May 1, 1985

Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing

Pharmacology, Biochemistry, and Behavior
T L Yaksh

Abstract

Spinopetal pathways may be activated by a variety of brainstem manipulations including microinjections of morphine which are known to modulate spinal nociceptive processing. Based on the ability of these manipulations to release spinal noradrenalin; the ability to reverse the antinociceptive effects by intrathecal adrenergic antagonists and the fact that intrathecal injections of noradrenalin mimic the antinociceptive effect, it appears that the descending modulation may be mediated by descending noradrenergic systems. Examination of the spinal receptor systems with intrathecally administered agents indicates that spinal alpha, but not beta adrenergic receptor agonists produce a powerful analgesia as measured on a variety of reflex and operant measures in mouse, rat, cat, primate and man. On the basis of agonist and antagonist structure-activity relationships it appears that a significant effect can be produced in the absence of any detectable effect on motor function by the occupation of spinal alpha 2 receptors. Distinguishable alpha 1 receptors also appear "analgetically-coupled," but their effects are uniformly contaminated by signs of cutaneous hyperreflexia at doses required to produce analgesia. The ordering of potency w...Continue Reading

Mentioned in this Paper

Biochemical Pathway
Entire Brainstem
Structure-Activity Relationship
Morphine Measurement
Tachyphylaxis
Drug Tolerance
Antagonist Muscle Action
Adrenergic Agonists
Absence of Pain Sensation
Adrenergic beta-Agonists

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