1: Br J Pharmacol. 2007 Aug;151(7):1117-28. Epub 2007 Jun 11.

The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on
pain behaviour in rodent models of neuropathy.

Wallace VC, Segerdahl AR, Lambert DM, Vandevoorde S, Blackbeard J, Pheby T,
Hasnie F, Rice AS.

Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive
Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster
Hospital Campus, 369 Fulham Road, London, UK.

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.

PMID: 17558434 [PubMed - in process]

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