Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human
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TLDR
A wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals are described and evaluated as they are used to study opioid efficacy, tolerance, addiction and dependence.Abstract:
Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence.
LINKED ARTICLES
This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4read more
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Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.
John T. Williams,Susan L. Ingram,Graeme Henderson,Charles Chavkin,Mark von Zastrow,Stefan Schulz,Thomas Koch,Christopher J. Evans,MacDonald J. Christie +8 more
TL;DR: There are large gaps in understanding the molecular processes responsible for loss of MOR function after chronic exposure to opioids, and further elucidation of the cellular mechanisms that are regulated by opioids will be necessary for the successful development of MOR-based approaches to new pain therapeutics that limit the development of tolerance.
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Dynorphin Acts as a Neuromodulator to Inhibit Itch in the Dorsal Horn of the Spinal Cord
Adam P. Kardon,Erika Polgár,Junichi Hachisuka,Lindsey M. Snyder,D. F. Cameron,Sinead Savage,Xiaoyun Cai,Sergei Karnup,Christopher R. Fan,Gregory M. Hemenway,Carcha S. Bernard,Erica S. Schwartz,Hiroshi Nagase,Christoph Schwarzer,Masahiko Watanabe,Takahiro Furuta,Takeshi Kaneko,H. Richard Koerber,Andrew J. Todd,Sarah E. Ross +19 more
TL;DR: It is shown that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by Menthol, suggesting that kappa opioids may be a broadly effective therapy for pathological itch.
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Cebranopadol: A Novel Potent Analgesic Nociceptin/Orphanin FQ Peptide and Opioid Receptor Agonist
Klaus Linz,Thomas Christoph,Thomas M. Tzschentke,Thomas Koch,Klaus Schiene,Michael Gautrois,Wolfgang P. Schröder,Babette Kögel,Horst Beier,Werner Englberger,Stefan Schunk,Jean De Vry,Ulrich Jahnel,Stefanie Frosch +13 more
TL;DR: Cebranopadol, by its combination of agonism at NOP and opioid receptors, affords highly potent and efficacious analgesia in various pain models with a favorable side effect profile.
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Mechanisms of rapid opioid receptor desensitization, resensitization and tolerance in brain neurons.
Vu C Dang,MacDonald J. Christie +1 more
TL;DR: This review will examine notions based on dogma that β‐arrestin‐2 (βarr‐2) binding causes MOR desensitization and/or that MOR endocytosis and recycling are required for receptor resensItization in light of recent evidence establishing that MOR dephosphorylation and resensitizing do not require endocyTosis.
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Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment
TL;DR: The receptor, preclinical and clinical pharmacology of fentanyl is reviewed, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use is reviewed.
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