The effects of glutamate (Glu), gamma-aminobutyric acid (GABA), glycine (Gly), serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh) were examined in this study by iontophoretic application onto primate spinothalamic tract (STT) neurons identified antidromically by stimulation in the contralateral thalamus. Drugs were tested for effects on background activity, Glu-induced firing, and activity evoked by pinching of the skin. Whereas Glu excited STT cells and was thus used for tests of the other compounds, the amino acids GABA and Gly inhibited Glu- and pinch-induced activity in all STT cells examined. STT cells were also inhibited by 5-HT, NE, and DA. Only two cases of excitation by 5-HT were seen (of 58 cells tested). ACh also had inhibitory actions on STT cells, although 3 of 21 cells exhibited some enhancement of activity. The effects of these compounds on identified STT cells resemble previous demonstrations of the effects of these drugs on dorsal horn interneurons. The results suggest that GABA, Gly, 5-HT, NE, and DA may be inhibitory neurotransmitters on nociceptive STT cells.
The effects of iontophoretically applied opiates were tested on 24 spinothalamic tract cells in 12 anesthetized monkeys. The drugs used were chosen because of their agonist actions on different classes of opiate receptors (mu, morphine; kappa, dynorphin; delta, methionine enkephalinamide; sigma, N-allylnormetazocine or SKF 10047 and phencyclidine). The actions of the opiate drugs were generally inhibitory, although excitatory or mixed effects were sometimes seen, especially with morphine and dynorphin. Drug effects could change, depending on the position of the iontophoretic electrode array or on the current employed. Naloxone sometimes antagonized the action of the opiate drugs used, but naloxone did not seem to be a drug suited for iontophoretic application. A number of explanations are discussed to explain the variable actions of the opiate drugs.
The peptides substance P (SP), methionine-enkephalin (M-ENK), leucine-enkephalin (L-ENK), and cholecystokinin (CCK) were released iontophoretically near spinothalamic tract (STT) cells in anesthetized monkeys and STT-like cells in decorticate, spinalized monkeys. Peptide effects were observed on background discharges, firing induced by release of glutamate, and activity evoked by pinching the skin. SP could have any of several actions on STT cells, including excitation, inhibition, or biphasic effects. Multiple effects often resulted while recording from an individual cell when the dose or the electrode position was changed. M-ENK and L-ENK generally inhibited STT cells, and in some cases it was possible to demonstrate a reversal of the inhibition by naloxone. CCK also caused an inhibition that was additive with that produced by L-ENK. The multiple actions of SP on STT cells suggests the possibility that there may be more than one type of SP receptor on STT cells, although alternative explanations should be considered. Inhibition of STT cells by M- and L-ENK is consistent with the known analgesic action of opiates through spinal cord mechanisms. CCK has an action on STT cells similar to that of the enkephalins.
Recordings were made from 132 raphe- and reticulospinal tract neurons in the medial part of the lower brain stem in 32 anesthetized monkeys. Recording sites were in the nucleus raphe magnus, the rostral nucleus raphe obscurus, and the reticular formation adjacent to the raphe. The neurons were identified by antidromic activation from the upper lumbar spinal cord. Of the population sampled, 83 cells were activated antidromically from the left dorsal lateral funiculus (DLF), 32 from the right DLF, and 17 from both sides. The mean latency for antidromic activation was 8.2 +/- 7.1 ms, corresponding to a mean conduction velocity of 22.8 m/s. No conduction velocities characteristic of unmyelinated axons were observed. Collision tests indicated that raphe-spinal axons that bifurcated to descend in both DLFs branched within the spinal cord. The effects of stimulation in the periaqueductal gray (PAG) or adjacent midbrain reticular formation were tested on 102 spinally projecting neurons in the medial medulla. Of these, 60 cells were excited, 9 cells were inhibited, 8 showed mixed excitation and inhibition, and 25 cells were unaffected. The mean latency for excitation was 11.6 ms and for inhibition, 17.8 ms. Threshold for excitation of raphe- and reticulospinal neurons ranged from 50 to 400 microA. Raphe- and reticulospinal tract cells could often (31/46 cells tested) be excited following stimulation in the ventral posterior lateral nucleus of the thalamus. The mean latency of excitation was 35.6 ms (range, 6-112 ms). Receptive fields could be demonstrated for 80 raphe- and reticulospinal cells, while 48 neurons possessed no demonstrable cutaneous receptive field. Most cells had large excitatory receptive fields, often encompassing the surface of the entire body and face. Some neurons had complex excitatory and inhibitory receptive fields, whereas other cells had large inhibitory receptive fields over much of the surface of the body and face. For most cells (52/55) with excitatory receptive fields, the only effective stimuli were noxious mechanical or noxious heat stimuli. Nonnoxious mechanical stimuli, such as brushing the skin, were capable of activating only a few (3/55) raphe- and reticulospinal neurons, and these were more effectively excited by noxious stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)
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