TNBS-induced inflammation modulates the function of one class of low-threshold rectal mechanoreceptors in the guinea pig

Abstract

The effects of trinitrobenzene sulfonic acid (TNBS)-induced inflammation on specialized, low-threshold, slowly adapting rectal mechanoreceptors were investigated in the guinea pig. Under isoflurane anesthesia, 300 microl saline or TNBS (15 mg/ml) in 30% ethanol was instilled 7 cm from the anal sphincter. Six or 30 days later, single unit extracellular recordings were made from rectal nerve trunks in flat-sheet in vitro preparations attached to a mechanical tissue stretcher. TNBS treatment caused macroscopic ulceration of the rectal mucosa at 6 days, which fully resolved by 30 days. Muscle contractility was unaffected by TNBS treatment. At 6 days posttreatment, responses of low-threshold rectal mechanoreceptors to circumferential stretch were increased, and the proportion of afferents responding with von Frey hair thresholds <or=0.1 mN and mechanoreceptor excitability in response to electrical stimulation were increased in TNBS-treated tissue, suggesting increased sensitivity of the mechanotransducer. Mechanoreceptor function at 30 days posttreatment was in most cases unchanged. The inflammatory mediator prostaglandin E(2) (1 microM) activated mechanoreceptors (6 days) in conjunction with contractile activity, but capsaicin (1 microM) failed to activate mechanoreceptors. Bradykinin (1 microM) activated mechanoreceptors independently of contractile activity and responses to stretch were increased in the presence of bradykinin. Both capsaicin and bradykinin activated unidentified stretch-insensitive afferents independently of contractile activity. Mechanoreceptor function is modulated at 6 days posttreatment but not at 30 days, suggesting a moderate increase in mechanoreceptor sensitivity in inflamed tissue but not after recovery. Other unclassified stretch-insensitive afferents are responsive to inflammatory mediators and capsaicin and may be involved in aspects of visceral sensation.

Post‐inflammatory modification of colonic afferent mechanosensitivity

“…Histological pathology in the acute phase includes ulceration, goblet cell depletion, oedema and increased granulocyte activity. 54,55,57,[61][62][63][64][65][66][67] The inflammatory aspects resulting from TNBS instillation are predominantly mediated by a Th1 pro-inflammatory cytokine response, consistent with clinical PI-IBS observations. 68 Despite the close correlation between results obtained using TNBS across several species, several considerations must be made prior to treatment.…”

“…A milder sensitization was observed in those afferents that respond to light mucosal stroking (mucosal afferents), whereas those afferents that respond with low thresholds to circular stretch (muscular afferents) are not affected in either mouse or guinea-pig models. 55,63 Remarkably, afferents residing in the outer wall of the colon, furthest from the site of damage, show the greatest changes.…”

Post-inflammatory colonic afferent sensitisation: different subtypes, different pathways and different time courses

“…This suggests that in order to observe upregulation of mechanosensory mechanisms, the choice of species and/or the inflammatory agent is important. Our recent study in the guinea-pig24 showed, in a TNBS model, that rectal muscular afferents were sensitised to distension in the acute phase of inflammation, but unaffected after recovery. In this case our stimulus is the same but the species is different, but there is agreement that long-term changes in mechanosensitivity are absent in low-threshold distension-sensitive subtypes of afferents.…”

Citrobacter rodentium colitis evokes post‐infectious hyperexcitability of mouse nociceptive colonic dorsal root ganglion neurons

“…including those at day 10 where overall differences were not seen). Recent studies suggest important differences may exist between specific fibre types and pelvic compared to splanchnic nerves in response to inflammation (Lynn et al 2008; Hughes et al 2009). A previous study of intestinal afferents has also shown a correlation between mechanosensitivity and neuronal hyperexcitability (Keating et al 2008), although the current study is the first to identify one of the candidate ion channels (i.e.…”