; Pacini, A.; Bernardini, N.; Blandizzi, C.; Ghelardini, C.; Di Cesare Mannelli, L. Deepening the Mechanisms of Visceral Pain Persistence: An Evaluation of the Gut-Spinal Cord Relationship. Cells 2020, 9, 1772. https://doi.org/10.3390/cells9081772

AMA Style

Lucarini E, Parisio C, Branca JJV, Segnani C, Ippolito C, Pellegrini C, Antonioli L, Fornai M, Micheli L, Pacini A, Bernardini N, Blandizzi C, Ghelardini C, Di Cesare Mannelli L. Deepening the Mechanisms of Visceral Pain Persistence: An Evaluation of the Gut-Spinal Cord Relationship. Cells. 2020; 9(8):1772. https://doi.org/10.3390/cells9081772

Chicago/Turabian Style

Lucarini, Elena; Parisio, Carmen; Branca, Jacopo J.V.; Segnani, Cristina; Ippolito, Chiara; Pellegrini, Carolina; Antonioli, Luca; Fornai, Matteo; Micheli, Laura; Pacini, Alessandra; Bernardini, Nunzia; Blandizzi, Corrado; Ghelardini, Carla; Di Cesare Mannelli, Lorenzo. 2020. "Deepening the Mechanisms of Visceral Pain Persistence: An Evaluation of the Gut-Spinal Cord Relationship" Cells 9, no. 8: 1772. https://doi.org/10.3390/cells9081772

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