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- Hansen, Johan Liseth, et al.
(author)
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Problematic opioid use among osteoarthritis patients with chronic post-operative pain after joint replacement: analyses from the BISCUITS study
- 2023
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In: Scandinavian Journal of Pain. - : WALTER DE GRUYTER GMBH. - 1877-8860 .- 1877-8879. ; 23:2, s. 353-363
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Journal article (peer-reviewed)abstract
- Objectives: Opioids are commonly used to manage pain, despite an increased risk of adverse events and complications when used against recommendations. This register study uses data of osteoarthritis (OA) patients with joint replacement surgery to identify and characterize problematic opioid use (POU) prescription patterns.Methods: The study population included adult patients diagnosed with OA in specialty care undergoing joint replacement surgery in Denmark, Finland, Norway, and Sweden during 1 January 2011 to 31 December 2014. Those with cancer or OA within three years before the first eligible OA diagnosis were excluded. Patients were allocated into six POU cohorts based on dose escalation, frequency, and dosing of prescription opioids post-surgery (definitions were based on guidelines, previous literature, and clinical experience), and matched on age and sex to patients with opioid use, but not in any of the six cohorts. Data on demographics, non-OA pain diagnoses, cardiovascular diseases, psychiatric disorders, and clinical characteristics were used to study patient characteristics and predictors of POU.Results: 13.7% of patients with OA and a hip/knee joint replacement were classified as problematic users and they had more comorbidities and higher pre-surgery doses of opioids than matches. Patients dispensing high doses of opioids pre-surgery dispensed increased doses post-surgery, a pattern not seen among patients prescribed lower doses pre-surgery. Being dispensed 1-4,500 oral morphine equivalents in the year pre-surgery or having a non-OA pain diagnosis was associated with post-surgery POU (OR: 1.44-1.50, and 1.11-1.20, respectively).Conclusions: Based on the discovered POU predictors, the study suggests that prescribers should carefully assess pain management strategies for patients with a history of comorbidities and pre-operative, long-term opioid use. Healthcare units should adopt risk assessment tools and ensure that these patients are followed up closely. The data also demonstrate potential areas for further exploration in improving patient outcomes and trajectories.
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| 2. |
- Hygge Blakeman, Karin
(author)
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The role of galanin in chronic pain mechanisms
- 2002
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Doctoral thesis (other academic/artistic)abstract
- The general aim of these studies is to further elucidate the role of galanin in pain mechanisms. We have utilized normal and genetically modified animals and a variety of techniques. In order to use genetically modified mice to study chronic pain, we adapted a photochemically-induced, peripheral nerve ischemia model, originally developed in rats, to mice. Both morphological and behavioral studies were conducted to determine the optimal irradiation time for producing hypersensitivity after partial nerve injury. This model was then used to study galanin over-expressing mice and mice lacking the galanin receptor 1. The normal basal response of these mice to sensory testing was also determined. During basal conditions, the over-expressing mice showed less sensitivity to thermal stimulation than the normal controls. After the photochemically-induced peripheral nerve ischemia, the over- expressing mice showed reduced development of heat and mechanical hyperalgesia as compared to wild-type mice. In contrast, the mice lacking the galanin receptor 1 displayed hypersensitivity to cold and heat in the hot-plate test under basal condition. After photochemically-induced nerve injury these mice exhibited a longer lasting hypersensitivity than wild-type controls, and this was not due to a slower nerve regeneration. A microdialysis technique to measure the release of galanin in the dorsal horn of the spinal cord in rat was developed. Using this method it could be demonstrated that electrical stimulation of primary afferent C-fibers causes release of galanin in the dorsal horn. of normal rats. The data presented in this thesis suggest that galanin primarily plays an inhibitory role in nociception under basal conditions. This role is further strengthened after peripheral nerve ischemia, where endogenous galanin appears to reduce the severity and duration of pain-like behaviors via activation of galanin receptor 1.
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| 3. |
- Macsari, Istvan, et al.
(author)
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3-Oxoisoindoline-1-carboxamides : Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na(V)1.7 with Efficacy in Rat Pain Models
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:15, s. 6866-6880
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Journal article (peer-reviewed)abstract
- The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure activity relationships, and in vitro and in vivo characterization of a novel series of Na(V)1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na(V)1.7 potency, selectivity over Na(V)1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity versus Na(V)1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclinical behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.
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