Analgesic effects of intraventricular and intrathecal injection of morphine and ketocyclazocine in the infant rat

Little is known of the neural bases of analgesia in immature animals. This experiment examined the effects of intracerebroventricular (i.c.v.) and intrathecal (i.t.) administration of morphine or ketocyclazocine in tests of antinociception in rats aged 3 to 14 days of age. Analgesia tests were conducted using both thermal and mechanical (pressure) noxious stimuli applied to the forepaw, hindpaw or tail. In the 3-day-old morphine-injected i.c.v. produced analgesia in the forepaws when either the mechanical or thermal noxious stimulus was used. There was no effect when the hindpaw or tail was tested. At 10 days of age, when the mechanical stimulus was used, morphine was analgesic in tests on all three appendages but was only effective in the forepaw when the thermal stimulus was used. Morphine was fully effective in all tests with both stimuli at 14 days of age. Ketocyclazocine had no consistent effect when given i.c.v. When injected i.t., morphine produced analgesia in the forepaws in the thermal test at 4 days of age and in all appendages by 10 days. When the mechanical test was used, morphine was effective in all appendages at all ages tested. Ketocyclazocine was analgesic at all appendages for the mechanical stimulus at all ages but was only transiently effective in the thermal test. The results demonstrate differential development of analgesia mediated at different levels of the neural axis and are consistent with the development of descending inhibitory that may mediate analgesia induced by i.c.v. injections of morphine. Neural mechanisms that are involved in the analgesic effects of these drugs against the two types of stimuli are also developmentally distinct.