Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of iontophoretic applications of 5-hydroxytryptamine (5-HT) were tested upon primate spinothalamic tract neurons recorded extracellularly in the spinal cord of anesthetized monkeys. The activity of most high threshold and wide dynamic range spinothalamic tract cells was depressed. 5-HT also reduced the responses of the cells to glutamate pulses which by themselves had a powerful excitatory action. It is concluded that 5-HT has a depressant action upon the postsynaptic membranes of spinothalamic tract cells, although the action has a slow time course. The observations are consistent with, but by no means prove, the hypothesis that serotonergic pathways descending from the brain stem produce a postsynaptic inhibiton of spinothalamic tract neurons.
Pain 1978 Aug
PMID:Depression of primate spinothalamic tract neurons by iontophoretic application of 5-hydroxytryptamine. 9 15

Extra- and intracellular recordings were obtained from physiologically identified, spinal neurones in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. Microiontophoretically applied methionine- and leucine-enkephalin reversibly inhibited the spontaneous, synaptically induced, and L-glutamate-induced activity in the majority of dorsal horn neurones studied in laminae 4, 5 and 6 of Rexed. Most of these depressant effects were antagonized by the prior microiontophoretic application of the opiate antagonist naloxone. Intracellular studies performed on dorsal horn neurones and motoneurones revealed that microiontophoretically applied methionine- and leucine-enkephalin caused no change in the resting membrane potential or the membrane resistance. Neither spike initiation nor spike overshoot were detectably altered by either enkephalin. The membrane depolarization and associated decrease in membrane resistance following microiontophoretic L-glutamate application were effectively blocked by the prior application of enkephalin. Naloxone, which by itself had no detectable effect on the membrane resistance, antagonized this effect. We propose that [enkephalinergic] cells in lamina II and III may modulate cells subserving somatosensory perception, including pain.
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PMID:The effects of methionine- and leucine-enkephalin on spinal neurones of the cat. 22 94

Substantial differences have been found in the plastic reorganizations of neuronal activity of the rat sensorimotor cortex at local and systemic reinforcements. In nineteen (95%) out of 20 neurones stable and one-type changes of response to CS (electrical stimulation of the cortex) developed in the course of pairings with local ionophoretic application of L-glutamate in the vicinity of the studied neurone. Twenty two units were studied during the pairings of electrical stimulation of the cortex with pain electrocutaneous stimulation: plastic reorganizations in response to CS were revealed only in eight (36.4%) units; they were, however, of long duration and were more diverse in pattern, than in the series with local reinforcement. It is assumed that different plastic reorganizations in these two model situations of learning depend on the number and reactive properties of the participating units.
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PMID:[Plastic transformation of the activity of cortical neurons upon pairing a signal stimulus with microiontophoresis or electrocutaneous stimulation]. 69 36

Experiments were performed to evaluate the effects on the levels of aspartate, GABA and glutamate in the periaqueductal central gray matter, hypothalamus, midbrain reticular formation and cortex of mouse brain following various treatments. The results indicate that only glutamate among the 3 neurohumors is systematically altered relative to the experimental manipulations. Moreover, among the 4 brain areas examined, the data implicate only the periaqueductal central gray matter as a locus of morphine's antinociceptive action. Morphine also appears to produce a drug-specific effect in hypothalamus which, however, is not analgesia-related. There were no significant pain, stress or drug-related effects on the levels of glutamate in either the midbrain reticular formation or the cortex.
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PMID:Morphine and pain: effects on aspartate, GABA and glutamate in four discrete areas of mouse brain. 93 43

Experiments were performed to determine 1) whether synergism existed between morphine and gamma-hydroxybutyrate in the production of analgesia and 2) the effect of each of these agents on pain-induced changes in brain amino acid content in mice. The analgetic ED50 for both agents was determined using hot plate and tail-flick procedures. The combination of one-half the ED50 of each agent produced an effect equivalent to the ED50 of either agent administered alone in the hot plate but not in the tail-flick test. Although both agents produced an unresponsiveness to noxious stimulation, only morphine prevented pain-induced alterations in brain GABA and glutamate levels.
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PMID:An evaluation of the analgesia induced by morphine gamma-hydroxybutyrate. 114 17

Recent advances in the molecular biology of excitatory amino acid receptors are reviewed. Evidence that drugs blocking the excitatory action of glutamate at the N-methyl-D-aspartate (NMDA) and non-NMDA receptors may be of clinical use in epilepsy, Parkinson's disease, cerebral ischaemia and trauma, acquired immune deficiency syndrome (AIDS) encephalopathy and neuropathic pain is summarized.
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PMID:Excitatory amino acid receptors and disease. 132 24

