Opioid induced hyperalgesia is a paradoxical reaction characterized by an enhanced perception of pain related to the use of these drugs in the absence of disease progression or withdrawal syndrome. In contrast to cases of tolerance, defined as the loss of analgesic potency during prolonged use of opioids, no improvement is seen with dose escalation. Opioid induced hyperalgesia could be manifested in the context of maintenance dosing and withdrawal, at very high or escalating doses, and at

more »

... low doses. To establish a differential diagnosis is important to consider that increasing the dose may produce a temporary improvement in patients with tolerance but not in those who develop hyperalgesia. Pathogenesis of this phenomenon is not well defined, but there are several experimental studies in animal models and in humans that have shown that hyperalgesia is not triggered by a single factor. Proposed mechanisms include: NMDA receptor mediation, modulation by the calcium/calmodulin protein kinase, the increase in the number of nociceptors or excitatory neurotransmitters release. There are different treatment strategies available, such as the reduction in the dose of opioid used, opioid rotation or association of other analgesic. Other options are NMDA receptor antagonists or combination therapy with COX-2 inhibitors. In this paper we review recent advances in the understanding of the underlying mechanisms, clinical studies and available treatment strategies.