Involvement of spinal noradrenergic system in the mechanism of an antinociceptive effect of delta-sleep-inducing peptide (DSIP).

We studied whether the antinociceptive effect produced by intracerebroventricular injection of delta-sleep-inducing peptide (DSIP) to mice involved the monoaminergic pathways that descended from brainstem to spinal cord (the descending inhibitory systems). In the tail-pinch test, the antinociceptive effect of DSIP was significantly reduced by the pretreatment with reserpine (3 mg/kg i.p.) which depleted endogenous monoamines. Moreover, the intrathecal injections of monoamine antagonists were performed to evaluate the roles of the spinal noradrenergic and/or serotonergic systems in the production of the DSIP antinociception. In both tail-pinch and hot plate tests, the antinociceptive effect of DSIP was significantly antagonized by the previous intrathecal administration of phentolamine (an alpha-adrenergic blocker) or yohimbine (an alpha 2-adrenergic blocker), but was unaffected by the pretreatment with methysergide (a serotonin antagonist). These results demonstrate that the activation of the descending inhibitory systems, mainly spinal noradrenergic systems, is involved in the elicitation of DSIP antinociception.