978-0-387-75269-3_30.pdf

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Abstract Opioid tolerance, defined by decreased analgesic efficacy of opioid analgesics after repeated and prolonged use, is a significant clinical problem limiting adequate treatment of pain with opioids, the most effective analgesics available today. After decades of research, multiple mechanisms at molecular, cellular and network levels have been proposed to account for the behavioral observation of opioid analgesic tolerance. Major mechanisms include those mediated by opioid receptor desensitization and internalization, glutamate receptors, chronic opioid-induced hyperalgesia and the cAMP-

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