Deoxycholic acid activates colonic afferent nerves via 5-HT3 receptor-dependent and -independent mechanisms.

Increased bile acids in the colon can evoke increased epithelial secretion resulting in diarrhea, but little is known about whether colonic bile acids contribute to abdominal pain. This study aimed to investigate the mechanisms underlying activation of colonic extrinsic afferent nerves and their neuronal cell bodies by a major secondary bile acid, deoxycholic acid (DCA). All experiments were performed on male C57BL/6 mice. Afferent sensitivity was evaluated using in vitro extracellular recordings from mesenteric nerves in the proximal colon (innervated by vagal and spinal afferents) and distal colon (spinal afferents only). Neuronal excitability of cultured dorsal root ganglion (DRG) and nodose ganglion (NG) neurons was examined with perforated patch clamp. Colonic 5-HT release was assessed using ELISA, and 5-HT immunoreactive enterochromaffin (EC) cells were quantified. Intraluminal DCA increased afferent nerve firing rate concentration dependently in both proximal and distal colon. This DCA-elicited increase was significantly inhibited by a 5-HT3 antagonist in the proximal colon but not in the distal colon, which may be in part due to lower 5-HT immunoreactive EC cell density and lower 5-HT levels in the distal colon following DCA stimulation. DCA increased the excitability of DRG neurons, whereas it decreased the excitability of NG neurons. DCA potentiated mechanosensitivity of high-threshold spinal afferents independent of 5-HT release. Together, this study suggests that DCA can excite colonic afferents via direct and indirect mechanisms but the predominant mechanism may differ between vagal and spinal afferents. Furthermore, DCA increased mechanosensitivity of high-threshold spinal afferents and may be a mechanism of visceral hypersensitivity.NEW & NOTEWORTHY Deoxycholic acid (DCA) directly excites spinal afferents and, to a lesser extent, indirectly via mucosal 5-HT release. DCA potentiates mechanosensitivity of high-threshold spinal afferents independent of 5-HT release. DCA increases vagal afferent firing in proximal colon via 5-HT release but directly inhibits the excitability of their cell bodies.

Cholinergic signaling plasticity maintains viscerosensory responses during Aspiculuris tetraptera infection in mice small intestine.

Intestinal parasites alter gastrointestinal (GI) functions like the cholinergic function. Aspiculuris tetraptera is a pinworm frequently observed in laboratory facilities, which infests the mice cecum and proximal colon. However, little is known about the impact of this infection on the GI sensitivity. Here, we investigated possible changes in spontaneous mesenteric nerve activity and on the mechanosensitivity function of worm-free regions of naturally infected mice with A. tetraptera. Infection increased the basal firing of mesenteric afferent nerves in jejunum. Our findings indicate that nicotinic but not muscarinic receptors, similarly affect spontaneous nerve firing in control and infected animals; these axons are mainly vagal. No difference between groups was observed on spontaneous activity after nicotinic receptor inhibition. However, and contrary to the control group, during infection, the muscarinic signaling was shown to be elevated during mechanosensory experiments. In conclusion, we showed for the first time that alterations induced by infection of the basal afferent activity were independent of the cholinergic function but changes in mechanosensitivity were mediated by muscarinic, but not nicotinic, receptors and specifically by high threshold nerve fibers (activated above 20mmHg), known to play a role in nociception. These plastic changes within the muscarinic signaling would function as a compensatory mechanism to maintain a full mechanosensory response and the excitability of nociceptors during infection. These changes indicate that pinworm colonic infection can target other tissues away from the colon.