Article

Mechanisms of Opioid-Induced Tolerance and Hyperalgesia

Department of Pharmaceutics, University of Washington Seattle, Seattle, Washington, United States
Pain Management Nursing (Impact Factor: 1.53). 10/2007; 8(3):113-21. DOI: 10.1016/j.pmn.2007.02.004
Source: PubMed

ABSTRACT

Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.

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Available from: Danny D Shen, Feb 10, 2015
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    • "However in morphine tolerance, the mechanism is still unclear. Nowadays, study suggests opioid receptor desensitization and down regulation as two theories that can explain the phenomenon (DuPen et al., 2007). The desensitization of opioid receptor in brain may occur due to prolonged exposure to opioids, by alteration of GPCR (Yoburn et al., 2003). "

    Full-text · Article · Nov 2015 · Journal of Applied Pharmaceutical Science
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    • "However in morphine tolerance, the mechanism is still unclear. Nowadays, study suggests opioid receptor desensitization and down regulation as two theories that can explain the phenomenon (DuPen et al., 2007). The desensitization of opioid receptor in brain may occur due to prolonged exposure to opioids, by alteration of GPCR (Yoburn et al., 2003). "

    Full-text · Article · Jan 2015 · Journal of Applied Pharmaceutical Science
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    • "Opioids have been used to alleviate moderate to severe pain. Although opioids are potent analgesics, treatment of opioids can also cause a state of nociceptive sensitization, often referred to as opioid-induced hyperalgesia and allodynia [10] [11]. There is strong evidence to implicate the importance of N-methyl- D-aspartate (NMDA) receptors to the induction and maintenance of central and peripheral sensitization in these pain hypersensitivities [12]. "
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    ABSTRACT: Background In this study, we investigated the effects of locally (intraplantar) applied remifentanil, a μ opioid receptor agonist, to the paws and tested whether locally N-methyl d-aspartate (NMDA) receptors agonist or antagonist can modify remifentanil-induced effects in diabetic rats. Methods Effects of locally (intraplantar) remifentanil, NMDA and MK801 or their combinations were investigated by measuring the latencies, thresholds and two biochemical parameters (malondialdehyde (MDA) and nitric oxide (NO)), in streptozotocin induced diabetic rats. Results Diabetic rats exhibited hyperalgesia and allodynia and remifentanil treatment aggravated the hyperalgesia and allodynia. The hyperalgesic and allodynic effects of remifentanil decreased in diabetic rats as compared to healthy rats. MK801 suppressed the hyperalgesic and allodynic actions of remifentanil in diabetic rats. However, hyperalgesic and allodynic actions of NMDA increased in diabetic rats. In contrast to age matched group, the combination of NMDA and remifentanil did not produce synergistic actions in diabetic rats. The levels of MDA and NO in the paw tissues of the diabetic rats significantly increased. MK801 significantly decreased NO levels, but not MDA, in diabetic rats. Conclusions The hyperalgesic and allodynic actions of locally treated remifentanil may decrease in diabetic conditions. Increases in NMDA receptors activation, reactive oxygen species production and NO release may modify the sensitivity to remifentanil in diabetes induced neuropathic pain states.
    Full-text · Article · Dec 2014 · Pharmacological reports: PR
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