Paper Information

Title: 

EFFECTS OF ENDOCANNABINOID HYDROLYSIS INHIBITION ON PAIN MODULATION IN A RAT MODEL OF CHOLESTASIS

Type: POSTER
Author(s): ABD ELAHI F.,HASANIN PARISA*,DARIANI SAEID SH.
 
 *DEPARTMENT OF BIOLOGY, SCHOOL OF BASIC SCIENCES, BU-ALI SINA UNIVERSITY, HAMADAN, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

Cholestasis is associated with increased activity of the endogenous opioid system that results in analgesia. Endocannabinoid system can reduce pain sensitivity. The use of inhibitors of endocannabinoid metabolism is a novel means of pharmacologically increasing endocannabinoid levels. Considering the interaction that has been shown between the endogenous opioid and endocannabinoid systems in nociception processing, we studied the effects of URB597, a selective inhibitor of FAAH (fatty acid amide hydrolase), on modulation of nociception in a model of elevated endogenous opioid tone, cholestasis. Cholestasis was induced by ligation of the main bile duct usingtwo ligatures and then transaction of the duct at the midpoint between them.
Seven days after surgery, tail-flick latencies were measured at 60 minutes after drug administration. A significant increase (P<0.001) in nociception threshold was observed in cholestatics compared to unoperated and sham groups. Administration of URB597 (0.3 mg/kg,i.p.) in cholestatic animals significantly (P<0.001) increased tail-flick latency compared to the vehicle treated cholestatic group. URB597 injection to unoperated and sham groups caused a significant (P<0.05, P<0.05) increase in tail-flick latency compared to their respective vehicle treated groups. The antinociceptive effect of URB597 was blocked by coadministration of a cannabinoid CB1 receptor antagonist, AM251 (1 mg/kg,i.p.) with URB597. These data showed that URB597 as a FAAH inhibitor potentiates antinociception induced by cholestasis in tail-flick test and that the inhibitory effects of URB597 in this model are mediated by cannabinoid CB1 receptors.

 
Keyword(s): CHOLESTASIS, HYDROLYSIS, ENDOCANNABINOID, ANTINOCICEPTION, RATS
 
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