Intestinal inflammation and activation of sensory nerve pathways: a functional and morphological study in the nematode infected rat

Background-In the rat, gastric distension elicits an intensity dependent ps eudoaffective bradycardia mediated via capsaicin sensitive afferent and cho linergic efferent vagal pathways. Inflammation alters visceral perception a lthough the mediators responsible have not been identified. In the nematode infected rat, there is a substantial increase in neuronal substance P (SP) content of the gut. Aims-To examine the effects of inflammation on perception of a noxious visc eral stimulus and on SP and neurokinin 1 (NK-1) receptor immunoreactivity ( JR) in visceral afferent pathways. Methods-Immunohistochemistry was performed on sections from the jejunum, do rsal root ganglia (DRG), and spinal cord (TI-LI) using SP and NK-1 rabbit p olyclonal antibodies. In the DRG, the number of SP-IR or NK-I-IR neurones p er section was visually quantified. The pseudoaffective cardiac reflex resp onse to gastric stimulation was compared in control and Trichinella spirali s infected rats. Results-Intestinal inflammation induced a rightward shift in the intensity dependent bradycardic response to gastric distension. This was associated w ith a marked increase in SP-IR not only in the gut wall but also in the DRG and dorsal horn of the spine. In contrast, NK-1-IR was not increased in th e gut wall. Moreover, inflammation evoked a decrease in NK-1-IR in the dors al horn. No NK-1-IR was identified in the DRG of either control or infected animals. Conclusions-Intestinal inflammation modulates the capsaicin sensitive pseud oaffective autonomic response to gastric distension, increases SP-IR in aff erent pathways, and downregulates dorsal horn NK-I-IR. As the pseudoaffecti ve response is capsaicin sensitive, the rightward shift of the response is likely the consequence of the decrease in NK-1 receptors in the sensory pat hways.