Opioid-induced hyperalgesia: fact or fiction?

© 2008 SAGE Publications, Los Angeles, London, New Delhi and Singapore 10.1177/0269216307086857 Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Accumulating evidence suggests that opioids may cause opioid-induced hyperalgesia. Somewhat paradoxically, opioid therapy aiming at alleviating pain may render patients more sensitive to pain and potentially may aggravate their pre-existing pain. Several recent articles have reviewed and highlighted important aspects of opioid-induced hyperalgesia, which reflects the growing interest and rapidly expanding body of literature regarding this phenomenon.1–5 The term ‘paradoxical pain’ has been used in the past and associated with the now unfounded theory of morphine-3-glucuronide being antalgesic.6 The term ‘hyperalgesia’ is more informative from both a mechanistic and clinical viewpoint. An increase in pain to noxious stimuli must have been witnessed at some point by every palliative care professional, albeit this clinical phenomenon will have been interpreted in different ways. An increase in pain to noxious stimuli, or hyperalgesia, can occur in two types of syndrome. The first is part of the triad of opioid toxicity and also includes to variable degrees, hallucinations, vivid dreams, myoclonic jerks, confusion, agitation and drowsiness. The second form of hyperalgesia occurs as an isolated phenomenon in patients who are taking opioid medication and in whom there are none of the classical signs of opioid toxicity. In both situations clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that the administration of opioids can activate both pain inhibitory and pain facilitatory systems. The exact mechanism of hyperalgesia with opioid toxicity and without opioid toxicity is unclear and may be very different in each of these two broad conditions. There will be a third group of patients in whom the diagnosis of opioid-induced hyperalgesia is missed and escalation of the dose of opioid results in opioid toxicity.