α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic Acid Receptors Participate in the Analgesic but Not Hypnotic Effects of Emulsified Halogenated Anaesthetics

Hang, Li-Hua; Shao, Donghua; Yang, Yaojing; Sun, Wen-Jin; Ti-jun, Dai; Yin-ming, Zeng

doi:10.1111/j.1742-7843.2008.00270.x

Cited by 4 publications

(5 citation statements)

References 36 publications

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“…Previous studies support the efficacy and safety of the iv administration of emulsified inhalation anesthetics in animals [34,35]. According to drug pharmacokinetics and our preliminary experiments [6,7], we confirmed that ip and sc injection of emulsified inhalation anesthetics can achieve hypnosis and analgesia similar to that produced by inhalation. In the hypnosis test, hypnotic doses of emulsified sevoflurane induced the loss of mouse righting reflex.…”

Section: Discussionsupporting

confidence: 80%

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Involvement of 5-hydroxytryptamine type 3 receptors in sevoflurane-induced hypnotic and analgesic effects in mice

Hang

Shao

Wang

et al. 2010

Pharmacological Reports

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Abstract:In the present study, we investigated the role of 5-hydroxytryptamine type 3 (5-HT 3 ) receptors in hypnosis and analgesia induced by emulsified sevoflurane. A mouse model of hypnosis and analgesia was established by an intraperitoneal or subcutaneous injection of emulsified sevoflurane. We intracerebroventricularly (icv) or intrathecally (it) administered YM-31636, a 5-HT 3 receptor agonist, to mice and observed sleep time during hypnosis. In addition, the tail withdrawal latency was measured using the tail withdrawal test, and the writhing time was determined using the acetic acid writhing test. In the hypnosis test, YM-31636 (5, 10 and 15 µg, icv) treatment significantly decreased emulsified sevoflurane-induced mouse sleep time (p < 0.05 or p < 0.01). YM-31636 (2.5, 5 and 10 µg, it) treatment significantly and dose-dependently decreased the tail withdrawal latency (p < 0.05 or p < 0.01) and increased the writhing time (p < 0.01) of mice treated with emulsified sevoflurane. These results suggest that 5-HT 3 receptors may modulate the hypnotic and analgesic effects induced by emulsified sevoflurane.

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Section: Discussionsupporting

confidence: 80%

“…The hypnotic dose of sevoflurane (20 ml/kg) was determined in preliminary experiments [6]. Sevoflurane was injected intraperitoneally (ip) to produce hypnosis in mice.…”

Section: Drug Administrationmentioning

confidence: 99%

Involvement of 5-hydroxytryptamine type 3 receptors in sevoflurane-induced hypnotic and analgesic effects in mice

Hang

Shao

Wang

et al. 2010

Pharmacological Reports

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“…AMPA receptors contribute to the acute spinal processing of both nociceptive and non-nociceptive inputs in the spinal cord [23,24]. Not only have they been implicated in analgesic action of anaesthetics [25,26], but accumulating evidence indicates that they contribute to synaptic plasticity associated with chronic pain states [27,28]. There is still an ongoing controversy whether xenon inhibits AMPA receptors.…”

Section: Discussionmentioning

confidence: 99%

Xenon Inhibits Excitatory but Not Inhibitory Transmission in Rat Spinal Cord Dorsal Horn Neurons

et al. 2010

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BackgroundThe molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method.ResultsIn vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist.ConclusionsXenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon.

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“…There is also accumulating evidence of the importance of AMPA receptors in analgesic mechanisms associated with anaesthetic and non-anaesthetic drugs – such as xenon [27], halothane [28], and the AMPA antagonist Tezampel [29]. The amygdala is known to be associated with the emotional component of the pain experience [30, 31], and is linked with the paraventricular thalamus [32] in a circuit that modulates the endogenous descending anti-nociceptive pathways [33].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain

et al. 2019

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Background Ketamine ester analogs, SN 35210 and SN 35563, demonstrate different pharmacological profiles to ketamine in animal models. Both confer hypnosis with predictably rapid offset yet, paradoxically, SN35563 induces a prolonged anti-nociceptive state. To explore underlying mechanisms, broad transcriptome changes were measured and compared across four relevant target regions of the rat brain. Results SN 35563 produced large-scale alteration of gene expression in the Basolateral Amygdala (BLA) and Paraventricular Nucleus of the Thalamus (PVT), in excess of 10x that induced by ketamine and SN 35210. A smaller and quantitatively similar number of gene changes were observed in the Insula (INS) and Nucleus Accumbens (ACB) for all three agents. In the BLA and PVT, SN 35563 caused enrichment for gene pathways related to the function and structure of glutamatergic synapses in respect to: release of neurotransmitter, configuration of postsynaptic AMPA receptors, and the underlying cytoskeletal scaffolding and alignment. Conclusion The analgesic ketamine ester analog SN 35563 induces profound large-scale changes in gene expression in key pain-related brain regions reflecting its unique prolonged pharmacodynamic profile. Electronic supplementary material The online version of this article (10.1186/s12864-019-5649-6) contains supplementary material, which is available to authorized users.

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α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic Acid Receptors Participate in the Analgesic but Not Hypnotic Effects of Emulsified Halogenated Anaesthetics

Cited by 4 publications

References 36 publications

Involvement of 5-hydroxytryptamine type 3 receptors in sevoflurane-induced hypnotic and analgesic effects in mice

Involvement of 5-hydroxytryptamine type 3 receptors in sevoflurane-induced hypnotic and analgesic effects in mice

Xenon Inhibits Excitatory but Not Inhibitory Transmission in Rat Spinal Cord Dorsal Horn Neurons

Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain

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