Halothane Antagonizes Effect of Morphine on the Motor Reaction Threshold in Rats

Kissin, Igor; Jebeles, John A.

doi:10.1097/00000542-198412000-00008

Cited by 15 publications

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“…Antagonism between nitrous oxide and volatile anaesthetics has also been reported for MAC in the rat [8,14] and suppression of learning in humans [15], although interpretation of the MAC studies is a subject of much debate [16][17][18]. Similarly, a marked morphine-halothane antagonism has been reported for the escape reaction threshold to tail pressure [19] and the cardiac acceleration response to tail clamp [20] in the rat, but the agents were additive in suppressing noxious stimulation-induced purposeful movements [20]. Thus the nature of these drug interactions may vary with the end-point.…”

Section: Discussionmentioning

confidence: 91%

“…Second, the tail-flick response is a spinal reflex [4] and such measures are not used clinically to evaluate the adequacy of anaesthesia, analgesia, or both. Third, as discussed previously, the nature of the interaction among anaesthetics appears to vary for different end-points [1,8,14,19,20]; integrated, complex pain processes may be affected differently than a spinal reflex. Nevertheless, our experiments demonstrate that a simple relationship between anaesthesia and analgesia cannot be assumed because addition of a volatile anaesthetic to nitrous oxide or morphine, while deepening anaesthesia, resulted in less profound analgesia.…”

Section: Discussionmentioning

confidence: 92%

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Volatile anaesthetics antagonize nitrous oxide and morphine-induced analgesia in the rat

Goto

Marota

Crosby

1996

British Journal of Anaesthesia

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We reported previously that nitrous oxide induces pre-emptive analgesia that is partially antagonized by naloxone and totally antagonized by halothane. The aims of this study were to determine if halothane and isoflurane are similar in this respect and to examine if volatile anaesthetics antagonize the analgesic effect of exogenous opioids. We found that 75% nitrous oxide prolonged tail-flick latency by 37% and this analgesia was dose-dependently inhibited by halothane and, less effectively, by isoflurane. In contrast, morphine 1.25 mg kg-1 i.v. also prolonged tail-flick latency by 35% but, unlike nitrous oxide-induced analgesia, this effect was attenuated only by high doses of halothane and was unaffected by isoflurane. Neither halothane nor isoflurane alone altered the tail-flick response. We conclude that both halothane and isoflurane dose-dependently antagonized nitrous oxide analgesia but antagonized morphine-induced analgesia to a lesser extent.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 92%

Volatile anaesthetics antagonize nitrous oxide and morphine-induced analgesia in the rat

Goto

Marota

Crosby

1996

British Journal of Anaesthesia

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“…Immobility: Experiments on movement response to noxious stimulation showed results similar to those reported in humans: opioids reduced the MAC of inhaled anesthetics (Supplemental Digital Content, http://links.lww.com/AA/E570). 31–42…”

Section: Resultsmentioning

confidence: 99%

Antinociceptive Agents as General Anesthetic Adjuncts: Supra-additive and Infra-additive Interactions

Kissin

2023

Anesthesia &Amp; Analgesia

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The hypothesis “General anesthesia consists of producing both loss of consciousness and the inhibition of noxious stimuli reaching the brain and causing arousal” was used as a basis for the review of published data on general anesthetic interactions with antinociceptive agents: opioids, α2 adrenergic agonists, and systemic sodium channel blockers. This review is focused on a specific type of anesthetic interaction—the transformation of antinociceptive agents into general anesthetic adjuncts. The primary aim is to answer 2 questions. First, how does an antinociceptive agent transform the effect of an anesthetic in providing a certain component of anesthesia—hypnosis, immobility, or hemodynamic response to noxious stimulation? Second, does a combination of an anesthetic with an adjunct result in a simple summation of their respective effects or in a supra-additive or infra-additive interaction? The Medline database was searched for data describing the interactions of antinociceptive agents and general anesthetics. The following classes of antinociceptive agents were considered: opioids, α2 adrenergic agonists, and systemic sodium channel blockers. Drugs used in combination with antinociceptive agents were general anesthetics and benzodiazepines. The following terms related to drug interactions were used: anesthetic interactions, synergy, antagonism, isobolographic analysis, response surface analysis, and fractional analysis. The interactions of antinociceptive agents with general anesthetics result in a decrease of general anesthetic requirements, which differ for each of the components of general anesthesia: hypnosis, immobility, and hemodynamic response to noxious stimulation. Most studies of the nature of anesthetic interactions are related to opioid–general anesthetic combinations, and their conclusions usually confirm supra-additivity.

