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 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

The Effects of Anesthetics on Chronic Pain After Breast Cancer Surgery

“…26,27 Although sevoflurane prevents sensitization by inhibiting the N-methyl-d-aspartate receptor, this effect cannot sufficiently prevent chronic pain. 28 Anesthetics did not show significant effects on the severity of chronic pain. We are unsure of the interpretation of this finding.…”

Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis

“…However, propofol has been shown to be able to prevent remifentanil-induced hyperalgesia in volunteers 65 and patients after surgery, 18 whereas sevoflurane has only weak anti-hyperalgesic effects in fentanyl-induced hyperalgesia in rat. 66 In conclusion, the prevention by propofol of the development of remifentanilinduced hyperalgesia and related consequences in patients after surgery deserve further clinical evaluation.…”

Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review

“…However, Solt et al (2006) documented that sevoflurane has only a minimal inhibitory effect on NMDA receptors, which are considered to be involved in the development of opioid-related hypersensitivity (Tompkins and Campbell, 2011). Relatively low sevoflurane concentrations (1.0%) reverse OIH, but there was the lack of effect of sevoflurane concentrations of 1.0 and 1.5% to oppose hyperalgesia following high-dose opioids (Solt et al, 2006; Richebe et al, 2009). Shin et al (2010) also suggested that remifentanil-induced hyperalgesia was not apparent during propofol anesthesia compared with the effect produced during sevoflurane anesthesia even though dosage of remifentanil was increased from 1.0 to 4.0 ng/ml.…”