Postnatal development of multiple opioid receptors in the spinal cord and development of spinal morphine analgesia

• Published in: Brain research. Developmental brain research Vol. 108; no. 1; pp. 239 - 254
• Main Authors: Rahman, W., Dashwood, M.R., Fitzgerald, M., Aynsley-Green, A., Dickenson, A.H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.1998
• Subjects: Analgesics - pharmacology; Analgesics, Opioid - pharmacology; Animals; Autoradiography; Benzeneacetamides; Development; Dose-Response Relationship, Drug; Electrophysiology; Enkephalin, Ala-MePhe-Gly; Enkephalin, D-Penicillamine (2,5); Enkephalins - pharmacology; Male; Morphine; Morphine - pharmacology; Nerve Fibers - chemistry; Nerve Fibers - drug effects; Nerve Fibers - physiology; Opioid receptor; Pyrrolidines - pharmacology; Radioligand Assay; Rat; Rats; Rats, Sprague-Dawley; Receptors, Opioid - agonists; Receptors, Opioid - analysis; Receptors, Opioid, delta - agonists; Receptors, Opioid, delta - analysis; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - analysis; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - analysis; Spinal cord; Spinal Cord - chemistry; Spinal Cord - drug effects; Spinal Cord - growth & development; Autoradiography; Spinal cord; Rat; Opioid receptor; Development; Electrophysiology; Morphine
• ISSN: 0165-3806
• DOI: 10.1016/S0165-3806(98)00054-6

The postnatal ontogeny of μ, δ and κ 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 μ and κ 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 μ opioid receptor binding sites regressing to become denser in the superficial dorsal horn. δ 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 μ, δ and κ receptor binding sites, respectively. C-fibre evoked dorsal horn neuronal responses recorded from anaesthetized rat pups were highly sensitive to spinal morphine at P21, (EC 50 0.005 μg), compared to the adult (EC 50 0.9 μg). However, the EC 50 (0.2 μg) at P14 was greater than at P21 despite the fact that μ receptor binding was greater at P14. Opioid receptor binding is developmentally regulated and undergoes substantial postnatal reorganization. However, the number of μ 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.