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 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 a specific
kappa opioid receptor agonist, U50,488 (trans-(1S,2S)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide hydrochloride hydrate), administered into the temporomandibular joint decreases
formalin-induced plasma extravasation and neutrophil migration. Ipsilateral, but not contralateral, administration of U50,488 into the temporomandibular joint blocked
formalin-induced plasma extravasation and neutrophil migration in a dose-dependent manner. This anti-inflammatory effect was reversed by the ipsilateral, but not contralateral, administration of the
kappa 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 potent antinociceptive effect, suggests 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.