Analgesic effects of intrathecally applied noradrenergic compounds in the developing rat: differences due to thermal...

Peak noradrenergic receptor development in rat spinal cord has been shown to occur around 12 days of postnatal life. The intent of the present study was to examine the development of analgesia produced by spinally applied noradrenergic agonists. The extent to which these drugs modulate pain information evoked by a thermal vs mechanical stimulus in the infant rat was also addressed. Intrathecal norepinephrine resulted in analgesia that was more pronounced against a mechanical than thermal stimulus and more pronounced in 10-day-olds than 3-day-olds. The alpha 2 receptor agonist clonidine produced a dose-dependent analgesia that first appeared at 7 days of age when tested with a thermal stimulus and 3 days of age when tested with a mechanical stimulus. The analgesic effect of clonidine was also greatest at 10 days of age. The alpha 1 agonist phenylephrine was without analgesic effects. The developmental profile of behavioral analgesia correlates with the ontogeny of noradrenergic receptor activity in the spinal cord. The finding that intrathecal norepinephrine produced a more pronounced analgesia against a mechanical rather than thermal stimulus in the adult is supported by our investigation in the infant rat.