In awake, freely moving rats, the intracerebral administration of the excitatory amino acid L-glutamate (30 nmol/0.5 microliters) into discrete regions of the brainstem resulted in a transient and spontaneous pain-like syndrome characterized by an initial vocalization and vigorous escape behavior. Systematic microinjection mapping studies were carried out at sites distributed caudally from the lower medulla and rostrally into diencephalon. These studies revealed that the spontaneous pain-like behavior was observed to occur after glutamate injection in 13% of 331 microinjected sites, and these sensitive sites were largely limited to the mesencephalic periaqueductal gray matter. The behavioral syndrome was dose-dependent and antagonized in a dose-dependent fashion by the glutamate receptor antagonists MK 801 and DL-2-amino-5 phosphonovalerate but not by gamma-D-glutamyl-amino-methylsulfonic acid. The pain-like behavior was also produced by the other excitatory amino acid receptor agonists N-methyl-D-aspartate, quisqualate and to a certain extent by kainate in a dose-dependent manner with the order of potency being N-methyl-D-aspartate = kainate greater than quisqualate greater than D-glutamate. The effects of N-methyl-D-aspartate and quisqualate were antagonized by MK 801 and DL-2-amino-5 phosphonovalerate but not by gamma-D-glutamyl-amino-methylsulfonic acid. It is suggested that the pain-like behavioral syndrome is the result of focal occupation of N-methyl-D-aspartate receptors on neuronal populations in the terminal regions of rostrally projecting spinomesencephalic systems.
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PMID:Brainstem excitatory amino acid receptors in nociception: microinjection mapping and pharmacological characterization of glutamate-sensitive sites in the brainstem associated with algogenic behavior. 134 50

The roles of N-methyl-D-aspartate (NMDA) receptors and protein kinase C (PKC) are critical in generating and maintaining a variety of sustained neuronal responses. In the nociceptive (pain-sensing) system, tissue injury or repetitive stimulation of small-diameter afferent fibres triggers a dramatic increase in discharge (wind-up) or prolonged depolarization of spinal cord neurons. This central sensitization can neither be induced nor maintained when NMDA receptor channels are blocked. In the trigeminal subnucleus caudalis (a centre for processing nociceptive information from the orofacial areas), a mu-opioid receptor agonist causes a sustained increase in NMDA-activated currents by activating intracellular PKC. There is also evidence that PKC enhances NMDA-receptor-mediated glutamate responses and regulates long-term potentiation of synaptic transmission. Despite the importance of NMDA-receptors and PKC, the mechanism by which PKC alters the NMDA response has remained unclear. Here we examine the actions of intracellularly applied PKC on NMDA-activated currents in isolated trigeminal neurons. We find that PKC potentiates the NMDA response by increasing the probability of channel openings and by reducing the voltage-dependent Mg2+ block of NMDA-receptor channels.
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PMID:Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. 137 27

The effects of an experimentally induced arthritis on immunoreactivity of putative primary afferents neurotransmitter/neuromodulators were examined. Immunoreactive staining for substance P (SP), calcitonin gene-related peptide (CGRP) and glutamate (Glu) in the monkey dorsal horn was examined following inflammation of one knee joint induced by injection of 5% kaolin and 5% carrageenan. Spinal cords were examined at different time periods after induction of arthritis (2.5, 4, 6 and 8 h). Side to side differences in immunoreactivity were determined by a computer assisted quantitation system. A significant overall decrease in immunoreactivity of the lumbar versus the cervical dorsal horn was found for SP. The decrease for SP showed maximal changes of 68.3% at 4 h and 54.7% at 6 h. Immunoreactivity for CGRP was decreased 31.5% at 8 h and variable at other time points. Immunoreactivity for Glu, showed an ipsilateral increase of 31.4% at 4 h, 33.7% at 6 h, 39.9% at 8 h and a significant effect for lumbar versus cervical. Repetitive peripheral stimulation of the joint was shown to be important for changes in SP and Glu immunoreactivity. Without frequent peripheral stimulation in the early stages of the development of arthritis, SP showed no quantitative side to side differences. Increases in Glu immunoreactivity were present but not as prominent with minimal joint manipulation. These studies suggest that Glu may be involved in the aching pain of inflammation at rest whereas SP, CGRP and Glu may mediate pain induced by joint movement.
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PMID:Neural changes in acute arthritis in monkeys. III. Changes in substance P, calcitonin gene-related peptide and glutamate in the dorsal horn of the spinal cord. 137 98

Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in the periphery is commonly accepted as the primary mechanism by which these agents produce a selective attenuation of pain (analgesia). NSAIDs are now shown to exert a direct spinal action by blocking the excessive sensitivity to pain (hyperalgesia) induced by the activation of spinal glutamate and substance P receptors. These findings demonstrate that the analgesic effects of NSAIDs can be dissociated from their anti-inflammatory actions. Spinal prostanoids are thus critical for the augmented processing of pain information at the spinal level.
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PMID:Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. 138 21


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