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.
Highlights
Chronic and recurrent abdominal pain is commonly experienced in the general population, including children and adolescents
Visceral sensitivity was assessed by measuring the viscero-motor response (VMR) to colo-rectal distension (0.5–3 mL) at baseline as well as 7, 14, and 21 days after dinitrobenzenesulfonic acid (DNBS) injection (Figure 1a)
To investigate the characteristics of DNBS-induced pain, we evaluated over time (7, 14, and 21 days after DNBS injection; Figure 3a–c, respectively) the effects of the acute systemic administration of different drugs on visceral hypersensitivity
Summary
Chronic and recurrent abdominal pain is commonly experienced in the general population, including children and adolescents. Abdominal pain frequently results from prolonged enteric inflammatory processes, as in cases of inflammatory bowel diseases (IBDs) [2,3]. Bowel inflammation leads to enteric barrier breakdown, altered water/electrolyte secretion, changes in motility patterns, and visceral sensations, culminating in abdominal symptoms (diarrhea, cramping, and pain) [4]. The poor correlation between reported abdominal pain intensity and IBD activity raises close similarities with irritable bowel syndrome (IBS) [2,5], a symptom-based clinical condition defined by the persistence of abdominal pain and discomfort, with altered bowel habits, in the absence of any other disease [6]. The current therapeutic approaches to IBD and IBS symptoms, including psycho-nutritional and pharmacological treatments (bulking-agents, antidiarrheals, antispasmodics, antidepressants) [4,7], are almost ineffective against abdominal pain [8] which highly impacts the patient’s quality of life
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