Capsaicin-sensitive mechanisms in the modulation of rat colonic vascular permeability under physiological and pathological conditions.
Inflammatory bowel disease (IBD) causes a prolonged life-quality reduction of patients and high costs for health services. The aim of this study was to explore the possible involvement of peptidergic capsaicin-sensitive afferent nerves (CSN) in the pathogenesis of IBD. For the defunctionalization of colonic CSN, the lower part of the colon (1-4 cm from the anus) was exposed through a midline laparotomy and small pieces of gelfoam moistened with a solution of capsaicin (1%, 100 microL) was applied onto the serosal surface for 30 min in male Wistar rats. Colonic vascular permeability was assessed by measuring the extravasation of [125I] human serum albumin (2 microCi/kg, i.v., 2 h prior to killing). Two months after capsaicin treatment a significant increase in albumin extravasation was found in the lower (P < 0.005), but not in the upper (5-8 cm from the anus) part of the colon as compared to the sham-operated control. Intrarectal (8 cm from anus) administration of trinitrobenzene-sulphonic acid (TNBS; 30 mg/rat) induced similar plasma leakage in the lower and upper colon of control (CSN-intact) rats (P < 0.001) 1 week later. TNBS + ethanol (50%) produced further extravasation throughout the colon (P < 0.001) of CSN-intact animals. In the lower colon of capsaicin-pretreated rats TNBS-alone provoked an increase in plasma extravasation (P < 0.001) similar to that caused by TNBS + ethanol in CSN-intact rats. In the upper colon there was no difference in the effect of TNBS-alone on plasma leakage between control (CSN-intact) and CSN-depleted rats. The results suggest that capsaicin-sensitive nerves may play a significant protective/anti-inflammatory role in the colon under normal and pathological conditions.
Szepes
Z
Z
First Department of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Kiss
J
J
Molnár
T
T
Lamarque
D
D
Jancsó
G
G
László
F
F
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000633:toxicity; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000098:blood supply* / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity; D008297:Male; D009479:Neuropeptides / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
D000418:Albumins; D002492:Central Nervous System Depressants; D009479:Neuropeptides; D000431:Ethanol; D002211:Capsaicin