Multi-mechanistic analgesia for opioid-induced hyperalgesia

J Clin Pharm Ther. 2012 Apr;37(2):125-7. doi: 10.1111/j.1365-2710.2011.01264.x. Epub 2011 Apr 19.


What is known and objective: The phenomenon of opioid-induced hyperalgesia (OIH), an increased sensitivity to pain attributed to the very opioid drugs administered to manage the pain, is well established in animal models, and there is concern that it also occurs in patients. Our objective is to briefly summarize the basic science and clinical evidence about OIH as background to consider the possible benefit of using a multi-mechanistic analgesic approach.

Comment: It is unclear how OIH occurs, or even why; presumably, it is part of an adaptive response. But development of OIH poses a serious treatment dilemma. OIH differs from tolerance, which also presents as reduced analgesic effect, in that tolerance is addressed by judicious and monitored increase in opioid dose, but OIH would be treated by a decrease in opioid dose. Therefore, it is important to avoid induction of OIH. Currently, it is not clear which patients are at greater risk of developing OIH, or which drugs are at greater risk of producing it.

What is new and conclusion: We suggest that multi-mechanistic analgesia, accomplished within either a single drug or a combination of drugs, is a logical approach that might result in a reduced development of OIH.

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Animals
  • Humans
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / prevention & control
  • Pain / drug therapy*
  • Risk Factors


  • Analgesics, Opioid