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Neuropharmacology Jun 2019Opioid drugs are important tools to alleviate pain of different origins, but they have strong addictive potential and their abuse at higher doses often results in... (Review)
Review
Opioid drugs are important tools to alleviate pain of different origins, but they have strong addictive potential and their abuse at higher doses often results in serious health complications. Respiratory depression that leads to brain hypoxia is perhaps the most dangerous symptom of acute intoxication with opioids, and it could result in lethality. The development of substrate-specific sensors coupled with amperometry made it possible to directly evaluate physiological and drug-induced fluctuations in brain oxygen levels in awake, freely-moving rats. The goal of this review paper is to consider changes in brain oxygen levels induced by several opioid drugs (heroin, fentanyl, oxycodone, morphine). While some of these drugs are widely used in clinical practice, they all are abused, often at doses exceeding the clinical range and often resulting in serious health complications. First, we consider some basic knowledge regarding brain oxygen, its physiological fluctuations, and mechanisms involved in regulating its entry into brain tissue. Then, we present and discuss data on brain oxygen changes induced by each opioid drug within a wide range of doses, from low, behaviorally relevant, to high, likely to be self-administered by drug users. These data allowed us to compare the effects of these drugs on brain oxygen in terms of their potency, time-course, and their potential danger when used at high doses via rapid-onset administration routes. While most data discussed in this work were obtained in rats, we believe that these data have clear human relevance in addressing the alarming rise in lethality associated with the opioid abuse.
Topics: Analgesics, Opioid; Animals; Brain; Fentanyl; Heroin; Humans; Hypoxia, Brain; Morphine; Oxycodone; Rats; Respiratory Insufficiency
PubMed: 30735692
DOI: 10.1016/j.neuropharm.2019.02.008 -
Nature Communications Oct 2022The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms...
The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAc) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAc) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAc neurons impairs reward seeking behavior, while silencing of NAc or NAc→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.
Topics: Mice; Animals; Nucleus Accumbens; Reward; Ventral Tegmental Area; Dopaminergic Neurons; Opiate Alkaloids
PubMed: 36271048
DOI: 10.1038/s41467-022-33843-3 -
World Journal of Surgery Apr 2022The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal analgesic strategy for patients with acute pancreatitis (AP) remains unknown.
OBJECTIVE
The present systematic review and meta-analysis aims to compare the efficacy of different analgesic modalities trialled in AP.
METHODS
A systematic search of PubMed, MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science conducted up until June 2021, identified all randomised control trials (RCTs) comparing analgesic modalities in AP. A pooled analysis was undertaken of the improvement in pain scores as reported on visual analogue scale (VAS) on day 0, day 1 and day 2.
RESULTS
Twelve RCTs were identified including 542 patients. Seven trial drugs were compared: opiates, non-steroidal anti-inflammatories (NSAIDs), metamizole, local anaesthetic, epidural, paracetamol, and placebo. Across all modalities, the pooled VAS scores showed global improvement from baseline to day 2. Epidural analgesia appears to provide the greatest improvement in VAS within the first 24 h but is equivalent to opiates by 48 h. Within 24 h, NSAIDs offered similar pain-relief to opiates, while placebo also showed equivalence to other modalities but then plateaued. Local anaesthetics demonstrated least overall efficacy. VAS scores for opiate and non-opiate analgesics were comparable at baseline and day 1. The identified RCTs demonstrated significant statistical and methodological heterogeneity in pain-relief reporting.
CONCLUSIONS
There is remarkable paucity of level 1 evidence to guide pain management in AP with small datasets per study. Epidural administration appears effective within the first 24 h of AP although infrequently used and featured in only a single RCT. NSAIDs are an effective opiate sparing alternative during the first 24 h.
Topics: Analgesia; Analgesics; Analgesics, Opioid; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Humans; Opiate Alkaloids; Pain; Pain Management; Pancreatitis; Randomized Controlled Trials as Topic
PubMed: 34994837
DOI: 10.1007/s00268-021-06420-w -
Revue Medicale Suisse Oct 2023
Topics: Humans; Opiate Alkaloids; Neck Pain
PubMed: 37850812
DOI: 10.53738/REVMED.2023.19.846.1959 -
Revue Medicale Suisse Aug 2023
Topics: Humans; Opiate Alkaloids; Low Back Pain; Neck Pain; Acute Pain
PubMed: 37610198
DOI: 10.53738/REVMED.2023.19.838.1530 -
Revue Medicale Suisse Jan 2024
Topics: Humans; Opiate Alkaloids; Pain Management
PubMed: 38268354
DOI: 10.53738/REVMED.2024.20.858.130 -
Science (New York, N.Y.) Mar 2017
Topics: Centers for Disease Control and Prevention, U.S.; China; Crime; Drug Overdose; Federal Government; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Ohio; Opiate Alkaloids; Opioid-Related Disorders; United States
PubMed: 28360278
DOI: 10.1126/science.355.6332.1364 -
Spine Sep 2019
Topics: Analgesics, Opioid; Humans; Lower Extremity; Medicine; Opiate Alkaloids; Pain
PubMed: 31479040
DOI: 10.1097/BRS.0000000000003143 -
American Journal of Respiratory and... Aug 2020
Topics: Critical Care; Humans; Intensive Care Units; Opiate Alkaloids; Patient Discharge; Respiration, Artificial
PubMed: 32464072
DOI: 10.1164/rccm.202005-1815ED -
British Journal of Hospital Medicine... Sep 2022The forearm is the most common site of fracture in children. At the time of initial assessment, a thorough examination and neurovascular assessment of the limb is... (Review)
Review
The forearm is the most common site of fracture in children. At the time of initial assessment, a thorough examination and neurovascular assessment of the limb is necessary. X-rays allow evaluation of the fracture location and type, in addition to the degree of displacement. With the help of intranasal opiates, manipulation of fracture fragments can be performed in the emergency department. Immobilisation in plaster is the gold standard treatment for paediatric forearm fractures where the degree of displacement is within acceptable parameters. Manipulation and casting should be followed by orthogonal radiographs and a repeated neurovascular assessment of the limb. Oral analgesia and safety netting information should be provided on discharge and the child should be reviewed in fracture clinic within a week of the injury. This article reviews the British Orthopaedic Association Standards for Trauma and Orthopaedics for the early management of paediatric forearm fractures that do not require operative management.
Topics: Child; Forearm; Forearm Injuries; Humans; Opiate Alkaloids; Radiography; Radius Fractures
PubMed: 36193916
DOI: 10.12968/hmed.2021.0564