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“…[21][22][23][24] Other studies have shown that halogenated anesthetics induce hyperalgesia when administered at very low concentrations 25,26 and even decrease morphine analgesic effects. 25,27 However, in the context of current clinical practice, it is unresolved as to whether or not inhaled anesthetics elicit residual effects on postoperative hyperalgesia. To address this issue, we undertook a study to evaluate whether or not sevoflurane can antagonize fentanyl-induced hyperalgesia in rats, with or without inflammatory pain.…”

Section: Résumémentioning

confidence: 99%

Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats

Richebé

Rivalan

Rivat

et al. 2008

Can J Anesth/J Can Anesth

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Purpose Opioids are widely used for anesthesia but paradoxically induce postoperative pain hypersensitivity via N-methyl-D-aspartate (NMDA) receptor modulation. Sevoflurane effects on opioid-induced hyperalgesia have not been yet evaluated in vivo. Nevertheless, some experimental in vitro studies reported anti-NMDA receptor properties for sevoflurane. The aim of this study was to evaluate sevoflurane effects on fentanyl-induced hyperalgesia in opioid-naive rats and in rats with inflammatory pain. Methods Sevoflurane effects on hyperalgesia were evaluated in Sprague-Dawley rats: opioid-naive rats, rats treated with fentanyl (4 9 60 lg kg -1 ) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 9 60 lg kg -1 ). On day zero, subcutaneous fentanyl injections were administered and inflammatory pain was induced with one carrageenan injection in one hind paw. Rats were exposed to low concentrations of sevoflurane (1.0 or 1.5%) on day zero prior to fentanyl injections and inflammatory pain induction, and for the duration of the fentanyl analgesic effect. The nociceptive threshold (Randall-Selitto test) was evaluated daily for 7 days. On day seven, naloxone was injected and the nociceptive threshold was assessed 5 min later. Results In rats without inflammatory pain but treated with fentanyl on day zero, sevoflurane 1.0% reversed the early (day zero) and long-lasting (day zero to day three) hyperalgesia classically described after high-doses of fentanyl (P \ 0.05). This sevoflurane concentration antagonized the hyperalgesia induced by naloxone on day seven (P = 0.33). In a second experiment in rats with inflammatory pain, exposure to low concentrations of sevoflurane (1.0 and 1.5%) did not reduce fentanyl-induced hyperalgesia (P [ 0.05), but nevertheless antagonized the naloxone induced hyperalgesia on day seven (P = 0.061). Conclusion Relatively low sevoflurane concentrations (1.0%) reverse fentanyl-induced hyperalgesia in rats without inflammatory pain. Nevertheless, the lack of effect of sevoflurane concentrations of 1.0% and 1.5% to oppose hyperalgesia following high-dose fentanyl and inflammatory pain suggests that sevoflurane anti-hyperalgesic properties are weak. RésuméObjectif Les opioı¨des sont largement utilise´s en anesthe´sie mais induisent paradoxalement une hypersensibiliteṕ ostope´ratoire a`la douleur via une modulation des re´cepteurs N-me´thyl-D-aspartate (NMDA). Les effets du

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Halothane Antagonizes Effect of Morphine on the Motor Reaction Threshold in Rats

Cited by 15 publications

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Volatile anaesthetics antagonize nitrous oxide and morphine-induced analgesia in the rat

Volatile anaesthetics antagonize nitrous oxide and morphine-induced analgesia in the rat

Antinociceptive Agents as General Anesthetic Adjuncts: Supra-additive and Infra-additive Interactions

Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats

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