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      Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing

      Pharmacology Biochemistry and Behavior
      Elsevier BV

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          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 with which intrathecal adrenergic antagonists reverse the effects of intrathecal noradrenalin is indistinguishable from that of the reversal by these intrathecal agents of the antinociceptive effects evoked by brainstem morphine. This suggests that the population of spinal receptors acted upon by exogenously administered adrenergic agonists and endogenously released noradrenaline have indistinguishable characteristics.

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          Author and article information

          Journal
          Pharmacology Biochemistry and Behavior
          Pharmacology Biochemistry and Behavior
          Elsevier BV
          00913057
          May 1985
          May 1985
          : 22
          : 5
          : 845-858
          Article
          10.1016/0091-3057(85)90537-4
          2861606
          6cea6a8b-6b31-4384-85a2-936926b50d8f
          © 1985

          https://www.elsevier.com/tdm/userlicense/1.0/

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