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BACKGROUND AND PURPOSE: Cannabinoids are associated with analgesia in acute and chronic pain states. A spectrum of central cannabinoid (CB(1)) receptor-mediated motor and psychotropic side effects limit their therapeutic potential. Here, we investigate the analgesic effect of the palmitoylethanolamide (PEA) analogue, palmitoylallylamide (L-29), which via inhibition of fatty acid amide hydrolase (FAAH) may potentiate endocannabinoids thereby avoiding psychotropic side effects. EXPERIMENTAL APPROACH: The in vivo analysis of the effect of L-29 on measures of pain behaviour in three rat models of neuropathic pain. KEY RESULTS: Systemically administered L-29 (10 mg kg(-1)) reduced hypersensitivity to mechanical and thermal stimuli in the partial sciatic nerve injury (PSNI) model of neuropathic pain; and mechanical hypersensitivity in a model of antiretroviral (ddC)-associated hypersensitivity and a model of varicella zoster virus (VZV)-associated hypersensitivity. The effects of L-29 were comparable to those of gabapentin (50 mg kg(-1)). The CB(1) receptor antagonist SR141716a (1 mg kg(-1)) and the CB(2) receptor antagonist SR144528 (1 mg kg(-1)) reduced the effect of L-29 on hypersensitivity in the PSNI and ddC models, but not in the VZV model. The peroxisome proliferator-activated receptor-alpha antagonist, MK-886 (1 mg kg(-1)), partially attenuated the effect of L-29 on hypersensitivity in the PSNI model. L-29 (10 mg kg(-1)) significantly attenuated thigmotactic behaviour in the open field arena without effect on locomotor activity. CONCLUSIONS AND IMPLICATIONS: L-29 produces analgesia in a range of neuropathic pain models. This presents L-29 as a novel analgesic compound that may target the endogenous cannabinoid system while avoiding undesirable side effects associated with direct cannabinoid receptor activation.

Original publication

DOI

10.1038/sj.bjp.0707326

Type

Journal article

Journal

Br J Pharmacol

Publication Date

08/2007

Volume

151

Pages

1117 - 1128

Keywords

Amides, Amines, Animals, Behavior, Animal, Camphanes, Cyclohexanecarboxylic Acids, Dose-Response Relationship, Drug, Endocannabinoids, Ethanolamines, Gabapentin, Hindlimb, Indoles, Injections, Intraperitoneal, Male, PPAR alpha, Pain, Pain Measurement, Pain Threshold, Palmitic Acids, Physical Stimulation, Piperidines, Pyrazoles, Rats, Rats, Wistar, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Rimonabant, Sciatic Neuropathy, Temperature, Zalcitabine, gamma-Aminobutyric Acid