Articles: opioid.
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Fentanyl is a synthetic opioid that is widely used in anesthesiology, but its illicit use is rapidly increasing. At high doses, fentanyl induces unconsciousness and muscle rigidity, the mechanisms of which are poorly understood. Since animal models are needed to study these effects, the aim of this study was to establish a rat model of fentanyl abuse and investigate the effects of repeated high-dose fentanyl injections on loss of righting reflex, heart rate, respiratory depression, muscle, and brain activity. ⋯ The authors established a rodent model of repeated high-dose fentanyl administration. Overall, significant evidence of tolerance was not observed after 10 exposures of high-dose fentanyl for any of the analyzed parameters. These results suggest that tolerance does not develop for fentanyl-induced unconsciousness, muscle rigidity, or respiratory depression.
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Prescription opioids for noncancer pain in the United Kingdom have increased over the past 2 decades, alongside associated harms. Policies addressing opioid prescribing must be tailored to individual patient needs with specific disease systems. The aim of this study was to evaluate clinical conditions associated with new opioid initiation in noncancer pain using nationally representative UK data. ⋯ This is the first study in the United Kingdom evaluating large-scale national data to assess indications associated with opioid initiation. Nearly 3 quarters of new opioid prescriptions for noncancer pain were in patients with musculoskeletal conditions, often for conditions with limited evidence for opioid efficacy. These findings could inform targeted interventions and future policies to support nonpharmacological interventions in the most common conditions where opioid harms outweigh benefits.
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The development of nonopioid analgesics for the treatment of abdominal pain is a pressing clinical problem. To address this, we examined the expression of G i/o -coupled receptors, which typically inhibit nociceptor activation, in colonic sensory neurons. This led to the identification of the orphan receptor GPR35 as a visceral analgesic drug target because of its marked coexpression with transient receptor potential ankyrin 1 (TRPA1), a mediator of noxious mechanotransduction in the bowel. ⋯ Consistent with this mechanism of action, we confirmed that TRPA1-mediated colonic contractions evoked by SP release were abolished by CS pretreatment in a GPR35-dependent manner. Our data demonstrate that GPR35 agonists prevent the activation and sensitisation of colonic nociceptors through the inhibition of TRPA1-mediated SP release. These findings highlight the potential of GPR35 agonists to deliver nonopioid analgesia for the treatment of abdominal pain.
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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
Ultrasound-Guided Percutaneous Cryoneurolysis for the Treatment of Pain following Traumatic Rib Fracture: A Randomized, Active-Controlled, Participant- and Observer-Masked Study.
Traumatic rib fractures are associated with pain lasting weeks to months and a decreased ability to inspire deeply or cough to clear secretions. Ultrasound-guided percutaneous cryoneurolysis involves reversibly ablating peripheral nerve(s) using exceptionally low temperature with a transdermal probe, resulting in a prolonged nerve block with a duration measured in months. The authors hypothesized that cryoneurolysis would improve analgesia and inspired volume after rib fracture. ⋯ Ultrasound-guided percutaneous cryoneurolysis improves maximum inspired lung volume while concurrently decreasing pain and opioid consumption after traumatic rib fracture. These results should be considered preliminary, requiring confirmation with a trial including a larger sample size.