Developmental Brain Research, 41 (1988) 109-120 109 Elsevier BRD 50762 Analgesic effects of intrathecally applied noradrenergic compounds in the developing rat: differences due to thermal vs mechanical nociception Harry E. Hughes and Gordon A. Barr Biopsychology Doctoral Program, Department of Psychology, Hunter College and the City University of New York, New York, NY10021 (U.S.A.)and Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY10461 (U.S.A.) (Accepted 12 January 1988) Key words: Development; Analgesia; Intrathecal; Receptor type; Noradrenaline; Clonidine; Noxious stimulus; Spinal cord 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, lntra- thecal norepinephrine resulted in analgesia that was more pronounced against a mechanical than thermal stimulus and more pro- nounced in 10-day-olds than 3-day-olds. The ct 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 clo- nidine was also greatest at 10 days of age. The cq 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. INTRODUCTION Various lines of evidence suggest that inhibition of spinal dorsal horn activity and behaviorally defined analgesia are under descending noradrenergic con- trol. Dorsal horn nociceptive neurons were inhibited following iontophoretically applied norepinephrine (NE) 3'2° while intrathecally applied NE produced a dose-dependent behavioral analgesia against a ther- mally noxious stimulus 3°'31. Analgesia and dimin- ished activity of dorsal horn neurons followed electri- cal stimulation of the ventromedial medullary retic- ular formation. This effect was blocked by tetrabena- zine, a NE depleter, and was reestablished with L- DOPA, a NE precursor 1'37. It has been demonstrated that electrical stimula- tion of central and peripheral pain related loci such as the magnocellular tegmentum, dorsolateral funiculus or sciatic nerve cause release of NE in the spinal cord 39"42. Stimulation of the nucleus raphe magnus also increased the effiux of NE into superfusates of the spinal cord 18. Systemic morphine 34 and microin- jection of morphine into the nucleus reticularis para- gigantoceilularis 25 increased the concentration of the NE metabolite normetanephrine in the spinal cord. Recent anatomic evidence suggests that cells that re- lease NE to produce their antinociceptive effects de- scend to the spinal cord from supraspinal sites. Im- munohistochemistry has shown that somata contain- ing NE were located most caudally in cell groups at the upper cervical region of the spinal axis 2s. These cervical neurons most likely represent a caudal ex- tension of noradrenergic nuclei from the medulla. Therefore, the antinociceptive effects of intrathecal- ly applied NE agonists are mediated by NE contain- ing cells not intrinsic to the spinal cord. Correspondence." G.A. Barr, Department of Psychiatry, Room G49C, Albert Einstein College of Medicine, 1300 Morris Park Ave- nue, Bronx, NY 10461, U.S.A. 0165-3806/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)