Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine

The aim of this study was to assess the preventative effect of ketamine on the exaggerated postoperative pain observed in sufentanil-treated mice and its ability to improve the analgesic effectiveness of morphine during the postoperative period in an orthopaedic model of pain. In this study, we assessed the effects of ketamine on sufentanil enhancement of pain behaviour induced by fracture and the effects of ketamine on postoperative morphine-induced analgesia. Three tests were used to assess pain behaviour: von Frey filament application, hot-plate test, and a subjective pain scale. When administered 1 day after surgery in mice treated with sufentanil on D0 (before surgery), morphine induced an analgesic effect as observed by the nociceptive threshold increase in saline- and ketamine-treated mice. Morphine was more effective in ketamine-treated (1 and 50 mg kg(-1)) mice. Our results suggest that pre-emptive use of ketamine is useful in orthopaedic surgery in this mice model to diminish short- and long-term hyperalgesia, but also to improve morphine effectiveness leading to a better mobilization and more rapid rehabilitation.