Articles: analgesics.
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The management of peri-operative pain is one of the pillars of anaesthesia and is of particular importance in patients undergoing surgery for solid malignant tumours. Amongst several options, the most commonly employed analgesic regimens involve opioids, NSAIDs and regional anaesthesia techniques with different local anaesthetics. In recent years, several research reports have tried to establish a connection between peri-operative anaesthesia care and outcome after cancer surgery. ⋯ The reason for this might lie with the nature of tumour biology itself, and in the diversity of patient and tumour phenotypes. In a translational approach, future research should therefore concentrate on patient and tumour-related factors or biomarkers, which might either influence the tumour and its microenvironment or predict potential responses to interventions, including the choice of the analgesic. This might not only be relevant for the daily practice of clinical anaesthesia, but would also be of great importance for patients undergoing cancer surgery, who might be able to receive an individualised anaesthetic regimen based on their phenotypic profile.
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Randomized Controlled Trial
METHA-NeP: effectiveness and safety of methadone for neuropathic pain: a controlled randomized trial.
In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. ⋯ No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.
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Voltage-gated sodium (Na v ) channels present untapped therapeutic value for better and safer pain medications. The Na v 1.8 channel isoform is of particular interest because of its location on peripheral pain fibers and demonstrated role in rodent preclinical pain and neurophysiological assays. To-date, no inhibitors of this channel have been approved as drugs for treating painful conditions in human, possibly because of challenges in developing a sufficiently selective drug-like molecule with necessary potency not only in human but also across preclinical species critical to the preclinical development path of drug discovery. ⋯ In this report, we have leveraged numerous physiological end points in nonhuman primates to evaluate the analgesic and pharmacodynamic activity of a novel, potent, and selective Na v 1.8 inhibitor compound, MSD199. These pharmacodynamic biomarkers provide important confirmation of the in vivo impact of Na v 1.8 inhibition on peripheral pain fibers in primates and have high translational potential to the clinical setting. These findings may thus greatly improve success of translational drug discovery efforts toward better and safer pain medications, as well as the understanding of primate biology of Na v 1.8 inhibition broadly.
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Meta Analysis
Cannabinoids for Acute Postoperative Pain Management: A Systematic Review and Meta-Analysis of Clinical Trials.
Poor acute postoperative pain control, coupled with the use of intravenous medications with a limited and unsafety efficacy spectrum, has led to new therapeutic alternative explorations to reduce adverse events while increasing its analgesic efficacy. There cannabinoids have been proposed as a useful control agent in post-surgical pain. Nevertheless, to date, there is no solid evidence to evaluate them. The current article sought to determine cannabinoids' effectiveness and safety in the aforementioned context. ⋯ The management of severe pain after surgery, and the use of intravenous drugs with limited and potentially unsafe effectiveness, has led to the exploration of new treatment options to minimize side effects while improving pain relief. Cannabinoids have been suggested as a potential solution for managing post-surgical pain, but there is currently insufficient evidence to assess their effectiveness. The purpose of this article was to evaluate the effectiveness and safety of cannabinoids in this context.