Elsevier

Brain Research

Volume 460, Issue 2, 20 September 1988, Pages 281-296
Brain Research

Inhibition of spinal nociceptive transmission from the midbrain, pons and medulla in the rat: activation of descending inhibition by morphine, glutamate and electrical stimulation

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Abstract

It is generally believed that morphine activates a descending system(s) of inhibition, an effect contributing significantly to the analgesia produced. There has arisen, however, considerable controversy on this point. To address whether morphine inhibits spinal nociceptive transmission when given into the brainstem, the effects of focal electrical stimulation and monosodium S-glutamate (Glu) given in the periaqueductal gray (PAG), the locus coeruleus/subcoeruleus (LC/SC) and/or the nucleus raphe magnus (NRM) on spinal unit responses to noxious heating (50 °C) of the skin were examined and compared with effects produced by morphine (Mor). Focal electrical stimulation in 46 sites in the midbrain, dorsolateral pons and ventromedial medulla reliably inhibited unit responses to noxious heating of the skin (mean 34% of control). Microinjections of Glu (50 nmol, 0.5 μl) were made into 17 sites in the midbrain, 10 sites in the LC/SC and 11 sites in the NRM, inhibiting unit responses to a mean 57% at 22 of the 38 sites of microinjection. Mor (10–20 μg, 0.5 μl) was microinjected into 15 sites in the midbrain, 13 sites in the LC/SC and 11 sites in the NRM, inhibiting unit responses to heat to 63% of control at 24 sites of microinjection. The effects of morphine were shown to be receptor specific by antagonism with naloxone administered either intravenously or into the brainstem at the same site of microinjection as morphine. In 31 sites in the midbrain, dorsolateral pons and ventromedial medulla, microinjections of both Mor and Glu into the same sites attenuated unit responses to heating of the skin to a mean 77% and 71% of control, respectively. The results support the hypothesis that Mor acts supraspinally to modulate spinal nociceptive transmission by activating an endogenous descending inhibitory system(s). Focal electrical stimulation, glutamate and morphine modulated spinal nociceptive transmission by activation of descending inhibitory systems whose cell bodies of origin are in the PAG, the LC/SC or the NRM.

Reference (59)

  • JensenT.S. et al.

    II. Examination of spinal monoamine receptors through which brainstem opiate-sensitive systems act in the rat

    Brain Research

    (1986)
  • JonesS.L. et al.

    Characterization of coeruleospinal inhibition of the nociceptive tail-flick reflex in the rat: mediation by spinal α2 adrenoceptors

    Brain Research

    (1986)
  • KorfJ. et al.

    Noradrenergic neurons: morphine inhibition of spontaneous activity

    Eur. J. Pharmacol.

    (1974)
  • LeBarsD. et al.

    Microinjection of morphine within nucleus raphe magnus and dorsal horn neurone activities related to nociception in the rat

    Brain Research

    (1980)
  • LewisV.A. et al.

    Evaluation of the periaqueductal central gray (PAG) as a morphine-specific locus of action and examination of morphine-induced and stimulation-produced analgesia at coincident PAG loci

    Brain Research

    (1977)
  • LlewelynM.B. et al.

    Brainstem mechanisms of antinociception: effects of electrical stimulation and injection of morphine into the nucleus raphe magnus

    Neuropharmacology

    (1986)
  • MoreauJ.L. et al.

    Evidence for GABA involvement in midbrain control of medullary neurons that modulate nociceptive transmission

    Brain Research

    (1986)
  • NygrenL.G. et al.

    A new major projection from locus coeruleus: the main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord

    Brain Research

    (1977)
  • OssipovM.H. et al.

    Light pentobarbital anesthesia diminishes the antinociceptive potency of morphine administered intracranially but not intrathecally in the rat

    Eur. J. Pharmacol.

    (1984)
  • OssipovM.H. et al.

    Feline analgesia following central administration of opioids

    Neuropharmacology

    (1984)
  • PertA. et al.

    Sites of morphine induced analgesia in the primate brain: relation to pain pathways

    Brain Research

    (1974)
  • PubolsL.M. et al.

    Electrical stimulation reveals relatively ineffective sural nerve projections to dorsal horn neurons in the cat

    Brain Research

    (1986)
  • RandichA. et al.

    Interactions between cardiovascular and pain regulatory systems

    Neurosci. Biobehav. Rev.

    (1984)
  • RasmussenK. et al.

    Locus coeruleus unit activity in freely moving cats is increased following systemic morphine administration

    Brain Research

    (1985)
  • SegalM. et al.

    Analgesia produced by electrical stimulation of catecholamine nuclei in the rat brain

    Brain Research

    (1977)
  • SinclairJ.G.

    The failure of morphine to attenuate spinal cord nociceptive transmission through supraspinal actions in the cat

    Gen. Pharmacol.

    (1986)
  • TrulsonM.E. et al.

    Morphine increases locus coeruleus noradrenergic neuronal activity in vitro

    Eur. J. Pharmacol.

    (1986)
  • Van HarreveldA. et al.

    Light- and electron-microscopic changes in central nervous tissue after electrophoretic injections of glutamate

    Exp. Mol. Pathol.

    (1971)
  • VaskoM.R. et al.

    Involvement of 5-hydroxytryptamine-containing neurons in antinociception produced by injection of morphine into nucleus raphe magnus or onto spinal cord

    Brain Research

    (1984)
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    *

    Present address: Department of Physiology, University of North Carolina, Chapel Hill, NC 27514, U.S.A.

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