The Vanilloid Receptor Initiates and Maintains Colonic Hypersensitivity Induced by Neonatal Colon Irritation in Rats

Background & Aims: Robust chemical or mechanical irritation of the colon of neonatal rats leads to chronic visceral hypersensitivity. The clinical and physiologic relevance of such noxious stimulation in the context of human irritable bowel syndrome is questionable. The aims of this study were to determine whether mild chemical irritation of the colon of neonatal rats produced persistent changes in visceral sensitivity and to evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in the initiation and maintenance of visceral hypersensitivity. Methods: Ten-day-old rat pups received an intracolonic infusion of 0.5% acetic acid in saline. TRPV1 inhibitors were administered 30 minutes before acetic acid sensitization. Sensitivity of the colon to balloon distention (CRD) in adults was measured by grading their abdominal withdrawal reflex and electromyographic responses. In adult rats, TRPV1 antagonist was injected intraperitoneally 30 minutes before CRD. Results: Neonatal acetic acid treatment resulted in higher sensitivity to CRD in adult rats compared with controls in the absence of histopathologic signs of inflammation. Treatment of colons of adult rats with acetic acid did not produce persistent sensitization. Antagonism of the TRPV1 before neonatal administration of acetic acid and after established visceral hypersensitivity attenuated sensitivity to CRD. TRPV1 expression was increased in dorsal root ganglia–containing colon afferent neurons. Conclusions: We have described a new model for persistent colonic sensory dysfunction following a transient noxious stimulus in the neonatal period and a potentially important role for TRPV1 in initiation and maintenance of persistent visceral hypersensitivity.

Abbreviations used in this paper: ANOVA, analysis of variance, AWR, abdominal withdrawal reflex, CRD, colorectal distention, DII, 1,1′-dioleyl-3,3,3′,3-tetramethylindocarbocyanine methanesulfonate, DRG, dorsal root ganglia, EMG, electromyographic, IBS, irritable bowel syndrome, IFN, interferon, IL, interleukin, I-RTX, 5′-iodoresiniferatoxin, LS, lumbar sacral, MPO, myeloperoxidase, PFA, paraformaldehyde, P10, 10-day-old rat pups, TL, thoracolumbar, TRPV1, transient receptor potential vanilloid 1