• Plínio da Cunha Leal, Jefferson Clivatti, João Batista Santos Garcia, and Rioko Kimiko Sakata.
• Department of Anesthesiology, Pain, and Intensive Care Medicine of the Escola Paulista de Medicina of Universidade Federal de São Paulo (EPM/UNIFESP), SP.
• Rev Bras Anestesiol. 2010 Nov 1;60(6):639-47, 355-9.

Background And ObjectivesOpioids are commonly used for pain control; however, they can cause hyperalgesia. The reason why this can happen is not known. The objective of this review was to describe the mechanisms, factors implicated, and drug modulation.ContentsThe factors implicated in the development of opioid-induced hyperalgesia (OIH), such as duration of use, dose, and type of opioids are described. Mechanisms involved include the glutamatergic system and N-methyl-D-aspartate receptors (NMDA), spinal cyclooxygenase (COX) activation, excitatory amino acids, dynorphin, cytokines and chemokines; prostaglandins, and descending facilitation. Modulation of hyperalgesia could be done through: NMDA receptor antagonists, alpha2-adrenergic agonists, and COX inhibitors.ConclusionsThis is a very complex subject, which involves a series of pathophysiological mechanisms that could contribute for OIH and patient discomfort, bringing disastrous consequences.© 2010 Elsevier Editora Ltda. All rights reserved.

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