Pronociceptive effects of remifentanil in a mouse model of postsurgical pain: effect of a second surgery.
BACKGROUND
Remifentanil anesthesia enhances postoperative pain in animals and humans. The authors evaluated the impact of the dose (microg x kg(-1) x min(-1)) and duration of remifentanil infusion, and the effects of a second surgery on postoperative pain sensitization.


METHODS
Mice received different doses of remifentanil over 30 or 60 min. The authors assessed thermal (Hargreaves) and mechanical hyperalgesia (von Frey) at 2, 4, 7, and 10 days. In other experiments, mice had a plantar incision during sevoflurane with or without remifentanil anesthesia that was repeated 27 days later, when nociceptive thresholds returned to baseline. Linear mixed models were used for statistical analysis.


RESULTS
Remifentanil induced dose-dependent pronociceptive effects with calculated ED(50)s of 1.7 (95% confidence interval, 1.3-2.1) and 1.26 (1.0-1.6) microg x kg(-1) x min(-1) for thermal and mechanical hyperalgesia, respectively, which lasted longer with higher doses (P < 0.001). The duration of infusion did not alter the pronociceptive effects of remifentanil when administered at a constant dose of infusion. When given during surgery, high (2.66 microg x kg(-1) x min(-1)) or low (0.66 microg x kg(-1) x min(-1)) remifentanil increased the extent (P < 0.05) and duration (P < 0.01) of thermal and mechanical hyperalgesia. The latter was further enhanced after a second surgery performed in the same experimental conditions (P < 0.05). Surgery or remifentanil infusion, each one individually, induced significant mechanical hyperalgesia, which was greater when repeated (P < 0.05).


CONCLUSIONS
In this model of incisional pain, remifentanil induces pronociceptive effects, which are dose dependent but unaltered by the duration of administration. A second surgery performed on the same site and experimental conditions induces greater postoperative hyperalgesia that is enhanced when remifentanil is used as an anesthetic.
Cabañero
David
D
Anesthesiology Research Unit, Institut Municipal de Investigacions Mèdiques, Department of Anesthesiology, Hospital del Mar, Universitat Autònoma de Barcelona.
Campillo
Ana
A
Célérier
Evelyne
E
Romero
Asunción
A
Puig
Margarita M
MM
D000701:Analgesics, Opioid / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000523:psychology; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000139:chemically induced* / Q000523:psychology; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology*; D000077208:Remifentanil
D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D010880:Piperidines; D000077208:Remifentanil