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Opioid-induced hyperalgesia (OIH) is a state of sensitization of pain receptors caused by opioid use. In OIH, there is a paradoxical response to opioids, in which opioids that are used to produce analgesia will instead induce sensitization to certain painful stimuli. The resulting pain might be similar or different from the original pain for which the opioids were taken. OIH is a characteristic phenomenon that could explain the loss of opioid effectiveness in many patients. The exact molecular mechanism for OIH is not yet fully understood. However, four proposed mechanisms are being considered in the present review to explain OIH including; N-methyl-D-aspartate (NMDA) receptor activation; spinal dynorphin; descending facilitation; and finally decreased reuptake and enhanced nociceptive response. It is important for clinicians to consider OIH in opioid-treated patients, particularly for any new appearance of unexplained pain, or when increasing the opiate dose results in worsening of the pain. OIH is managed by reducing opioid dosage, tapering opiods off, and adding NMDA receptor antagonists.
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