The pharmaco-ontogeny of spinal noradrenergic receptor systems mediating behavioral analgesia in the rat.
Item
-
Title
-
The pharmaco-ontogeny of spinal noradrenergic receptor systems mediating behavioral analgesia in the rat.
-
Identifier
-
AAI8914760
-
identifier
-
8914760
-
Creator
-
Hughes, Harry Edward.
-
Contributor
-
Adviser: Gordon A. Barr
-
Date
-
1988
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Psychology, Psychobiology
-
Abstract
-
Behaviorally defined analgesia as measured by different pain assessment tests has been demonstrated to be under descending noradrenergic control. Peak noradrenergic receptor development in rat spinal cord occurs around 12 days of postnatal life. The first part of this thesis examined 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 produced analgesia that was more pronounced against a mechanical than thermal stimulus and more pronounced in 10 day olds than 3 days olds. The {dollar}\alpha\sb2{dollar} 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 peak analgesic effect of clonidine occurred at 10 days of age. In contrast, the {dollar}\alpha\sb1{dollar} agonist phenylephrine was without analgesic effects. This 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. The second part of this thesis examined the characteristics of opioid-noradrenergic interactions in modulating pain responses in the developing rat. Intrathecal injection of the {dollar}\alpha{dollar}-antagonist phentolamine decreased analgesia produced by intraventricular morphine for a mechanical but not thermal stimulus. No difference between 3 and 10 day olds was observed in this effect. In contrast, phentolamine did not alter response latencies elevated by intrathecal morphine. The pharmacologic profile which characterizes opioid-noradrenergic systems for pain modulation in adult rats appears to be established early in development.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
