Fig 1 Effect of ketamine on the sufentanil enhancement of mechanical hyperalgesia (protocol A). No difference in the measured parameter was observed in.

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Fig 1 Effect of ketamine on the sufentanil enhancement of mechanical hyperalgesia (protocol A). No difference in the measured parameter was observed in any of the group after fracture and before treatment (a). At D0, sufentanil produced antinociceptive effects shortly after its administration (b). Sufentanil resulted in opioid-induced hyperalgesia from D0 to D3 (a). Sufentanil–ketamine association has produced antinociceptive effects shortly after its administration (b). Ketamine associated with sufentanil prevented opioid-induced hyperalgesia when compared with the sufentanil group; ketamine alone had no antinociceptive effect. The symbols represent median and inter-quartile range. *P<0.05, the ketamine 50/sufentanil group vs the sufentanil group; <sup>§</sup>P<0.05, the sufentanil group vs the control group; <sup>+</sup>P<0.05, the ketamine 1/sufentanil group vs the sufentanil group. From: Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine† Br J Anaesth. 2009;104(2):231-238. doi:10.1093/bja/aep363 Br J Anaesth | © The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Fig 2 Effect of ketamine on the sufentanil enhancement of thermal hyperalgesia in (protocol A). No difference in the measured parameter was observed in any of the group after fracture and before treatment (a). At D0, sufentanil produced antinociceptive effects shortly after its administration (b). Then sufentanil has resulted in opioid-induced hyperalgesia from D0 to D4 (a). Sufentanil–ketamine association has produced antinociceptive effects shortly after its administration (b). Ketamine associated with sufentanil has prevented opioid-induced hyperalgesia when compared with the sufentanil group; ketamine alone had no antinociceptive effect. The symbols represent median and inter-quartile range. *P<0.05, the ketamine 50/sufentanil group vs the sufentanil group; <sup>§</sup>P<0.05, the sufentanil group vs the control group; <sup>+</sup>P<0.05, the ketamine 1/sufentanil group vs the sufentanil group. From: Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine† Br J Anaesth. 2009;104(2):231-238. doi:10.1093/bja/aep363 Br J Anaesth | © The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Fig 3 Effect of ketamine on the sufentanil enhancement of a subjective pain scale (protocol A). No difference in the measured parameter was observed in any of the group after fracture and before treatment (a). At D0, sufentanil produced antinociceptive effects shortly after its administration (b). No changes in the subjective pain scale were seen after D0 (a). Sufentanil–ketamine association has antinociceptive effects shortly after its administration (b). The symbols represent median and inter-quartile range. *P<0.05, the ketamine 50/sufentanil group vs the sufentanil group; <sup>§</sup>P<0.05, the sufentanil group vs the control group; <sup>+</sup>P<0.05, the ketamine 1/sufentanil group vs the sufentanil group. From: Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine† Br J Anaesth. 2009;104(2):231-238. doi:10.1093/bja/aep363 Br J Anaesth | © The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Fig 4 Effect of ketamine on the analgesic effect of a single morphine injection on mechanical hyperalgesia (protocol B). No difference in the measured parameter was observed in any of the group after fracture and before treatment. When administered 1 day after surgery in mice treated with sufentanil on D0, 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 mice. The symbols represent median and inter-quartile range. *P<0.05, the ketamine 50/sufentanil group vs the sufentanil group; <sup>+</sup>P<0.05, the ketamine 1/sufentanil group vs the sufentanil group. From: Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine† Br J Anaesth. 2009;104(2):231-238. doi:10.1093/bja/aep363 Br J Anaesth | © The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Fig 5 Effect of ketamine on the analgesic effect of a single morphine injection on a subjective pain (protocol B). No difference in the measured parameter was observed in any of the group after fracture and before treatment. When administered 1 day after surgery in mice treated with sufentanil on D0, 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 mice. The symbols represent median and inter-quartile range. *P<0.05, the ketamine 50/sufentanil group vs the sufentanil group; <sup>+</sup>P<0.05, the ketamine 1/sufentanil group vs the sufentanil group. From: Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine† Br J Anaesth. 2009;104(2):231-238. doi:10.1093/bja/aep363 Br J Anaesth | © The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Fig 6 Effect of ketamine on the analgesic effect of a single morphine injection on thermal hyperalgesia (protocol B). No difference in the measured parameter was observed in any of the group after fracture and before treatment. No difference was found between the groups concerning thermal nociception after morphine administration probably because of the maximal threshold fixed at 12 s. The symbols represent median and inter-quartile range. *P<0.05, the ketamine 50/sufentanil group vs the sufentanil group; <sup>+</sup>P<0.05, the ketamine 1/sufentanil group vs the sufentanil group. From: Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine† Br J Anaesth. 2009;104(2):231-238. doi:10.1093/bja/aep363 Br J Anaesth | © The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org