The aim of study was to examine the anti-inflammatory and
analgesic effects of
adelmidrol, an analogue of
palmitoylethanolamide (PEA), in animal models of acute and chronic
inflammation [
carrageenan-induced paw
edema (CAR) and
collagen-induced arthritis (CIA)]. In order to elucidate whether the action of
adelmidrol is related to activation of
peroxisome proliferator-activated receptors (
PPAR-α or
PPAR-γ), we investigated the effects of
PPAR-γ antagonist,
GW9662 on
adelmidrol mechanism. CAR induced paw
edema,
hyperalgesia and the activation of pro-inflammatory NF-κB pathway were markedly reduced by treatment with
adelmidrol.
GW9662, (administered prior to
adelmidrol treatment), antagonized the effect of
adelmidrol abolishing its positive action. On the contrary, the genetic absence of
PPAR-α receptor did not modify the beneficial results of
adelmidrol treatment in the acute model of
inflammation. In addition, for the first time, we demonstrated that
adelmidrol was able to ameliorate both the clinical signs and the histopathology of the joint and the hind paw during chronic
inflammation. In particular, the degree of oxidative damage and proinflammatory
cytokines and
chemokines production were significantly reduced in
adelmidrol-treated mice. Moreover, in CIA model, the effect of
GW9662 pre-treatment on
adelmidrol mechanism was also confirmed. Thus, in this study, we report that
adelmidrol reduces the development of acute and chronic
inflammation and could represent a novel therapeutic approach for
inflammation and
pain.