The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy
(2007) British Journal of Pharmacology — Vol. 151, n° 7, p. 1117-1128 (2007)
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- 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 (10mgkg(-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 mgkg(-1)). The CB1 receptor antagonist SR141716a (1 mgkg(-1)) and the CB2 receptor antagonist SR144528 (1 mgkg(-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 mgkg(-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.
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Wallace, V. C. J., Segerdahl, A. R., Lambert, D., Vandevoorde, S., Blackbeard, J., Pheby, T., Hasnie, F., & Rice, A. S. C. (2007). The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. British Journal of Pharmacology, 151(7), 1117-1128. https://doi.org/10.1038/sj.bjp.0707326 (Original work published 2007)