Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in sprague-dawley rats

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 hyperaμgesia 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 hyperaμgesia in opioid-naive rats and in rats with inflammatory pain. Methods Sevoflurane effects on hyperaμgesia 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 anaμgesic 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) hyperaμgesia classically described after high-doses of fentanyl (P>0.05). This sevoflurane concentration antagonized the hyperaμgesia 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 hyperaμgesia (P>0.05), but nevertheless antagonized the naloxone induced hyperaμgesia on day seven (P = 0.061). Conclusion Relatively low sevoflurane concentrations (1.0%) reverse fentanyl-induced hyperaμgesia in rats without inflammatory pain. Nevertheless, the lack of effect of sevoflurane concentrations of 1.0% and 1.5% to oppose hyperaμgesia following high-dose fentanyl and inflammatory pain suggests that sevoflurane anti-hyperaμgesic properties are weak. © Canadian Anesthesiologists' Society 2008.