Spinal nociceptive mechanisms: Mu- but Not Delta- Opioid Receptor activation depresses nociceptive transmission in the isolated spinal cord of neonatal rats

Abstract

The roles and functions of opioid receptors, especially delta-receptors in mediating nociceptive transmission in infant animals are not clear. The present study was designed to investigate the involvements of delta- and mu-opioid receptors in spinal nociceptive transmission in the neonatal rat. Immature rats (7-14 days old) of either sex were deeply anaesthetized with urethane. Hemisected spinal cords with attached dorsal and ventral roots were isolated and perfused continuously with artificial cerebrospinal fluid at room temperature. Dorsal root evoked-population ventral root potentials (DR-VRP) in the ventral root were recorded in response to supermaximal electrical stimulation of the corresponding dorsal root (segments L4-5). Supermaximal electrical shock to a dorsal root evoked a typical DR-VRP, consisting of an initial monosynaptic compound action potential of motoneurones (MSP) superimposed on a population excitatory postsynaptic potential (e.p.s.p.) followed by a prolonged population e.p.s.p. , which lasts for tens of seconds. Bath perfusion of SNC-80, a highly selective non-peptide delta-opioid receptor agonist, at 1(n=2), 10 (n=8) and 100 (n=3) mM did not depress the DR-VRP. In contrast, DAMGO, a highly selective mu-receptor agonist, dose-dependently (3, 10, 30, 100 nM) depressed the nociceptive reflex activity. At 100 nM (n=4), the evoked long during DR-VRPs were depressed by 59 + 4% (area under the curve) of pre-drug control. Steady state depression was reached at 10-15 min following DAMGO perfusion and the depressant effect was reversed by washout. Unlike mu-opioid receptors, the present data indicate that delta-opioid receptors are not actively involved in spinal nociceptive related reflex activity in the immature rat.