URB597, an inhibitor of fatty acid amide hydrolase, reduces hyperalgesia in diabetic rats.

Abstract

Diabetic rats display increased pain responses after injection of formalin into the paw or thermal stimulation of the tail, suggesting the presence of hyperalgesia. In this study, we investigated the efficacy of URB597 (0.1, 0.3, and 0.5 mg/kg, i.p.), an inhibitor of endocannabinoids metabolism, on 2 models of experimental hyperalgesia in streptozotocin (STZ)-induced diabetic rats. Animals were divided into control, URB597-treated control (0.1, 0.3, and 0.5 mg/kg), diabetic, and URB597-treated diabetic (0.1, 0.3, and 0.5 mg/kg) groups. Formalin and tail-flick tests were performed 4 and 8 weeks after the onset of hyperglycemia, respectively. Diabetes caused significant hyperalgesia during these tests. URB597 (0.3 and 0.5 mg/kg) reversed chemical and thermal hyperalgesia in diabetic rats. Administration of URB597 at a dose of 0.1 mg/kg did not alter pain-related behaviors in control and diabetic groups compared with those of the respective control groups. URB597 treatment did not affect body weight or plasma glucose level of treated animals compared with nontreated animals. This study shows that increasing endocannabinoid neurotransmission with URB597 displays efficacy in chemical and thermal models of diabetic hyperalgesia. It also suggests that URB597 is a promising tool for treatment of painful diabetic neuropathy.

• Authors: Parisa Hasanein, Mohsen Parviz, Mansoor Keshavarz, Ali Roohbakhsh
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 87 Issue 6 Pg. 432-9 (Jun 2009) ISSN: 1205-7541 [Electronic] Canada
• PMID: 19526037 (Publication Type: Journal Article)

Chemical References

• Benzamides
• Blood Glucose
• Cannabinoid Receptor Modulators
• Carbamates
• Enzyme Inhibitors
• cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
• Amidohydrolases
• fatty-acid amide hydrolase

Topics

• Amidohydrolases (antagonists & inhibitors)
• Animals
• Benzamides (administration & dosage, pharmacology, therapeutic use)
• Blood Glucose (analysis)
• Body Weight (drug effects)
• Cannabinoid Receptor Modulators (metabolism)
• Carbamates (administration & dosage, pharmacology, therapeutic use)
• Diabetes Mellitus, Experimental (blood, complications, enzymology)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use)
• Hyperalgesia (enzymology, etiology, prevention & control)
• Injections, Intraperitoneal
• Male
• Pain Measurement
• Pain Threshold
• Rats
• Rats, Wistar
• Temperature