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Development of opioid analgesic systems in the rat

Rahman, Wahida; (1999) Development of opioid analgesic systems in the rat. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The neonatal central nervous system proceeds through a number of functional stages before reaching maturity. Since spinal opioid receptors play a major role in the modulation of nociception this thesis examines aspects of their development. Using immunohistochemical methods, with antisera to μ, δ and receptors and in vitro autoradiography with tritiated ligands for μ, δ and κ receptors, the postnatal distribution and density of spinal opioid receptors was investigated. Both μ and kappa opioid receptor binding-sites are present from postnatal day (P) 0, but δ opioid receptor binding was first seen at P7. All three receptors are subject to postnatal modifications in density and localization over the first three weeks. Extracellular recordings were made from dorsal horn neurones receiving input from both A and C-fibre afferents in anaesthetized rats at P14, P21, P28 and P56 (adult). The inhibitory effects of spinal morphine and DPDPE on the evoked neuronal responses were determined. The potencies of morphine and DPDPE were significantly greater in the rat pups compared to adults; no correlation with the density of the receptors in the spinal cord was seen. After administration of morphine at P1 the potency of spinal morphine in the adult rat was decreased. This shift in the dose-response curve was not due to changes in the density of mu receptors in the spinal cord, but changes in endogenous cholecystokinin could be involved. Inflammatory hyperalgesia at P1, either alone or in the presence of an effective dose of morphine, did not produce any changes in the neuropharmacology of adult spinal opioid systems. These studies add to knowledge of the physiology and pharmacology of spinal opioid analgesia. They support the practice of adequate opioid therapy in early life but suggest that inappropriate administration of morphine can produce detrimental enduring changes.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Development of opioid analgesic systems in the rat
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Opioid receptors
URI: https://discovery.ucl.ac.uk/id/eprint/10103502
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