Opioids are the most potent drugs for treatment of acute and chronic pain. However, accumulating evidence suggests that opioids may paradoxically also enhance pain, often referred to as opioid-induced hyperalgesia. Opioid-induced hyperalgesia is defined as an increased sensitivity to pain or a decreased pain threshold in response to opioid therapy. Several mechanisms have been proposed to support opioid-induced hyperalgesia. However, it remains unclear whether opioid-induced hyperalgesia develops during continuous chronic application of opioids or on their withdrawal. This review provides a comprehensive summary of clinical research concerning opioid-induced hyperalgesia and the molecular mechanisms of opioid withdrawal and opioid tolerance and other potential mechanisms which might induce hyperalgesia during opioid therapy will be discussed. The status quo of our knowledge will be summarized and the clinical relevance of opioid-induced hyperalgesia will be discussed.
