Tags

Type your tag names separated by a space and hit enter

Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models.
Br J Pharmacol. 2006 Feb; 147(3):281-8.BJ

Abstract

While cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central CB(1) 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.

Authors+Show Affiliations

Pain Management Research Institute, Northern Clinical School, The University of Sydney, NSW, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16331291

Citation

Jayamanne, Angelo, et al. "Actions of the FAAH Inhibitor URB597 in Neuropathic and Inflammatory Chronic Pain Models." British Journal of Pharmacology, vol. 147, no. 3, 2006, pp. 281-8.
Jayamanne A, Greenwood R, Mitchell VA, et al. Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. Br J Pharmacol. 2006;147(3):281-8.
Jayamanne, A., Greenwood, R., Mitchell, V. A., Aslan, S., Piomelli, D., & Vaughan, C. W. (2006). Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. British Journal of Pharmacology, 147(3), 281-8.
Jayamanne A, et al. Actions of the FAAH Inhibitor URB597 in Neuropathic and Inflammatory Chronic Pain Models. Br J Pharmacol. 2006;147(3):281-8. PubMed PMID: 16331291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models. AU - Jayamanne,Angelo, AU - Greenwood,Ruth, AU - Mitchell,Vanessa A, AU - Aslan,Sevda, AU - Piomelli,Daniele, AU - Vaughan,Christopher W, PY - 2005/12/7/pubmed PY - 2006/12/27/medline PY - 2005/12/7/entrez SP - 281 EP - 8 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 147 IS - 3 N2 - While cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central CB(1) 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/16331291/Actions_of_the_FAAH_inhibitor_URB597_in_neuropathic_and_inflammatory_chronic_pain_models_ L2 - https://doi.org/10.1038/sj.bjp.0706510 DB - PRIME DP - Unbound Medicine ER -