GABAB receptor-mediated presynaptic inhibition of glycinergic transmission onto substantia gelatinosa neurons in the rat spinal cord

Choi, In Sun; Cho, Jin Hwa; Jeong, Seok Gwon; Hong, Jung Soo; Sang-Jeong, Kim; Kim, Jun; Lee, Maan‐Gee; Choi, Byung Ju; Jang, Il‐Sung

doi:10.1016/j.pain.2008.01.005

Cited by 14 publications

(7 citation statements)

References 44 publications

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“…Taurine is another agonist at this receptor with perhaps even higher efficacy than glycine in neurons of spinal cord lamina II (592). At glycinergic synapses in superficial spinal dorsal horn, release of glycine may be inhibited by presynaptic GABA B receptors (70).…”

Section: Glycinergic Systemsmentioning

confidence: 99%

Models and Mechanisms of Hyperalgesia and Allodynia

Sandkühler¹

2009

Physiological Reviews

992

753

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Hyperalgesia and allodynia are frequent symptoms of disease and may be useful adaptations to protect vulnerable tissues. Both may, however, also emerge as diseases in their own right. Considerable progress has been made in developing clinically relevant animal models for identifying the most significant underlying mechanisms. This review deals with experimental models that are currently used to measure (sect. II) or to induce (sect. III) hyperalgesia and allodynia in animals. Induction and expression of hyperalgesia and allodynia are context sensitive. This is discussed in section IV. Neuronal and nonneuronal cell populations have been identified that are indispensable for the induction and/or the expression of hyperalgesia and allodynia as summarized in section V. This review focuses on highly topical spinal mechanisms of hyperalgesia and allodynia including intrinsic and synaptic plasticity, the modulation of inhibitory control (sect. VI), and neuroimmune interactions (sect. VII). The scientific use of language improves also in the field of pain research. Refined definitions of some technical terms including the new definitions of hyperalgesia and allodynia by the International Association for the Study of Pain are illustrated and annotated in section I.

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Section: Glycinergic Systemsmentioning

confidence: 99%

Models and Mechanisms of Hyperalgesia and Allodynia

Sandkühler¹

2009

Physiological Reviews

992

753

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“…One proposed mechanism is enhanced glycinergic inhibition to compensate reduced GABAergic inhibition in the spinal cord. Because spinal interneurons seem to corelease both GABA and glycine to activate functionally distinct receptors in their postsynaptic target cells (Jonas et al, 1998), reduced GABAergic transmission in GAD65(Ϫ/Ϫ) mice may produce enhanced glycinergic inhibition via reduced presynaptic tonic inhibition mediated by GABA B receptors (Choi et al, 2008). If so, it is possible that relatively small reduction in GABAergic inhibition does not affect net inhibitory tone in the spinal cord.…”

Section: Downloaded Frommentioning

confidence: 99%

Thermal Hyperalgesia via Supraspinal Mechanisms in Mice Lacking Glutamate Decarboxylase 65

Kubo

Nishikawa²,

Ishizeki³

et al. 2009

J Pharmacol Exp Ther

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␥-Aminobutyric acid, which is synthesized by two isoforms of glutamate decarboxylase (GAD), inhibits the transfer of nociceptive signals from primary afferent fibers to the central nervous system. However, the roles of a 65-kDa isoform of GAD (GAD65)-mediated GABA in nociceptive processing are less clear. This study tested whether partial reductions in GABAergic inhibitory tone by GAD65 gene knockout [GAD65(Ϫ/Ϫ)] would contribute to the regulation of pain threshold in mice. Experiments were performed on male wild-type (WT) mice and GAD65(Ϫ/Ϫ) mice. Acute nociception and inflammatory pain tests were compared between WT mice and GAD65(Ϫ/Ϫ) mice. GABA A receptor-mediated inhibitory postsynaptic currents were also examined by use of the whole-cell patch-clamp method in somatosensory cortical neurons in brain slices. In the hot plate test, which reflects supraspinal sensory integration, a significant reduction in the latency was observed for GAD65(Ϫ/Ϫ) mice. Intraperitoneal administration of the GABAethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (C 21 H 22 N 2 O 3 ⅐HCl; NO-711), dose-dependently prolonged the latency in both genotypes, suggesting that GABA concentration contributes to acute thermal nociception. However, there was no genotype difference in responses to the tailimmersion test or the von Frey test, indicating that spinal reflex and mechanical nociception are kept intact in GAD65(Ϫ/Ϫ) mice. There was no genotype difference in responses to chemical inflammatory nociception (formalin test and carrageenan test). Although properties of the phasic component of inhibitory postsynaptic currents were similar in both genotypes, tonic inhibition was significantly reduced in GAD65(Ϫ/Ϫ) mice. These results support the hypothesis that GAD65-mediated GABA synthesis plays relatively small but significant roles in nociceptive processing via supraspinal mechanisms.

