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

Abstract

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.

• Authors: Elena Lucarini, Carmen Parisio, Jacopo J V Branca, Cristina Segnani, Chiara Ippolito, Carolina Pellegrini, Luca Antonioli, Matteo Fornai, Laura Micheli, Alessandra Pacini, Nunzia Bernardini, Corrado Blandizzi, Carla Ghelardini, Lorenzo Di Cesare Mannelli
• Journal: Cells (Cells) Vol. 9 Issue 8 (07 24 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 32722246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Gastrointestinal Microbiome (physiology)
• Humans
• Male
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (physiopathology)
• Visceral Pain (physiopathology)