The reduction in NGF exerted by PEA in our model can be explained with different mechanisms of action, an ALIA mechanism played on MCs present in granulomatous tissues in accordance with the original hypothesis proposed by Facci et al. [19], or by the "entourage effect" operated by PEA on other endocannabinoid receptor targets, i.e. CB1 or TRPV1 receptors as previously demonstrated in a model of neuropathic pain by Costa et al. [32] or, finally, by the binding to an orphan receptor also expressed on mast cells, the G-protein coupled receptor-55 (GPR-55) [33]. This evidence concerns the gene GPR55 and Pain.