Articles: opioid.
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Randomized Controlled Trial
Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial.
Central sensitization is modulated by the endogenous opioid system and plays a major role in the development and maintenance of pain. Recent animal studies performed following resolution of inflammatory pain showed reinstatement of tactile hypersensitivity induced by administration of a mu-opioid-antagonist, suggesting latent sensitization is mediated by endogenous opioids. In a recent crossover study in healthy volunteers, following resolution of a first-degree burn, 4 out of 12 volunteers developed large secondary areas of hyperalgesia areas after a naloxone infusion, while no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans. ⋯ We aim to demonstrate opioid-mediated latent sensitization in a post-surgical setting, using pain as a clinical relevant variable. Impairment of the protective endogenous opioid system may play an important role in the transition from acute to chronic pain. In order to sufficiently block the endogenous opioid system, a high-dose target-controlled naloxone-infusion is used, in accordance with recent findings in animal studies.
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J Subst Abuse Treat · Nov 2015
The characteristics of a cohort who tamper with prescribed and diverted opioid medications.
To describe the methods and baseline characteristics of a cohort of people who tamper with pharmaceutical opioids, formed to examine changes in opioid use following introduction of Reformulated OxyContin®. ⋯ Findings highlight the heterogeneity in the patterns and clinical correlates of opioid use among people who tamper with pharmaceutical opioids. Targeted health interventions are essential to reduce the associated harms.
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Randomized Controlled Trial Comparative Study
Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended-Release Oxycodone Formulations with Abuse-Deterrent Properties.
Oxycodone DETERx® is an extended-release (ER), microsphere-in-capsule abuse-deterrent-formulation designed to retain its extended-release properties following tampering or misuse (e.g., chewing, crushing). This study assessed the safety and pharmacokinetics of orally administered intact and crushed Oxycodone DETERx® capsules compared with intact and crushed reformulated OxyContin® tablets and crushed immediate-release oxycodone tablets (IR oxycodone). ⋯ These data demonstrate that when crushed and taken orally, Oxycodone DETERx® maintains its EXTENDED-release profile, while crushed OxyContin® shows a pharmacokinetic profile similar to an immediate-release product. These results suggest that Oxycodone DETERx® may be less attractive to illicit drug users compared with existing abuse-deterrent-formulations, while providing a safer option for patients who may unknowingly crush their medication such as those who have difficulty swallowing.
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Interactions between exogenous and endogenous opioids are not commonly investigated as a basis for sexually dimorphic opioid analgesia. We investigated the influence of spinal endomorphin 2 (EM2), an endogenous mu-opioid receptor (MOR) ligand, on the spinal antinociception produced by intrathecally administered opioids. Activation of spinal MORs facilitated spinal EM2 release. This effect was sexually dimorphic, occurring in males but not in females. Although activational effects of testosterone were required for opioid facilitation of spinal EM2 release in males, the absence of this facilitation in females did not result from either insufficient levels of testosterone or mitigating effects of estrogens. Strikingly, in males, the contribution of spinal EM2 to the analgesia produced by intrathecally applied MOR agonists depended on their analgesic efficacy relative to that of EM2. Spinal EM2 released by the higher efficacy MOR agonist sufentanil diminished sufentanil's analgesic effect, whereas EM2 released by the lower efficacy morphine had the opposite effect on spinal morphine antinociception. Understanding antithetical contributions of endogenous EM2 to intrathecal opioid antinociception not only enlightens the selection of opioid medications for pain management but also helps to explain variable sex dependence of the antinociception produced by different opioids, facilitating the acceptance of sexually dimorphic antinociception as a basic tenet. ⋯ The male-specific MOR-coupled enhancement of spinal EM2 release implies a parallel ability to harness endogenous EM2 antinociception. The inferred diminished ability of females to utilize the spinal EM2 antinociceptive system could contribute to their greater frequency and severity of chronic pain syndromes.
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British journal of pain · Nov 2015
Prescribing opioid analgesics for chronic non-malignant pain in general practice - a survey of attitudes and practice.
This study replicates a previous postal survey of general practitioners (GPs) to explore whether attitudes to opioid prescribing have changed at a time when the number of opioid prescriptions issued in primary care has increased. ⋯ Given the national trend for increased opioid prescriptions, it is unsurprising that more frequent self-reported prescribing is reported here; however, increased frequency does not translate into less reluctance about prescribing. The effectiveness of strong opioids for chronic pain is recognised, but concerns about addiction, dependence and misuse inform a reluctance to use strong opioids. These juxtapositions highlight a continued need for clearer understanding of GPs' perceptions of strong opioids and point to the potential benefit of dedicated guidelines or specialist education and training to address their uncertainties.