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Stimulation-produced descending inhibition from the lateral hypothalamus: neuronal pathways and neurotransmitters
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COERULEOSPINAL INHIBITION OF NOCICEPTIVE TRANSMISSION IN THE RAT. S.L. Jones and G.F. Gebhart, Dept. of Pharmacology,I i;;;;;;;; 3 1 Univ. of Iowa, Iowa City, Iowa, 52242, USA. Aims: This study 1) systematically examined inhibition of the tail-flick (TF) reflex produced by stimulation in the locus coeruleus/subcoeruleus (LC/SC) and determined the spinal neurotransmitter(s) mediating that inhibition, and 2) characterized electrophysiologically inhibition of heat-evoked (50°C) dorsal horn neuronal responses from the LC/SC and pathways in the brainstem and spinal cord mediating that inhibition. Methods: TF studies utilized the lightly pentobarbital-anesthetized rat. Pharmacologic antagonists were administered intrathecally. Electrophysiologic studies were done in deeply-anesthetized rats. Neuronal transmission was interrupted reversibly and irreversibly with lidocaine microinjections into the medulla and spinal cord and by transections of the dorsolateral funiculi, respectively. Results: Sites in the dorsolateral pons requiring the lowest intensities to inhibit the TF were in the LC/SC; the inhibition results from the activation of cell bodies in the LC/SC and is mediated by spinal postsynaptic a -adrenoceptors. LC/SC stimulation-producedinhibition of heatevoked un1t activity is intensity-, pulse duration-, and frequencydependent; stimulation in the LC/SC modulates the gain of unit responses to graded noxious heating. Nucleus raphe magnus bulbospinal neurons do not contribute to descending inhibitory influences from the LIZ/SC. Coeruleospinal fibers exerting inhibitory influences on heat-evoked activity project to the lumbar spinal cord in the ipsilateral ventrolateral quadrant of the cervical spinal cord. Conclusions: A direct coeruleospinalprojection can be activated which modulates nociceptive withdrawal reflexes and nociceptive transmission.
STIMULATION-PRODUCEDDESCENDING INHIBITION FROM THE LATERAL HYPOTHALAMUS: NEURONAL PATHWAYS AND NEUROTRANSMITTERS. L.D. Aimone and G.F. Gebhart, Department of Pharmacology, Board 24 University of Iowa. Iowa City. IA 52242. USA Aim of-investigation: This study was-undertaken to characterize stimulation-produced descending inhibition from the lateral hypothalamus (LH), including an examination of the neuronal pathway(s) and the spinal neurotransmitter(s)mediating the descending inhibition. Methods: Inhibition of the tail flick (TF) reflex in rats lightly anesthetized with pentobarbital was studied. Systematic electrode tracking, intracerebral microinjections and intrathecal administration of selective pharmacologic antagonists were employed. Results: Systematic electrode tracking demonstrated that inhibition of the nociceptive TF reflex could be produced throughout the hypothalamus, with the most effective sites located in the Ill. Activation of fibers of passage through this area was responsible for inhibition of the TF reflex. Intrathecal administration of pharmacologic antagonists revealed that the a-adrenoceptor antagonists yohimbine and phentolamine produced the greatest increases in stimulation thresholds in the LH for inhibition of the TF reflex. Methysergide, a serotonergic antagonist, also produced a small but statistically significant increase in the stimulation threshold for inhibition of the TF reflex. Reversible and/or selective intracerebral lesions demonstrated that fibers of passage through the dorsolateral pons and cell bodies in the rostroventral medulla are involved in descending inhibition from the LH. Conclusions: These results clearly demonstrate a contribution from the lateral hypothalamus to endogenous systems of descending inhibition of Supported by DA 02879 and T32 GM 07069. nociceptive transmission.
COERULEOSPINAL INHIBITION OF NOCICEPTIVE TRANSMISSION IN THE RAT. S.L. Jones and G.F. Gebhart, Dept. of Pharmacology,I i;;;;;;;; 3 1 Univ. of Iowa, Iowa City, Iowa, 52242, USA. Aims: This study 1) systematically examined inhibition of the tail-flick (TF) reflex produced by stimulation in the locus coeruleus/subcoeruleus (LC/SC) and determined the spinal neurotransmitter(s) mediating that inhibition, and 2) characterized electrophysiologically inhibition of heat-evoked (50°C) dorsal horn neuronal responses from the LC/SC and pathways in the brainstem and spinal cord mediating that inhibition. Methods: TF studies utilized the lightly pentobarbital-anesthetized rat. Pharmacologic antagonists were administered intrathecally. Electrophysiologic studies were done in deeply-anesthetized rats. Neuronal transmission was interrupted reversibly and irreversibly with lidocaine microinjections into the medulla and spinal cord and by transections of the dorsolateral funiculi, respectively. Results: Sites in the dorsolateral pons requiring the lowest intensities to inhibit the TF were in the LC/SC; the inhibition results from the activation of cell bodies in the LC/SC and is mediated by spinal postsynaptic a -adrenoceptors. LC/SC stimulation-producedinhibition of heatevoked un1t activity is intensity-, pulse duration-, and frequencydependent; stimulation in the LC/SC modulates the gain of unit responses to graded noxious heating. Nucleus raphe magnus bulbospinal neurons do not contribute to descending inhibitory influences from the LIZ/SC. Coeruleospinal fibers exerting inhibitory influences on heat-evoked activity project to the lumbar spinal cord in the ipsilateral ventrolateral quadrant of the cervical spinal cord. Conclusions: A direct coeruleospinalprojection can be activated which modulates nociceptive withdrawal reflexes and nociceptive transmission.
STIMULATION-PRODUCEDDESCENDING INHIBITION FROM THE LATERAL HYPOTHALAMUS: NEURONAL PATHWAYS AND NEUROTRANSMITTERS. L.D. Aimone and G.F. Gebhart, Department of Pharmacology, Board 24 University of Iowa. Iowa City. IA 52242. USA Aim of-investigation: This study was-undertaken to characterize stimulation-produced descending inhibition from the lateral hypothalamus (LH), including an examination of the neuronal pathway(s) and the spinal neurotransmitter(s)mediating the descending inhibition. Methods: Inhibition of the tail flick (TF) reflex in rats lightly anesthetized with pentobarbital was studied. Systematic electrode tracking, intracerebral microinjections and intrathecal administration of selective pharmacologic antagonists were employed. Results: Systematic electrode tracking demonstrated that inhibition of the nociceptive TF reflex could be produced throughout the hypothalamus, with the most effective sites located in the Ill. Activation of fibers of passage through this area was responsible for inhibition of the TF reflex. Intrathecal administration of pharmacologic antagonists revealed that the a-adrenoceptor antagonists yohimbine and phentolamine produced the greatest increases in stimulation thresholds in the LH for inhibition of the TF reflex. Methysergide, a serotonergic antagonist, also produced a small but statistically significant increase in the stimulation threshold for inhibition of the TF reflex. Reversible and/or selective intracerebral lesions demonstrated that fibers of passage through the dorsolateral pons and cell bodies in the rostroventral medulla are involved in descending inhibition from the LH. Conclusions: These results clearly demonstrate a contribution from the lateral hypothalamus to endogenous systems of descending inhibition of Supported by DA 02879 and T32 GM 07069. nociceptive transmission.