Postnatal development of multiple opioid receptors in the spinal cord and 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 determined using in vitro autoradiographical methods. The functional effect of spinal morphine was also assessed using in vivo electrophysiological methods in rats at P14, P21 and adults (P56). Both mu and kappa opioid receptor binding-sites are present from P0 and spread relatively diffusely throughout the spinal cord. Overall binding peaks at P7 and subsequently decreases to adult levels with the mu opioid receptor binding sites regressing to become denser in the superficial dorsal horn. delta Opioid receptor binding was first seen at P7, and no distinction 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 sites, respectively. C-fibre evoked dorsal horn neuronal responses recorded from anaesthetized rat pups were highly sensitive to spinal morphine at P21, (EC50 0.005 microgram), compared to the adult (EC50 0.9 microgram). However, the EC50 (0.2 microgram) at P14 was greater than at P21 despite the fact that mu receptor binding was greater at P14. Opioid receptor binding is developmentally regulated and undergoes substantial postnatal reorganization. However, the number of mu receptor binding sites appears 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.
Dept. of Pharmacology, University College London, UK.
W
W
Rahman
M R
MR
Dashwood
M
M
Fitzgerald
A
A
Aynsley-Green
A H
AH
Dickenson
D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D044482:Benzeneacetamides; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009412:Nerve Fibers / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists / Q000032:analysis*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000032:analysis; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000032:analysis; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000032:analysis; D013116:Spinal Cord / Q000737:chemistry* / Q000187:drug effects* / Q000254:growth & development
D000700:Analgesics; D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593