Articles: opioid.
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Several studies suggest that heteromerization between μ (MOP) and δ (DOP) opioid receptors modulates the signalling properties of the individual receptors. For example, whereas activation of MOP receptors by an agonist induces G protein-mediated signalling, the same agonist induces β-arrestin-mediated signalling in the context of the MOP-DOP receptor heteromer. Moreover, heteromer-mediated signalling is allosterically modulated by a combination of MOP and DOP receptor ligands. This has implications in analgesia given that morphine-induced antinociception can be potentiated by DOP receptor ligands. Recently reagents selectively targeting the MOP-DOP receptor heteromer such as bivalent ligands, antibodies or membrane permeable peptides have been generated; these reagents are enabling studies to elucidate the contribution of endogenously expressed heteromers to analgesia as well as to the development of side-effects associated with chronic opioid use. Recent advances in drug screening technology have led to the identification of a MOP-DOP receptor heteromer-biased agonist that activates both G protein-mediated and β-arrestin-mediated signalling. Moreover, this heteromer-biased agonist exhibits potent antinociceptive activity but with reduced side-effects, suggesting that ligands targeting the MOP-DOP receptor heteromer form a basis for the development of novel therapeutics for the treatment of pain. In this review, we summarize findings regarding the biological and functional characteristics of the MOP-DOP receptor heteromer and the in vitro and in vivo properties of heteromer-selective ligands. ⋯ This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
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The sufentanil sublingual tablet system (SSTS) is a novel patient-controlled analgesia (PCA) system that is pending approval from the US FDA for the management of moderate to severe acute pain in hospitalized patients. SSTS offers a noninvasive alternative to intravenous (iv.) PCA and optimized on-demand analgesia with the rapid onset and titratibility of sublingual sufentanil. Phase III clinical trials have demonstrated that SSTS has greater efficacy for the treatment of pain during the 72-h postoperative period after open abdominal and major orthopedic (total knee or total hip arthroplasty) surgery compared with iv. ⋯ Safety assessments indicate that adverse events are typical for postoperative patients taking opioid analgesics. While the frequency of adverse events is comparable between patients using SSTS and iv. PCA MS, the incidence of oxygen desaturation is lower in those using SSTS.
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Korean J. Intern. Med. · Jan 2015
Multicenter StudyThe efficacy of low-dose transdermal fentanyl in opioid-naïve cancer patients with moderate-to-severe pain.
Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naïve patients with moderate-to-severe cancer pain. ⋯ Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.
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Drug Alcohol Depend · Jan 2015
ReviewPsychophysiology of pain and opioid use: implications for managing pain in patients with an opioid use disorder.
Opioid therapy is one component of an effective pain management regimen for patients with chronic pain and the majority of these patients use their medications responsibly. However, there are a growing number of these patients who develop an opioid use disorder and in some cases require opioid replacement therapy. Managing these patients is complex and the underlying mechanisms of pain and addiction are not well understood. Developing an effective interdisciplinary treatment program for the individual with pain and an opioid use disorder will depend on enhancing our knowledge of the psychophysiology of pain and addiction. ⋯ Individuals with a history of opioid misuse have greater levels of hyperalgesia which may be due to alterations in psychophysiological pathways. More research is needed into the psychophysiological biomarkers among individuals with comorbid pain and addiction in order to develop better treatment approaches and improve outcomes among this difficult to treat population.
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Cancer pain is one of the most important symptoms of malignant disease, which has a major impact on the quality of life of cancer patients. Therefore, it needs to be treated appropriately after a careful assessment of the types and causes of pain. ⋯ There is a major need for more and better randomized controlled trials in the setting of cancer pain as the lack of evidence is hampering the improvement of current treatment guidelines.