Opioid-induced hyperalgesia: pain hurts?

In the current issue of the British Journal of Anaesthesia, Shin and colleagues report that propofol used for the maintenance of general anaesthesia may prevent remifentanilinduced hyperalgesia. In their study, a comparison of propofol and sevoflurane combined with either high dose or low dose of remifentanil for the maintenance of general anaesthesia in breast cancer surgery was conducted. They showed that remifentanil hyperalgesia was induced only by a high dose of remifentanil during sevoflurane anaesthesia but not in propofol anaesthesia. Furthermore, propofol and high-dose remifentanil-based anaesthesia provided better postoperative analgesia compared with sevoflurane and high-dose remifentanil. This is an interesting finding which provides further evidence that the use of high doses of remifentanil intraoperatively may elevate postoperative pain scores, and subsequently increase the opioid requirements and the occurrence of their adverse effects in patients. From a clinical perspective, this study indicates that the use of high-dose remifentanil for lengthy procedures may best be avoided, as patients’ postoperative comfort could be compromised. Although total postoperative opioid use was meticulously monitored, it remains unclear what the number and the duration of intense pain periods (VAS.7) were. Intense pain sets off a cascade of neuronal events, but relationship of these with the development of chronic pain remains unclear. The study also raises the question whether the increased pain scores and increased demand for opioids observed after operation could be associated with remifentanil-induced hyperalgesia, with remifentanilinduced tolerance, or with both. The International Association of the Study of Pain (IASP) defines hyperalgesia as ‘an increased response to a stimulus which is normally painful’. Therefore, the increased perception of pain after remifentanil-based anaesthesia could be associated with opioid-induced hyperalgesia. In contrast, it is well established that chronic opioid therapy is associated with the development of tolerance which refers to ‘a decrease in susceptibility to the effects of opioid due to its continued administration’. The potential of opioids to induce acute tolerance after short-term administration during anaesthesia in surgery has not been fully established. Apparently, hyperalgesia and tolerance after short-term exposure of remifentanil for anaesthesia might even co-exist. Some insight into this was in a study of postoperative pain scores in patients after major abdominal surgery who had received high-dose remifentanil (mean dose 0.3 mg kg min) perioperatively. In this study, patients with high-dose remifentanil anaesthesia required morphine earlier and needed greater doses to achieve satisfactory analgesia, after operation. Another observation in this study was that this increased morphine demand extended for several hours after operation. The authors explained their findings in the context of the development of acute opioid tolerance due to greater morphine requirement for the high-dose remifentanil group. Furthermore, the observation of the increased and prolonged morphine demand after operation was associated with the development of hyperalgesia. The study supported the possibility of the co-existence of tolerance and hyperalgesia in high-dose remifentanil anaesthesia. Clinical pain models using healthy volunteers have been utilized to investigate the effect of the short-term administration of opioids and provide direct evidence for the existence of opioid-induced hyperalgesia. – 7 In 2007, Schmidt Volume 105, Number 5, November 2010