Articles: opioid.
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μ-Opioid receptor agonists are widely used within the contemporary treatment of pain, but abrupt opioid suspension, even after short-term infusion, can paradoxically increase the sensitivity to noxious stimuli, a phenomenon that has been, for example, reported after application of the fast-acting μ-opioid receptor agonist remifentanil. To investigate the mechanisms underlying the effects of discontinuation of remifentanil application on pain processing in the human CNS, we analyzed neuronal responses to thermal stimuli before and after a short-term infusion of remifentanil (30 min 0.1 μg/kg body weight/min) compared with control in the brain, brainstem, and spinal cord in drug-naive male volunteers using fMRI. Subsequent to remifentanil suspension, we observed reduced heat pain thresholds and increased neuronal responses in pain-encoding as well as in key regions of the descending pain-modulatory system, such as the periaqueductal gray matter, the nucleus cuneiformis, and the rostral ventromedial medulla. ⋯ SIGNIFICANCE STATEMENT Opioids are widely used in modern medicine, but, in addition to their known side effects, it is increasingly recognized that opioids can also increase sensitivity to pain subsequent to their use. Using the fast-acting μ-opioid receptor agonist remifentanil and fMRI in healthy male volunteers, this study demonstrates how signaling changes occur along the entire descending pain-modulatory pathway after opioid discontinuation and how these alterations are closely linked to increased behavioral pain sensitivity. Particularly by revealing modified responses in pain-modulatory brainstem regions that have been previously demonstrated to be causally involved in acute opioid withdrawal effects in rodents, the data provide a plausible neuronal mechanism by which the increased sensitivity to pain after opioid suspension is mediated in humans.
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Practice Guideline
Management of opioid use disorders: a national clinical practice guideline.
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J Pain Symptom Manage · Mar 2018
ReviewInvestigation of the practices, legislation, supply chain and regulation of opioids for clinical pain management in Southern Africa: A multi-sectoral, cross-national, mixed methods study.
Sub-Saharan Africa faces an increasing incidence and prevalence of life-limiting and life-threatening conditions. These conditions are associated with a significant burden of pain linked to high morbidity and disability that is poorly assessed and undertreated. Barriers to effective pain management partly relate to lack of access to opioid analgesia and challenges in their administration. ⋯ Policies and relevant laws should be updated to ensure that the legislative environment supports opioid access for pain management. Action plans for improving pain treatment for patients suffering from HIV or non-communicable diseases should address barriers at the different levels of the supply chain that involve policymakers, administrators, and service providers.