Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models
Article first published online: 29 JAN 2009
2006 British Pharmacological Society
British Journal of Pharmacology
Volume 147, Issue 3, pages 281–288, February 2006
How to Cite
Jayamanne, A., Greenwood, R., Mitchell, V. A., Aslan, S., Piomelli, D. and Vaughan, C. W. (2006), Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. British Journal of Pharmacology, 147: 281–288. doi: 10.1038/sj.bjp.0706510
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received September 2, 2005, Revised September 29, 2005, Accepted September 30, 2005)
- fatty-acid amide hydrolase
While cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central CB1 receptor-mediated motor and psychotropic side effects. The actions of endocannabinoids, such as anandamide are terminated by removal from the extracellular space, then subsequent enzymatic degradation by fatty-acid amide hydrolase (FAAH). In the present study, we compared the effect of a selective FAAH inhibitor, URB597, to that of a pan-cannabinoid receptor agonist HU210 in rat models of chronic inflammatory and neuropathic pain.
Systemic administration of URB597 (0.3 mg kg−1) and HU210 (0.03 mg kg−1) both reduced the mechanical allodynia and thermal hyperalgesia in the CFA model of inflammatory pain. In contrast, HU210, but not URB597, reduced mechanical allodynia in the partial sciatic nerve-ligation model of neuropathic pain. HU210, but not URB597, produced a reduction in motor performance in unoperated rats.
The effects of URB597 in the CFA model were dose dependent and were reduced by coadministration with the cannabinoid CB1 antagonist AM251 (1 mg kg−1), or the CB2 and SR144528 (1 mg kg−1). Coadministration with AM251 plus SR144528 completely reversed the effects of URB597.
These findings suggest that the FAAH inhibitor URB597 produces cannabinoid CB1 and CB2 receptor-mediated analgesia in inflammatory pain states, without causing the undesirable side effects associated with cannabinoid receptor activation.
British Journal of Pharmacology (2006) 147, 281–288. doi:10.1038/sj.bjp.0706510