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Title: The developmental neurobiology of opioids
Author: Nandi, L. Reema S. N.
ISNI:       0000 0001 3439 427X
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2004
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Opioid analgesia is widely used in neonates. There is evidence that morphine requirements may be low in the youngest patients. Opioid receptors are developmentally regulated, but there are no studies of opioid receptor function in the immature sensory nervous system. The aim of this MD was to determine (i) postnatal changes in opioid receptor distribution and function in rat sensory neurons (ii) whether alterations in morphine efficacy, consistent with changing opioid receptor function, occur over the postnatal period. Methods: Mu opioid receptor (MOR) immunostaining combined with selective neurofilament labelling to distinguish large A fibres from small C dorsal root ganglion (DRG) neurons was used to study the postnatal regulation of MOR across these two subpopulations of sensory neurons in cultured rat DRG cells. Calcium imaging was used to examine MOR function using the same model. In order to determine whether changing functional MOR expression with increasing age has an effect on the intact nervous system, behavioural sensory thresholds measurements to mechanical and noxious thermal tests were conducted in neonatal and young adult rats following morphine administration. Dose response curves of morphine potency in sensory tests over the postnatal period were generated from these tests. Results: Calcium imaging showed that significantly more functional mu opioid receptors are expressed in neonatal DRG neurons compared to adult. This over expression is confined to the large, A sensory neurons, while expression in small, C neurons remains unchanged. In behavioural tests, dose response curves demonstrated that the analgesic potency of morphine to mechanical cutaneous sensory stimulation is significantly greater in the neonate and declines with postnatal age. This was not observed in thermal nociceptive tests. Conclusion: Functional MOR are more widely expressed in the neonatal DRG, particularly on large A neurons. These MOR are subject to postnatal developmental regulation. This changing functional receptor profile is consistent with greater morphine potency in mechanical sensory tests in young animals. These results have important clinical implications for the use of morphine in neonates and provide a possible explanation for the differences in morphine requirements observed in the youngest patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available