Epidural opioid analgesia in infant rats - I: mechanical and heat responses

The aim of this study was to investigate the analgesic effects of epidural opioids in neonatal rat pups. The contribution of individual opioid recepto r subtypes in the spinal cord to analgesia at different developmental stage s was investigated using epidural mu (morphine sulphate), delta (DPDPE) and kappa (U69593) opioid receptor agonists in neonatal rats aged postnatal da y (P) 3, 10 and 21. Thresholds for flexion withdrawal reflexes to mechanica l stimuli (von Frey hairs) and to noxious heating of the hind paw were low in neonates and increased with postnatal age. The analgesic action of each opioid receptor agonist followed an individual developmental pattern. In me chanical tests, all three opioid agonists were considerably more efficaciou s analgesics in younger animals and ED50s at P3 were always lower than at P 21. In heat tests, the pattern differed. The efficacy of the kappa opioid a gonist decreased with postnatal age, morphine efficacy increased over the s ame period and the effects of the delta agonist remained relatively unchang ed. The distribution and concentration of tritiated morphine in the spinal cord following epidural administration did not alter significantly with pos tnatal age, suggesting that opioid access is not a major determinant of the effects reported here. It is concluded that whereas heat pain is particula rly sensitive to spinal kappa opioids in neonates, mechanical sensory thres holds are generally sensitive to all spinal opioids in the newborn. The dif fering epidural opioid requirements compared to older subjects is likely to be due to developmental changes in spinal cord opioid receptor distributio n or pharmacology. (C) 1999 International Association for the Study of Pain . Published by Elsevier Science B.V.