Role of Enteric Glia as Bridging Element between Gut Inflammation and Visceral Pain Consolidation during Acute Colitis in Rats

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.

Beneficial Effects of Eruca sativa Defatted Seed Meal on Visceral Pain and Intestinal Damage Resulting from Colitis in Rats

“…As mentioned above, enteric glial cells, which become activated during colitis in rats [ 34 , 54 ], are able to modulate both neuronal and immune functions and participates in visceral sensitivity regulation [ 18 , 55 , 56 ] by modulating different pathways within the gut [ 27 , 57 ]. E. sativa treatment, turning off both glia and MCs signaling, could counteract the perpetuation and the amplification of the inflammatory response, promoting tissue healing and reducing chronic pain associated with colitis, as observed in our recent study [ 17 ]. Indeed, the treatment with E. sativa DSM significantly reduced the number of mast cells in the colon of DNBS animals, confirming the regulation of the immune response as one of the mechanisms by which E. sativa’s active components promote gut healing.…”

“…The present work is aimed at evaluating the therapeutic potential of E. sativa DSM in the management of the persistent visceral pain resulting from inflammatory damage to the colon. Colitis induced by 2,4-dinitrobenzenesulfonic acid (DNBS) injection in rats is indeed associated with the development of a visceral hypersensitivity that persists after colitis remission because of the establishment of concomitant alterations in the immune response, microbiota metabolism, nerve signaling, and glia function both in animals and humans [ 14 , 15 , 16 , 17 ].…”

The Efficacy of Camelina sativa Defatted Seed Meal against Colitis-Induced Persistent Visceral Hypersensitivity: The Relevance of PPAR α Receptor Activation in Pain Relief

“…Moreover, during inflammatory conditions, enteric glia surrounding neurons in the gut can undergo extensive changes which alter the interaction with the heterogenous cellular environment, contributing to perpetuating visceral hyperalgesia [ 50 , 51 , 52 , 53 ]. Enteric glia activation can be highlighted in animals and humans by changes in the expression of peculiar biological markers, such as GFAP [ 52 , 53 , 54 ]. In Figure 8 B, an up-regulation of GFAP expression in DNBS-treated rats with respect to controls (vehicle) can be observed.…”

“…At the same time, the treatment with camelina was able to partially reduce the intestinal damage caused by colitis and strongly lower the number of mast cells infiltrating the tissue. This last parameter has high relevance in the context of visceral pain, which has been linked to a deregulation of mast cell function [ 52 , 53 , 71 , 72 ]. The control of mast cell activity is also important in the maintenance of gut homeostasis since these cells are the crossroads of many physiological processes playing a key role in the regulation of the intestinal barrier, secretion, and gut motility [ 48 , 73 ].…”

The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?

“…Furthermore, in a recent report using a rat model of colitis induced by intracolonic 2,4-dinitrobenzene-sulfonic acid (DNBS), Lucarini et al [ 72 ] have demonstrated the essential role of enteric glia in the development of visceral hypersensitivity associated with intestinal inflammation. In this work, the gliotoxin fluorocitrate reduced intestinal damage and visceral sensitivity.…”