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Updated: Jun 6, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Opioid-induced hyperalgesia (OIH)
Plínio da Cunha Leal1, Jefferson Clivatti, João Batista Santos Garcia
1Department of Anesthesiology, Pain, and Intensive Care Medicine of the Escola Paulista de Medicina of Universidade Federal de São Paulo (EPM/UNIFESP), SP.
Background And Objectives:
Opioids 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.
Contents:
The 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.
Conclusions:
This is a very complex subject, which involves a series of pathophysiological mechanisms that could contribute for OIH and patient discomfort, bringing disastrous consequences.
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