Lack of effect of chronic pre-treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system

Okine, Bright N, Norris, Leonie M, Woodhams, Stephen, Burston, James, Patel, Annie, Alexander, Stephen PH, Barrett, David A, Kendall, David A, Bennett, Andrew J and Chapman, Victoria 2012. Lack of effect of chronic pre-treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system. British Journal of Pharmacology 167 (3) , pp. 627-640. 10.1111/j.1476-5381.2012.02028.x

Full text not available from this repository.

Abstract

BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor‐mediated side effects. HerSingle, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle‐treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan‐induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N‐acylphosphatidylethanolamine phospholipase D (NAPE‐PLD) in the spinal cord and attenuated carrageenan‐induced spinal pro‐inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain. e, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre‐treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan‐induced inflammatory pain behaviour and spinal pro‐inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Wiley: 12 months
ISSN:	0007-1188
Date of Acceptance:	25 April 2012
Last Modified:	10 Jul 2018 13:30
URI:	https://orca.cardiff.ac.uk/id/eprint/112062

Citation Data

Cited 52 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item