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- Title
The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy.
- Authors
Wallace, V. C. J.; Segerdahl, A. R.; Lambert, D. M.; Vandevoorde, S.; Blackbeard, J.; Pheby, T.; Hasnie, F.; Rice, A. S. C.
- Abstract
Background and Purpose:Cannabinoids are associated with analgesia in acute and chronic pain states. A spectrum of central cannabinoid (CB1) 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 CB1 receptor antagonist SR141716a (1 mg kg−1) and the CB2 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-α 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.British Journal of Pharmacology (2007) 151, 1117–1128; doi:10.1038/sj.bjp.0707326; published online 11 June 2007
- Subjects
CANNABINOIDS; NEUROPATHY; HEMP; ANALGESIA; CHRONIC pain; PHARMACODYNAMICS; HIV; VARICELLA-zoster virus; AMIDES; AMINES; ANIMAL behavior; ANIMAL experimentation; CELL receptors; COMPARATIVE studies; DRUGS; DOSE-effect relationship in pharmacology; ETHANOLAMINES; FATTY acids; GABA; HETEROCYCLIC compounds; HYDROCARBONS; INJECTIONS; LEG; RESEARCH methodology; MEDICAL cooperation; NEUROTRANSMITTERS; PAIN; PIPERIDINE; PROTEINS; RATS; RESEARCH; SCIATICA; TEMPERATURE; EVALUATION research; PAIN measurement; CARBOCYCLIC acids; ZALCITABINE (Drug); INDOLE compounds; PAIN threshold; CHEMICAL inhibitors; PREVENTION
- Publication
British Journal of Pharmacology, 2007, Vol 151, Issue 7, p1117
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0707326