POSTNATAL-DEVELOPMENT OF MULTIPLE OPIOID RECEPTORS IN THE SPINAL-CORDAND DEVELOPMENT OF SPINAL MORPHINE ANALGESIA

The postnatal ontogeny of mu, delta and kappa opioid receptor binding sites in the spinal cord of rat pups at various postnatal days was det ermined using in vitro autoradiographical methods. The functional effe ct of spinal morphine was also assessed using in vivo electrophysiolog ical methods in rats at P14, P21 and adults (P56). Both mu and kappa o pioid receptor binding-sites are present from PO and spread relatively diffusely throughout the spinal cord. Overall binding peaks at P7 and subsequently decreases to adult levels with the mu opioid receptor bi nding sites regressing to become denser in the superficial dorsal horn . delta Opioid receptor binding was first seen at P7, and no distincti on between superficial and deeper laminae was seen. In the adult, the relative proportions of the opiate receptors in the superficial dorsal horn are 63%, 22% and 15%, for mu, delta and kappa receptor binding s ites, respectively. C-fibre evoked dorsal horn neuronal responses reco rded from anaesthetized rat pups were highly sensitive to spinal morph ine at P21, (EC50 0.005 mu g), compared to the adult (EC50 0.9 mu g). However, the EC50 (0.2 mu g) at P14 was greater than at P21 despite th e fact that mu receptor binding was greater at P14. Opioid receptor bi nding is developmentally regulated and undergoes substantial postnatal reorganization. However, the number of mu receptor binding sites appe ars not to be the only determinant of functional sensitivity to spinal morphine. Other factors, such as coupling of the receptors are likely to be important. (C) 1998 Elsevier Science B.V. Ail rights reserved.