Abstract
Acute inflammation is particularly relevant in the pathogenesis of visceral hypersensitivity associated with inflammatory bowel diseases. Glia within the enteric nervous system, as well as within the central nervous system, contributes to neuroplasticity during inflammation, but whether enteric glia has the potential to modify visceral sensitivity following colitis is still unknown. This work aimed to investigate the occurrence of changes in the neuron–glial networks controlling visceral perception along the gut–brain axis during colitis, and to assess the effects of peripheral glial manipulation. Enteric glia activity was altered by the poison fluorocitrate (FC; 10 µmol kg−1 i.p.) before inducing colitis in animals (2,4-dinitrobenzenesulfonic acid, DNBS; 30 mg in 0.25 mL EtOH 50%), and visceral sensitivity, colon damage, and glia activation along the pain pathway were studied. FC injection significantly reduced the visceral hyperalgesia, the histological damage, and the immune activation caused by DNBS. Intestinal inflammation is associated with a parallel overexpression of TRPV1 and S100β along the gut–brain axis (colonic myenteric plexuses, dorsal root ganglion, and periaqueductal grey area). This effect was prevented by FC. Peripheral glia activity modulation emerges as a promising strategy for counteracting visceral pain induced by colitis.
Highlights
Visceral pain was assessed in the animals by assigning a score to their abdominal withdrawal reflex (AWR) to colorectal distension (CRD), which was performed by progressively increase balloon volumes as a pressure stimulus to the colon
0.001; Figure alone did no alter expression are expressed as average relative fluorescence units (RFUs) ± standard error of the mean (SEM) per area unit of of n assessments
TRPV1of expression are expressed as average relative S100β fluorescence per area unit ofasnaassessments
Summary
Current theories suggest that functional remodeling of neural networks controlling visceral perception and immune activation contribute to the development of abdominal pain during colitis which persists long after acute inflammation has resolved. In this context, the release of proinflammatory mediators by macrophages and other immune cells infiltrating the intestinal mucosa concurs to drive neuroplastic changes [2], such as the increase in transient receptor potential vanilloid receptor type-1 (TRPV1) on nociceptors innervating the intestine, contributing. Enteric glial activity undergoes extensive changes during the intestinal inflammation that have the potential to alter the function of surrounding neural and non-neuronal cells and contribute to neuroinflammation and neurodegeneration associated with colitis [9,10,11]. Reactive enteric glia exhibits a pro-inflammatory phenotype and overexpression of the enteric glia-derived Ca+2 /Zn+2 -binding protein S100β has been linked to the onset and maintenance of intestinal inflammation in human colon [12]
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