The differential effect of morphine and β-endorphin administered intracerebroventricularly on pERK and pCaMK-II expression induced by various nociceptive stimuli in mice brains

The present study was performed to characterize the differential molecular mechanisms of morphine and β-endorphin which are injected intracerebroventiricularly in mice. In the immunoblot assay, the increases of phosphorylated extracellular signal-regulated protein kinase (pERK) as well as phosphorylated calcium/calmodulin-dependent protein kinase IIα (pCaMK-IIα) expression induced by noxious stimuli were attenuated by intracerebroventricular (i.c.v.) β-endorphin pretreatment in the hypothalamus, but not by i.c.v. morphine pretreatment. In addition to these immunoblot results, immunohistochemical study also showed that the attenuation of pERK or pCaMK-IIα immunoreactivity elicited by i.c.v. pretreatment of β-endorphin mainly occurred in the paraventricular nucleus of the hypothalamus (PVN). We also investigated the effect of morphine and β-endorphin on pERK and pCaMK-IIα expression in the locus coeruleus (LC). I.c.v. injection of morphine significantly increased pERK as well as pCaMK-IIα expression in the locus coeruleus, while β-endorphin increased only pCaMK-IIα in the LC. In addition, β-endorphin significantly attenuated pERK expression induced by SP i.t. injection. These results suggest that the antinociceptive effects of supraspinally administered morphine and β-endorphin are involved with differentially intracellular signal transduction molecules-pERK, pCaMK-IIα in the PVN and the LC.