Morphine produces a biphasic modulation of substance P release from cultured dorsal root ganglion neurons

Abstract

We have previously reported that morphine produces a concentration-dependent multiphasic modulation (inhibitions and facilitations) of substance P (SP) release from trigeminal nucleus caudalis slices by activation of distinct populations of mu-, delta- and kappa-opioid receptors. In the present study, we have examined a wide range of morphine concentrations on K(+)-evoked SP release from dissociated rat dorsal root ganglion (DRG) neurons in culture. SP immunoreactivity was measured in the release buffer. Morphine produced a biphasic effect on K(+)-evoked SP release without affecting basal release. A concentration of 30 nM morphine facilitated SP release while a concentration of 1 microM suppressed release. Higher concentrations of morphine (10-30 microM) did not alter SP release. The facilitatory effect evoked by 30 nM morphine was abolished by opioid-receptor blockade with naloxone (30 nM) and the inhibitory effect produced by 1 microM morphine tended to be reversed. We conclude that an intact neuronal circuitry is not required for morphine to produce an opioid receptor mediated biphasic modulation of SP released from unmyelinated primary afferents. It is plausible that the dose-dependent biphasic effects of opioid agonists may also produce biphasic effects on nociception.