Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of GABA-ergic compounds on morphine-induced analgesia was studied to reveal probable interaction of GABA and opiates. As an index for morphine effect the reaction of vocalization in response to electrical stimulation of the rat tail was used. It was shown that thiosemicarbazide, the inhibitor of glutamate decarboxylase and bicuculline, GABA-ergic receptor blocking agent, which were proposed to be joined in a group of GABA-negative compounds, reduce and shorten the effect of morphine. Depakine, the inhibitor of alpha-ketoglutarate-GABA-transaminase, as well as GABA itself administered in high doses (GABA-positive actions) make morphine analgesia more pronounced and longer. Probable causes of the described interrelationship between GABA and opiates are discussed.
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PMID:[Effect of GABA-ergic substances on the analgesic effect of morphine in rats]. 38 Jun 85

Acute administration of morphine induced significant increases of gamma-amino-butyric acid (GABA) content and L-glutamate decarboxylase (GAD) activity at the dorsal parts of the dorsal horn and surroundings of the central canal in the rat spinal cord, in which GABA inhibitory interneurons may play significant roles. In the thalamus, morphine also induced significant increases of GABA content and GAD activity in the vicinity of the ventrolateral part of the ventral nucleus (VM), entopeduncular nucleus (EP), nucleus reuniens thalami (RE), nucleus parafascicularis thalami (PF) and interpeduncular nucleus (IP), respectively. The most significant increase of GABA was observed in the VM and PF, which are known to receive neuronal inputs from secondary neurons involved in the perception of pain. In spite of well-known involvement of periaqueductal gray matter (PVG) in the occurrence of morphine analgesia, GABA content in this area did not change following acute administration of morphine. The above mentioned increases of GABA in the spinal cord and thalamus were antagonized by the pretreatment with levallorphan, a narcotic antagonist, and were not observed when an analgesic dose of sodium salicylate or pentazocine was administered. On the other hand, acute administration of morphine failed to alter the microdistribution of taurine (2-aminoethanesulfonic acid) in the rat spinal cord and thalamus, in which significant increases of GABA content were observed. Contrary to the results obtained in acutely morphine-treated rats, animals rendered dependent by the implantation of a morphine pellet showed significant increases of taurine content in the spinal cord, whereas no change in GABA contents was detected in both spinal cord and thalamus. The present results suggest that morphine analgesia may involve mechanisms intensifying the inputs of GABA inhibitory neurons at the levels of the spinal cord and thalamus, where the primary and secondary neurons involved in the perception of pain are terminated respectively. Possible involvement of alterations in spinal taurine contents in the occurrence of morphine dependence are also suggested.
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PMID:Morphine induced alterations of gamma-aminobutyric acid and taurine contents and L-glutamate decarboxylase activity in rat spinal cord and thalamus: possible correlates with analgesic action of morphine. 56 49

Nucleus raphe magnus (NRM) sends the projection to spinal dorsal horn and inhibits nociceptive transmission. Analgesic effect produced by mu-opioid receptor agonists including morphine partially results from activating the NRM-spinal cord pathway. It is generally believed that mu-opioid receptor agonists disinhibit spinally projecting neurons of the NRM and produce analgesia by hyperpolarizing GABAergic interneurons. In the present study, whole-cell patch-clamp recordings combined with single-cell RT-PCR analysis were used to test the hypothesis that DAMGO ([D-Ala(2),N-methyl-Phe(4),Gly-ol(5)]enkephalin), a specific mu-opioid receptor agonist, selectively hyperpolarizes NRM neurons expressing mRNA of glutamate decarboxylase (GAD(67)). Homologous desensitization of mu-opioid receptors in NRM neurons could result in the development of morphine-induced tolerance. G protein-coupled receptor kinase (GRK) is believed to mediate mu-opioid receptor desensitization in vivo. Therefore, we also investigated the involvement of GRK in mediating homologous desensitization of DAMAMGO-induced electrophysiological effects on NRM neurons by using two experimental strategies. First, single-cell RT-PCR assay was used to study the expression of GRK2 and GRK3 mRNAs in individual DAMGO-responsive NRM neurons. Whole-cell recording was also performed with an internal solution containing the synthetic peptide, which corresponds to G(betagamma)-binding domain of GRK and inhibits G(betagamma) activation of GRK. Our results suggest that DAMGO selectively hyperpolarizes NRM GABAergic neurons by opening inwardly rectifying K(+) channels and that GRK2 mediates short-term homologous desensitization of mu-opioid receptors in NRM GABAergic neurons.
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PMID:G protein-coupled receptor kinase 2 mediates mu-opioid receptor desensitization in GABAergic neurons of the nucleus raphe magnus. 1129 6

Analgesic effects of serotonin (5-hydroxytryptamine [5-HT]) type 3 (5-HT3) receptors may involve the release of gamma-aminobutyric acid (GABA) in the spinal dorsal horn. However, the precise synaptic mechanisms for 5-HT3 receptor-mediated spinal analgesia are not clear. In this study, we investigated whether GABAergic neurons in the superficial dorsal horn (SDH) express functional 5-HT3 receptors and how these 5-HT3 receptors affect GABAergic inhibitory synaptic transmission in the SDH, by using slice preparations from adult glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mice. Tight-seal whole cell recordings from GFP-positive and -negative neurons showed that 5-HT3 receptor-specific agonist 2-methyl-serotonin (2-Me-5-HT) induced inward currents in a substantial population of both GFP-positive and -negative neurons. Additionally, we confirmed expression of 5-HT3 receptors in both types of neurons by single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis. Further, GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs)-both those evoked by electrical stimulation and those occurring spontaneously in tetrodotoxin (i.e., miniature IPSCs [mIPSCs])-were recorded from GFP-negative neurons. 2-Me-5-HT increased the amplitude of the evoked IPSCs and the frequency of mIPSCs. The amplitude of mIPSCs was not affected by 2-Me-5-HT, suggesting that 5-HT augments GABAergic synaptic transmission via presynaptic mechanisms. The present observations indicate that 5-HT3 receptors are expressed on both somadendritic regions and presynaptic terminals of GABAergic neurons and regulate GABAA receptor-mediated inhibitory synaptic transmission in the SDH. Taken together, these results provide clues for the underlying mechanisms of the antinociceptive actions of 5-HT3 receptors in the spinal dorsal horn.
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PMID:Facilitatory actions of serotonin type 3 receptors on GABAergic inhibitory synaptic transmission in the spinal superficial dorsal horn. 1936 58