Nerve growth factor-induced hyperalgesia counteracted by palmitoyethanolamide

W Paul Farquhar-Smith and Andrew S C Rice describe in their 2003 paper under the title: “A novel neuroimmune mechanism in cannabinoid-mediated attenuation of nerve growth factor-induced hyperalgesia” (Anesthesiology. 2003 Dec ;99 (6):1391-401) the relation between NGF, pain and palmitoylethanolamide.

They start pointing pout that Nerve growth factor (NGF) is central to processes involved in an inflammatory hyperalgesia. The administration of exogenous NGF induces hyperalgesia that is dependent on local influx of white blood cells.

The effects of administration of the cannabinoid anandamide and the lipid endogenous palmitoylethanolamide on an NGF-induced hyperalgesia and neutrophil accumulation were examined by the authors in a special animal model in rats based on noxious heat stimuli.

Anandamide or palmitoylethanolamide at doses of 10 and 25 mg/kg were given (intraperitoneally) immediately after NGF. CB1 and CB2 receptor antagonists were coadministered with the higher dose of the compounds.

Administration of NGF reduced hyperalgesia. Anandamide and palmitoylethanolamide significantly could reduced this hyperalgesia.

The action of anandamide was clearly CB1 receptor-mediated. SR144528 abrogated the action of palmitoylethanolamide, but this CB2 antagonist is quite aspecific.

NGF also provoked neutrophil accumulation in the injected paw, and palmitoylethanolamide significantly could reduced neutrophil accumulation, whereas anandamide was without effect.

From this experiment we can see that NGF induced a thermal hyperalgesia that was attenuated by anandamide and palmitoylethanolamide. Only palmitoylethanolamide could also reduce the while bloodcell influx.

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