Electrophysiological studies on the postnatal development of the spinal antinociceptive effects of the delta opioid receptor agonist DPDPE in the rat

1 The antinociceptive effects of the delta opioid receptor selective agonis t, DPDPE [(D-Pen(2),D-Pen(5))-enkephalin] was studied in rats aged postnata l day (P) 14, P21, P28 and P56. 2 Antinociceptive effects of DPDPE were measured as percentage inhibition o f the C-fibre evoked response and post-discharge of dorsal horn neurones ev oked by peripheral electrical stimulation. DPDPE was administered by topica l application, akin to intrathecal injection. 3 DPDPE (0.1-100 mu g) produced dose-related inhibitions at all ages; these inhibitions were reversed by 5 mu g of the opioid antagonist naloxone. 4 The dose-response curves for C-fibre evoked response and post-discharge o f the neurones were not different in rats aged P14 and P21. DPDPE was signi ficantly more potent at P14 and P21 compared with its inhibitory effects on these responses at P28 and P56. 5 DPDPE produced minor inhibitions of the A-fibre evoked response of the ne urones at P14, P21, P28 and P56, suggesting that the inhibitory effects of DPDPE are mediated via presynaptic receptors on the terminals of C-fibre af ferents. 6 Since spinal delta opioid receptor density changes little over this perio d, the increased antinociceptive potency of DPDPE in the rat pups compared with the adult is likely to be due to post-receptor events, or in developme ntal changes in the actions of other transmitter/receptor systems within th e spinal cord.