A98 EXCITATION OF LUMBAR SPLANCHNIC AFFERENT NERVES BY FECAL SUPERNATANTS FROM INFLAMMATORY BOWEL DISEASE PATIENTS

Abstract

Abstract Background Increased excitability of extrinsic afferent nerves has emerged as an important cause of visceral pain during inflammatory bowel disease (IBD). However, little is understood regarding what role, if any, the intestinal microbiota plays in pain development during IBD. Therefore, we aimed to determine the effects of fecal supernatants (FS) from patients with IBD on lumbar splanchnic afferent nerves (LSN). Aims We aimed to determine the effects of fecal supernatants (FS) from patients with IBD on lumbar splanchnic afferent nerves (LSN). Methods Fecal samples from 8 patients with active IBD (4 Crohn’s disease (CD) patients and 4 ulcerative colitis (UC) patients) and 6 healthy volunteers (HV) were suspended in normal saline solution at 0.5gm/4 ml. In vitro extracellular recordings of action potential discharge were obtained from LSN of the distal colon from control mice. LSN afferents were classified based on their responses to colonic distention into low threshold (LT), high threshold (HT), wide dynamic range (WDR) and mechanically insensitive (MIS) units. FS was applied intraluminally for 20 min after which afferent nerve sensitivity for colonic distension was re-assessed. Results FS from IBD patients increased the basal firing frequency of afferent nerves compared to vehicle control (P value <0.0001 in both CD and UC experiments). Furthermore, FS from CD augmented the mechanosensitivity of the overall activity of the units with 35% increase in the units’ discharge compared to vehicle control with a significant effect on HT and MIS units. Conversely, FS from HV decreased the basal firing frequency of afferent nerves compared to vehicle control (P value < 0.01). Moreover, FS from HV induced 60% reduction in the mechanosensitivity of the overall activity of the units with a significant effect on HT and WDR units. Conclusions These results suggest that FS from IBD patients contain mediators that can activate LSN. These changes would lead to an increased afferent input to the CNS, which could exacerbate pain. On the other hand, control FS from HV contain mediators that suppress the activity of LSN. Further characterization these mediators has the potential to lead to new targets for pain management in IBD. Funding Agencies CCC, CIHR