McQuay H: Opioids in pain management

Pain Research, Nuffield Department of Anaesthetics, University of Oxford, The Churchill, Oxford Radcliffe Hospital, Headington, UK.
The Lancet (Impact Factor: 45.22). 07/1999; 353(9171):2229-32. DOI: 10.1016/S0140-6736(99)03528-X
Source: PubMed


Opioids are our most powerful analgesics, but politics, prejudice, and our continuing ignorance still impede optimum prescribing. Just over 100 years ago, opium poppies were still grown on the Cambridgeshire fens in the UK to provide oblivion for the working man and his family, but the brewing lobby argued on thin evidence that their potions were less dangerous. The restriction of opioid availability to protect society and the individual continues in many countries. In this review I focus on chronic and cancer pain, but many of the principles apply in acute pain. The justification for this focus is that patients with chronic pain may suffer longer and unnecessarily if we prescribe and legislate badly.

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    • "Another advantage of melatonin analogues over other classes of analgesics is their lack of abuse potential and withdrawal symptoms upon discontinuation of the treatment ( Lemoine et al . , 2011 ) and their safer profile compared to opioids ( McQuay , 1999 ) . "
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    ABSTRACT: Melatonin is a neurohormone involved in the regulation of both acute and chronic pain whose mechanism is still not completely understood. We have recently demonstrated that selective MT2 melatonin receptor partial agonists have antiallodynic properties in animal models of chronic neuropathic pain by modulating ON/OFF cells of the descending antinociceptive system. Here, we examined the antinociceptive properties of the selective MT2 melatonin receptor partial agonists N-{2-[(3-methoxyphenyl)phenylamino]ethyl}acetamide (UCM765) and N-{2-[(3-bromophenyl)-(4-fluorophenyl)amino]ethyl}acetamide (UCM924) in two animal models of acute and inflammatory pain: the hot-plate and formalin tests. UCM765 and UCM924 (5-40mg/kg, s.c.) dose-dependently increased the temperature of the first hind paw lick in the hot-plate test, and decreased the total time spent licking the injected hind paw in the formalin test. Antinociceptive effects of UCM765 and UCM924 were maximal at the dose of 20mg/kg. At this dose, the effects of UCM765 and UCM924 were similar to those produced by 200mg/kg acetaminophen in the hot-plate test, and by 3mg/kg ketorolac or 150mg/kg MLT in the formalin test. Notably, antinociceptive effects of the two MT2 partial agonists were blocked by the pre-treatment with the MT2 antagonist 4-phenyl-2-propionamidotetralin (4P-PDOT, 10mg/kg) in both paradigms. These results demonstrate the antinociceptive properties of UCM765 and UCM924 in acute and inflammatory pain models and corroborate the concept that MT2 melatonin receptor may be a novel target for analgesic drug development. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · European journal of pharmacology
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    • "Although their use is often limited by several unwanted effects, opioids remain the gold standard of care for the treatment of moderate to severe pain (McQuay, 1999). Clinically available opioids produce their effects mainly through the μ opioid receptor (MOP receptor). "
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    ABSTRACT: Phosphorylation of delta opioid receptors (DOPrs) by Cyclin-dependent kinase 5 (Cdk5) was shown to regulate the trafficking of this receptor. Therefore, we aimed to determine the role of Cdk5 in regulating DOPrs in rats treated with morphine or with the complete Freund's adjuvant (CFA). Since mu (MOPrs) and DOPrs are known to be co-regulated, we also sought to determine if Cdk5-mediated regulation of DOPr also affects MOPr functions. The role of Cdk5 in regulating opioid receptors in CFA- and morphine-treated rats was studied using roscovitine as a Cyclin-dependent kinase inhibitor and a cell-penetrant peptide mimicking the second intracellular loop of DOPr (C11-DOPri2). Opioid receptor functions were assessed in vivo in a series of behavioral experiments and correlated by measuring ERK1/2 activity in dorsal root ganglia homogenates. Chronic roscovitine treatment reduced the antinociceptive and antihyperalgesic effects of deltorphin II (Dlt II) in morphine- and CFA-treated rats, respectively. Repeated administrations of C11-DOPri2 also robustly decreased Dlt II-induced analgesia. Interestingly, DAMGO-induced analgesia was significantly increased by roscovitine and C11-DOPri2. Concomitantly, in roscovitine-treated rats the Dlt II-induced ERK1/2 activation was decreased, whereas the DAMGO-induced ERK1/2 activation was increased. An acute roscovitine treatment has no effect on Dlt II- or DAMGO-induced analgesia. Together, our results demonstrate that Cdk5 is a key player in the regulation of DOPr in morphine- and CFA-treated rats and that the regulation of DOPr by Cdk5 is sufficient to modulate MOPr functions through an indirect process. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jan 2015 · British Journal of Pharmacology
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    • "Morphine is widely used for the alleviation of severe acute and chronic pain and is considered to be among the most effective analgesics (Ballantyne and Mao 2003; McQuay 1999). It is also widely known that its long-term use and abuse are associated with detrimental effects, such as tolerance, physical dependence, and addiction (Ballantyne and LaForge 2007; Hojsted and Sjogren 2007). "
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    ABSTRACT: Rationale Recent animal studies reported that curcumin, the active constituent of Curcuma longa, has several central actions and may attenuate morphine tolerance. Objectives In the present study, we utilized the intracranial self-stimulation (ICSS) paradigm to examine the effects of the commercially available curcuminoid mixture and each one of its components, individually, on brain stimulation reward and on the reward-facilitating effect of morphine. Methods Male Sprague-Dawley rats were implanted with an electrode into the medial forebrain bundle and trained to respond for electrical stimulation using a rate-frequency paradigm. In the first study, rats were injected with graded doses either of the curcuminoid mixture, or curcumin I, or II, or III. In the second study, we examined whether a low dose of the curcuminoid mixture or each individual curcumin analogue composing it could counteract the reward-facilitating effect of morphine. Results At low doses, both the curcuminoid mixture and curcumin I did not affect brain stimulation reward, whereas, higher doses increased ICSS thresholds. Curcumin II and curcumin III did not affect brain stimulation reward at any doses. Subthreshold doses of the curcuminoid mixture and curcumin I inhibited the reward-facilitating effect of morphine. Conclusion Both the curcuminoid mixture and curcumin I lack hedonic properties and moderate the reward-facilitating effect of morphine. Our data suggest that curcumin interferes with brain reward mechanisms responsible for the expression of the acute reinforcing properties of opioids and provide evidence that curcumin may be a promising adjuvant for attenuating morphine's rewarding effects in patients who are under long-term opioid therapy.
    Full-text · Article · May 2014 · Psychopharmacology
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