Efeito da ativação local do receptor capa opióide no extravasamento plasmático e migração de neutrófilos na articulação temporomandibular de ratos / Effect of local activation of opioid kappa receptors in plasma extravasation and neutrophil migration in the temporomandibular joint in rats

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

29/07/2011

RESUMO

In an attempt to decrease central side effects associated with the use of opioids, some strategies have been developed by targeting peripheral opioid receptors. In this context, kappa opioid receptors are of major interest, since, in contrast to other opioid receptors, their activation is not associated with potent peripheral side effects. We have recently demonstrated that local activation of kappa opioid receptors significantly decreases formalin-induced temporomandibular joint nociception, however, whether it also decreases temporomandibular joint inflammation is not known. To address this issue, we evaluated if the selective kappa opioid receptor agonist, U50,488 (trans-(1S,2S)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] enzeneacetamide hydrochloride hydrate), administered into the temporomandibular joint decreases formalin-induced plasma extravasation and neutrophil migration. The intensity of plasma extravasation was determined by measuring the concentration of Evan´s blue dye extravasated in the articular tissue and the intensity of leukocyte migration was determined by measuring Myeloperoxidase activity also in the articular tissue. Data were analyzed by ANOVA and Tukey post hoc test (p?0.05) and the results are expressed as mean ± EPM. The co-administration of 1.5% formalin with the selective kappa opiod receptor agonist U50,488 at 50 ?g significantly reduced the plasma extravasation (Mean±EPM: 23.42 ?g/g ± 4.88) compared to the other groups receiving 1.5% formalin plus U50,488 at 1.5?g (46.60 ?g/g ± 5,40) and at 30?g (37.60 ?g/g ± 3.64). When applied on the contralateral temporomandibular joint, U50,488 had no effect on formalin-induced plasma extravasation. The co-administration of 1.5% formalin with U50,488 at 1.5?g significantly reduced formalin-induced neutrophil migration (1.10 ?g/mg ±0.20) compared to the other groups receiving 1.5% formalin plus U50,488 at 0.3?g (3.23?g/mg ± 0.56) and at 0.75?g (2.43 ?g/mg ± 0.42). When applied on the contralateral temporomandibular joint, U50,488 had no effect on formalin-induced neutrophil migration. The anti-inflammatory effect of U50,488 was blocked by the ipsilateral, but not contralateral administration of the selective kapa opioid receptor antagonist nor-BNI (Nor-Binaltorphimine dihydrochloride). This study demonstrates that local activation of kappa opioid receptors decreases two important parameters of temporomandibular joint inflammation, that is, plasma extravasation and neutrophil migration, in a dose-dependent and antagonist-reversible manner. This anti-inflammatory effect taken together with the previously demonstrated potent antinociceptive effect of U50,488, suggest that drugs targeting peripheral kappa opioid receptors are promising for the treatment of inflammatory temporomandibular joint pain and probably, other articular pain conditions with an inflammatory basis

ASSUNTO(S)

boca - fisiologia inflamação mecanismos de reação orgânica oral fisiology inflammation organic reaction mechanisms

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