Faculty Collaboration Database

Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-colitis. J Gastrointest Surg 2004 Nov;8(7):842-7; discussion 847-8

Date

11/09/2004

Pubmed ID

15531237

DOI

10.1016/j.gassur.2004.07.011

Scopus ID

2-s2.0-16644364367 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

Primary sensory neurons are important in regard to the initiation and propagation of intestinal inflammation. The vanilloid receptor subtype-1 (VR-1) is a cation channel located on the sensory nerves that, when stimulated, release proinflammatory peptides. Previous reports have indicated that inhibition of VR-1 with capsazepine (CPZ), a VR-1 antagonist, attenuates dextran sodium sulfate (DSS) colitis in rats. DSS-induced colitis resembles ulcerative colitis with regard to its pathologic features. In this study, we examined the effect of CPZ on trinitrobenzene sulfonic acid (TNBS)-induced colitis, an experimental model of intestinal inflammation that most closely resembles the histologic and microscopic features of Crohn's disease. Colitis was induced by administering a single enema of 100 mg/kg TNBS in 50% ethanol via catheter to lightly anesthetized rats. Subsets of rats were treated with either 1 micromol/kg/ml of CPZ or CPZ-vehicle via enema for 6 days. Seven days after TNBS administration, rats were sacrificed and inflammation was assessed using a validated macroscopic damage score (MDS) and by measuring myeloperoxidase (MPO) activity. In addition, histologic examination was performed. TNBS administration resulted in reproducible chronic erosive lesions extending into the muscularis propria and extensive recruitment of neutrophils in the distal colon. MDS and MPO scores were considerably elevated in the TNBS colons when compared with the TNBS vehicle animals. TNBS rats treated with CPZ enemas exhibited a substantial reduction in MDS and MPO scores and demonstrated dramatically improved pathologic findings. Topical CPZ resulted in considerable attenuation of TNBS-induced colitis. These results support the role of VR-1 and sensory neurons with regard to intestinal inflammation.

Author List

Fujino K, Takami Y, de la Fuente SG, Ludwig KA, Mantyh CR

Author

Kirk A. Ludwig MD Chief, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Capsaicin
Colitis
Colon
Nociceptors
Peroxidase
Rats
Rats, Sprague-Dawley
Receptors, Drug
TRPV Cation Channels
Trinitrobenzenesulfonic Acid