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

Abstract

The present study was designed to investigate the role of α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hypnosis and analgesia induced by emulsified inhalation anaesthetics. After having established the mice model of hypnosis and analgesia by intraperitoneally injecting appropriate doses of emulsified enflurane, isoflurane or sevoflurane, we intracerebroventricularly or intrathecally injected different doses of AMPA and then observed the effects on the sleep time using hypnosis test and the tail-withdrawal latency using the tail-withdrawal test. In hypnosis test, AMPA (50, 75 and 100 ng, intracerebroventricularly) had no distinctive effects on the sleep time of the mice treated with emulsified inhalation anaesthetics (P > 0.05). In tail-withdrawal test, AMPA (0.25, 0.5 and 1.0 ng, intrathecally) significantly and dose-dependently decreased the tail-withdrawal latency (P < 0.05 or P < 0.01) in the mice treated with emulsified anaesthetics. These results suggest that AMPA receptors may participate in the analgesic but not in the hypnotic effects induced by emulsified enflurane, isoflurane or sevoflurane.

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

“…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.…”

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

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

“…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.…”

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

“…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].…”