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The Opiate Receptors pp 439–455Cite as

Molecular Modulation of In Vivo Tolerance

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Part of the book series: The Receptors ((REC))

Abstract

Opioid tolerance can limit the clinical utility of opioids for pain management. It is a neuroadaptive response to the repeated administration of an opioid. Opioid tolerance is predominantly of the pharmacological (nonassociative) and pharmacodynamic type. Possible contributions to tolerance at the receptor level include receptor desensitization, internalization, and recycling. Alterations of G proteins, other intracellular signaling cascades and receptor–receptor interactions also may be involved. At the systems level, opioid-induced hyperalgesia, N-methyl-d-aspartate receptor mechanisms, activation of the immune system, and genetic factors have all been implicated. Each of these potential contributors is discussed. Establishing the mechanism(s) of tolerance remains an elusive as well as a continuing challenge. However, some of the mechanisms discussed in this chapter appear to have the potential to provide new approaches for reducing or eliminating the development of opioid tolerance.

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Acknowledgements

CEI is supported in part by NIDA grant DA001457 and NIDA center grant DA005130. AMG was supported by NIDA training grant DA007274.

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Authors and Affiliations

  1. Department of Pharmacology, Weill Medical College of Cornell University, New York, NY, 10065, USA

    Charles E. Inturrisi

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  1. Charles E. Inturrisi
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  2. Ann M. Gregus
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Correspondence to Charles E. Inturrisi .

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  1. , Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Gavril W. Pasternak

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Inturrisi, C.E., Gregus, A.M. (2011). Molecular Modulation of In Vivo Tolerance. In: Pasternak, G. (eds) The Opiate Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-993-2_16

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