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“…Forskolin elicits a long-lasting increase in glycinergic IPSCs in immature SG neurons In spinal cord slices bathed in 3 mM kynurenic acid, which blocks ionotropic glutamate receptors (Stone and Burton 1988), electrical field stimulation adjacent to lamina II evoked a fast outward synaptic current in SG neurons held at a holding potential of 0 mV. The outward current was completely blocked by cumulative application of both 10 lM SR95531, a selective GABA A receptor antagonist, and 1 lM strychnine, a glycine receptor antagonist (data not shown), indicating that the recorded outward current was a mixture of GABAergic and glycinergic IPSCs (see also Choi et al 2008). In order to investigate whether cAMP modulates action potential-dependent glycinergic synaptic transmission on to SG neurons, all the following experiments were performed in the presence of 10 lM SR95531, and glycinergic IPSCs were evoked by pairing stimulation at an interval of 100 ms (10 Hz).…”

Section: Resultsmentioning

confidence: 81%

“…In spinal cord slices bathed in 3 mM kynurenic acid, which blocks ionotropic glutamate receptors (Stone and Burton 1988), electrical field stimulation adjacent to lamina II evoked a fast outward synaptic current in SG neurons held at a holding potential of 0 mV. The outward current was completely blocked by cumulative application of both 10 μM SR95531, a selective GABA A receptor antagonist, and 1 μM strychnine, a glycine receptor antagonist (data not shown), indicating that the recorded outward current was a mixture of GABAergic and glycinergic IPSCs (see also Choi et al. 2008).…”

Section: Resultsmentioning

confidence: 87%

Cyclic AMP‐mediated long‐term facilitation of glycinergic transmission in developing spinal dorsal horn neurons

Choi

Nakamura

Cho

et al. 2009

Journal of Neurochemistry

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cAMP is known to regulate neurotransmitter release via protein kinase A (PKA)-dependent and/or PKA-independent signal transduction pathways at a variety of central synapses. Here we report the cAMP-mediated long-lasting enhancement of glycinergic transmission in developing rat spinal substantia gelatinosa neurons. Forskolin, an adenylyl cyclase activator, elicited a long-lasting increase in the amplitude of nerve-evoked glycinergic inhibitory postsynaptic currents (IPSCs), accompanied by a long-lasting decrease in the paired-pulse ratio in immature substantia gelatinosa neurons, and this forskolin-induced increase in glycinergic IPSCs decreased with postnatal development. Forskolin also decreased the failure rate of glycinergic IPSCs evoked by minimal stimulation, and increased the frequency of glycinergic miniature IPSCs. All of these data suggest that forskolin induces the long-lasting enhancement of glycinergic transmission by increasing in the presynaptic release probability. This pre-synaptic action of forskolin was mediated by hyperpolarization and cyclic nucleotide-activated cation channels and an increase in intraterminal Ca(2+) concentration but independent of PKA. The present results suggest that cAMP-dependent signal transduction pathways represent a dynamic mechanism by which glycinergic IPSCs could potentially be modulated during postnatal development.

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GABAB receptor-mediated presynaptic inhibition of glycinergic transmission onto substantia gelatinosa neurons in the rat spinal cord

Cited by 14 publications

References 44 publications

Models and Mechanisms of Hyperalgesia and Allodynia

Models and Mechanisms of Hyperalgesia and Allodynia

Thermal Hyperalgesia via Supraspinal Mechanisms in Mice Lacking Glutamate Decarboxylase 65

Cyclic AMP‐mediated long‐term facilitation of glycinergic transmission in developing spinal dorsal horn neurons

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