Opioid-induced hyperalgesia and tolerance: understanding opioid side effects

Opioid-induced pain or opioid tolerance should be considered when opioid therapy fails to provide expected analgesic effects or when there is unexplainable pain exacerbation following opioid treatment. As a result, an increase in the opioid dosage may not be the solution to ineffective opioid therapy for chronic pain management. A decrease in the opioid mass may actually provide pain relief in many instances. At one time, it was anticipated that opioid-induced pain was related to upregulation of NMDA receptors with a downregulation of mu receptors. However, there is growing evidence to suggest the opioid receptor-based hyperalgesic mechanism may be directly modulated by the NMDA receptor. Furthermore, the mechanism that causes opioid tolerance may be the same mechanism that causes opioid-induced pain. Current evidence suggests that opioid-induced pain sensitivity could be prevented by interrupting the cellular and molecular changes associated with the development of opioid tolerance. Continued research may lead the way to a new period in which patients prone to opioid-induced pain could be identified, allowing one to tailor pharmacologic pain therapy to each patient.