Introduction: Inflammatory bowel disease is characterized by remitting and relapsing bouts of intestinal inflammation accompanied by sensory and motor dysfunction that persists beyond the active periods of inflammation. Evidence suggests that neural pathways of the Gut-Brain Axis, particularly the sensory and sympathetic nervous system, are involved in pathophysiology, but until recently technical restrictions have limited our understanding of the underlying neural circuit mechanisms. In this study, we examined how sensory-sympathetic circuits are modified by colitis and how these alterations contribute to dysfunction during both active inflammation and post-inflammatory recovery. Methods: E2a-GCaMP mice were treated with vehicle or 3% dextran sodium sulfate (DSS) for 5 days to induce experimental colitis and switched to normal drinking water. Mice were assessed at two time points: Day 7 (two days after ending DSS treatment), representing active inflammation, and Day 21 to represent recovery. Inflammation and mucosal damage were evaluated using disease activity index scores and hematoxylin and eosin (H&E) staining. Colon motility was assessed in vivo via colonic bead expulsion and ex vivo using whole-colon preparations. We performed Ca 2+ imaging of sympathetic motor neurons in prevertebral ganglia (PVG) and sensory neurons in dorsal root ganglia (DRG) neurons in ex vivo preparations that preserve extrinsic neural circuitry with the colon (intestinofugal-sympathetic and spinal cord-sympathetic pathways). Results: Histological analysis confirmed hallmark features of colitis, including colon shortening, immune infiltration, and mucosal damage at 7 days post-DSS (p< 0.05, n=3–4), which resolved after recovery. During active inflammation, in vivo colon transit time was significantly faster, and this persisted after recovery (p< 0.05, n=7-9). Ex vivo motility assays in isolated colons also revealed DSS-induced dysmotility during active inflammation, but the irregular colon motor complexes became normal after recovery (p< 0.05, n=7-9), suggesting that extrinsic neural pathways contribute to prolonged dysmotility. In preparations without the spinal cord, PVG neurons exhibited increased activity and increased responses to distension during active inflammation but returned to baseline after recovery (p< 0.05, n=3-4), suggesting alternative sensory-PVG pathways contribute to persistent dysmotility. In preparations with spinal circuits intact, thoracolumbar (TL), but not lumbosacral (LS), DRG sensory neurons were hypersensitive to colonic distension during inflammation (p< 0.05, n=8-9). Furthermore, TL spinal stimulation evoked more responses in PVG neurons during active inflammation, but this was associated with decreased inhibition of ENS motor circuits (p< 0.05, n=6-7) and increased Ca 2+ signaling in the epithelium (p< 0.05, n=5), suggesting shifts in TL spinal-sympathetic motor output. Preliminary studies show an increase in spontaneous activity of TL DRG neurons in recovery that does not occur at LS levels (p< 0.05, n=3-6), which suggests that thoracolumbar spinal pathways remain hyperexcitable after recovery.Conclusions: Our findings indicate that TL spinal pathways associated with sympathetic motor outflow contribute to pain and dysmotility during active inflammation and may contribute to the post-inflammatory recovery processes that seem to go awry in IBD patients with relapsing inflammation. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Morales‐Soto et al. (Fri,) studied this question.