Brain research
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Fluorescence immunohistochemistry was used to analyze the medulla oblongata of colchicine-treated rats that had been incubated with guinea pig antibodies to serotonin (5-HT) and either rabbit or sheep antibodies to glutamic acid decarboxylase (GAD). Numerous cells in the rostral ventrolateral medulla in the region of nucleus raphe magnus were immunostained for either 5-HT or GAD. ⋯ In addition, a number of the 5-HT/GAD-containing neurons were retrogradely labelled with Fast blue dye that had been injected into the thoracic spinal cord. This work provides evidence for colocalization of the classical neurotransmitters 5-HT and GABA in single cells of the ventral medulla oblongata, some of which project to the spinal cord.
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Clonidine and morphine depress nociceptive reflex responses when given alone; when given in combination, the effect of each is potentiated by the other. The present study was designed to test if activity in ascending axons evoked by electrical stimulation of afferent C-fibers in the sural nerve of the rat also exhibits potentiation of the depressant effects of clonidine and morphine when both drugs are administered in combination by intrathecal (i.t.) injection to the lumbar spinal cord. For comparison, experiments were also carried out on the tail-flick response in rats. ⋯ The dose-response curve of depression by morphine alone of C-fiber-evoked activity (ED50 8 micrograms) is significantly shifted by clonidine to the left (ED50 0.9 microgram). Naloxone (0.2 mg/kg) injected intravenously did not affect the inhibition of ascending activity caused by clonidine at the highest dose (35 micrograms), but it reduced the depressant effect of combined i.t. administration of clonidine and morphine. The potentiation of the antinociceptive effects of clonidine and morphine given in combination are possibly due to actions of the two drugs at different sites between the nociceptive afferents and the neurons sending their axons to the brain.
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Extracellular and intracellular recordings were made from within the dorsal horn of 10 anaesthetised and gallamine triethiodide-paralysed cats. Inhibition of background and residual noxious-evoked discharge by cooling and warming was demonstrated in 7 out of 33 nociceptor-driven dorsal horn neurones. Five units were inhibited by warming of the noxious mechanical excitatory receptive field. ⋯ Cooling (32-20 degrees C) excited two units; warming (32-43 degrees C) also excited two units. Heating above 43 degrees C excited 8 units; cold below 20 degrees C excited 3 units. The units inhibited by thermal stimulation may provide some neuronal basis for thermal analgesia.
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The lateral reticular nucleus (LRN) and locus coeruleus-subcoeruleus (LC/SC), brainstem structures which overlap the A1 and A6 noradrenergic nuclei respectively, have been implicated in descending modulation of spinal nociceptive transmission. The present studies were designed to examine the role of norepinephrine (NE) in the mediation of inhibition of the nociceptive tail flick reflex produced by focal electrical stimulation in the LRN and LC/SC. Spinal NE was depleted by intrathecal administration of 6-hydroxydopamine (6-OHDA; 20 micrograms) and the threshold electrical stimulation in the LRN and the LC/SC necessary to inhibit the tail flick reflex in lightly pentobarbital-anesthetized rats was determined 9 and 14 days later. ⋯ Binding of [3H]rauwolscine to lumbar spinal cord revealed an elevation in the estimated Bmax without a change in the estimated Kd of the high affinity binding component 9 days following 6-OHDA administration. This study demonstrates that spinal adrenoceptor denervation supersensitivity develops rapidly following intrathecal administration of 6-OHDA and compensates for the selective destruction of spinal noradrenergic nerve terminals. Thus, the absence of effect of NE depletion on the tail flick inhibitory stimulation threshold in the LRN and the LC/SC does not argue against the hypothesis that spinopetal NE-containing neurons in these brainstem loci are involved in modulation of spinal nociceptive transmission.
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Centrifugal modulation from the midbrain, pons and medulla of the spinal nociceptive tail flick (TF) reflex evoked by graded noxious heating of the tail was studied in lightly pentobarbital-anaesthetized rats. In initial experiments, the relationship between the intensity of the noxious thermal stimulus and the TF latency was characterized. The thermal stimulus was provided by a lamp focused on the ventral surface of a rat's tail. ⋯ Type II modulations were produced by electrical stimulation in the dorsolateral pons, locus coeruleus-subcoeruleus and in the medial periaqueductal gray. This experimental approach has shown itself to be useful in the characterization of descending inhibition of nociception. Much simpler and less invasive than analogous spinal dorsal horn single cell electrophysiologic studies, it can be used to study the mechanisms of centrifugal modulation of nociceptive flexion reflexes and further establishes the utility of the lightly anaesthetized rat preparation for studies of nociception-antinociception.