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Canadian Journal of Anesthesia/Journal canadien d'anesthésie

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01.02.2009 | Reports of Original Investigations

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

verfasst von: Philippe Richebé, MD, PhD, Bertrand Rivalan, MD, Cyril Rivat, PhD, Jean-Paul Laulin, PhD, Gérard Janvier, MD, PhD, Pierre Maurette, MD, PhD, Guy Simonnet, PhD

Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Ausgabe 2/2009

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Abstract

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 × 60 μg kg⁻¹) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 × 60 μg 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.

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Titel: Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats
verfasst von: Philippe Richebé, MD, PhD
Bertrand Rivalan, MD
Cyril Rivat, PhD
Jean-Paul Laulin, PhD
Gérard Janvier, MD, PhD
Pierre Maurette, MD, PhD
Guy Simonnet, PhD
Publikationsdatum: 01.02.2009
Verlag: Springer-Verlag
Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Ausgabe 2/2009
Print ISSN: 0832-610X
Elektronische ISSN: 1496-8975
DOI: https://doi.org/10.1007/s12630-008-9023-4

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