Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats.
OBJECTIVE
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 x 60 microg kg(-1)) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 x 60 microg 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).


CONCLUSIONS
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.
Richebé
Philippe
P
Laboratoire Homéostasie-Allostasie-Pathologie-Rehabilitation, Université Bordeaux 2, Université Bordeaux 1, CNRS UMR 5227, 146 rue Léo Saignat, 33076, Bordeaux Cedex, France. philippe.richebe@u-bordeaux2.fr
Rivalan
Bertrand
B
Rivat
Cyril
C
Laulin
Jean-Paul
JP
Janvier
Gérard
G
Maurette
Pierre
P
Simonnet
Guy
G
D000701:Analgesics, Opioid / Q000633:toxicity*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000633:toxicity*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D000077149:Sevoflurane
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; D000077149:Sevoflurane; D002351:Carrageenan; D005283:Fentanyl