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Anesthesiology Oct 2023Chronic pain is a public health concern that affects approximately 1.5 billion people globally. Conventional therapeutic agents including opioid and non-opioid... (Review)
Review
Chronic pain is a public health concern that affects approximately 1.5 billion people globally. Conventional therapeutic agents including opioid and non-opioid analgesics have been associated with adverse side effects, issues with addiction, and ineffective analgesia. Novel agents repurposed to treat pain via different mechanisms are needed to fill the therapeutic gap in chronic pain management. Psychedelics such as lysergic acid diethylamide and psilocybin (the active ingredient in psychedelic mushrooms) are thought to alter pain perception through direct serotonin receptor agonism, anti-inflammatory effects, and synaptic remodeling. This scoping review was conducted to identify human studies in which psychedelic agents were used for the treatment of pain. Twenty-one articles that assessed the effects of psychedelics in treating various pain states were included. The present scarcity of clinical trials and small sample sizes limit their application for clinical use. Overall, psychedelics appear to show promise for analgesia in patients with certain headache disorders and cancer pain diagnoses. Future studies must aim to examine the combined effects of psychotherapy and psychedelics on chronic pain.
Topics: Humans; Hallucinogens; Chronic Pain; Pain Management; Pain Perception; Analgesia; Drug-Related Side Effects and Adverse Reactions
PubMed: 37698433
DOI: 10.1097/ALN.0000000000004673 -
Neuron Sep 2023Ongoing pain is driven by the activation and modulation of pain-sensing neurons, affecting physiology, motor function, and motivation to engage in certain behaviors. The...
Ongoing pain is driven by the activation and modulation of pain-sensing neurons, affecting physiology, motor function, and motivation to engage in certain behaviors. The complexity of the pain state has evaded a comprehensive definition, especially in non-verbal animals. Here, in mice, we used site-specific electrophysiology to define key time points corresponding to peripheral sensitivity in acute paw inflammation and chronic knee pain models. Using supervised and unsupervised machine learning tools, we uncovered sensory-evoked coping postures unique to each model. Through 3D pose analytics, we identified movement sequences that robustly represent different pain states and found that commonly used analgesics do not return an animal's behavior to a pre-injury state. Instead, these analgesics induce a novel set of spontaneous behaviors that are maintained even after resolution of evoked pain behaviors. Together, these findings reveal previously unidentified neuroethological signatures of pain and analgesia at heightened pain states and during recovery.
Topics: Mice; Animals; Pain; Analgesia; Analgesics; Pain Management; Neurons; Nociception
PubMed: 37442132
DOI: 10.1016/j.neuron.2023.06.008 -
Peptides Nov 2023This paper is the forty-fifth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles... (Review)
Review
This paper is the forty-fifth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2022 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).
Topics: Animals; Humans; Female; Pregnancy; Opioid Peptides; Analgesics, Opioid; Analgesia; Analgesics, Non-Narcotic; Drug Tolerance
PubMed: 37704079
DOI: 10.1016/j.peptides.2023.171095 -
Anasthesiologie, Intensivmedizin,... Oct 2023Patient safety and reduction of possible complications are the top priorities for anesthesiologists in everyday clinical practice. Thus, interdisciplinary early...
Patient safety and reduction of possible complications are the top priorities for anesthesiologists in everyday clinical practice. Thus, interdisciplinary early assessment and optimization of patient specific medical conditions and risk factors are crucial. In obstetrics, regional anesthesia and general anesthesia are routinely being performed. To ensure maternal and fetal safety, knowledge regarding physiological changes during pregnancy is highly important. Regional anesthesia, particularly epidural analgesia, has its main field of application in the context of natural birth in the delivery room. Spinal anesthesia, as well as epidural and combined spinal-epidural anesthesia (CSE) are widely used for caesarean section. In this context, special attention should be paid to possible bleeding disorders. The combination of risk stratification and strategies to improve the patient's preoperative medical status is capable to reduce maternal and fetal complications.
Topics: Pregnancy; Humans; Female; Anesthesia, Obstetrical; Cesarean Section; Analgesia, Epidural; Anesthesia, Spinal; Anesthesia, Epidural; Analgesia, Obstetrical
PubMed: 37832560
DOI: 10.1055/a-2043-4329 -
British Journal of Anaesthesia Nov 2023Open major abdominal surgery is one of the most risky surgical procedures for acute postoperative pain. Thoracic epidural analgesia (TEA) has been considered the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Open major abdominal surgery is one of the most risky surgical procedures for acute postoperative pain. Thoracic epidural analgesia (TEA) has been considered the standard analgesic approach. In different reports, lidocaine i.v. has been shown to have an analgesic efficacy comparable with TEA. We compared the analgesic efficacy of i.v. lidocaine with thoracic epidural analgesia using bupivacaine in patients undergoing major abdominal surgery.
METHODS
In this noninferiority clinical trial, 210 patients were randomised to thoracic epidural bupivacaine with morphine or i.v. lidocaine. Dynamic pain at 24 h after surgery was measured using a numerical pain rating scale (NPR), and morphine consumption was also measured. A difference in i.v. the lidocaine-epidural bupivacaine NPR of ≤1 for dynamic pain was considered a noninferiority margin.
RESULTS
The NPR for dynamic pain in the lidocaine group at 24 h was between 5.7 (1.8) and 5.2 (1.9) in the epidural group, with a difference of 0.53 (95% confidence interval 0.0-1.0). In the first 24 h, the average difference in morphine consumption was 1.8 mg between the i.v. lidocaine and epidural groups (95% confidence interval 1-3 mg). No differences were found in adverse events or complications associated with the procedures.
CONCLUSIONS
Intravenous lidocaine is noninferior to thoracic epidural analgesia for acute postoperative pain control in major abdomial surgery at 24 h postoperatively.
CLINICAL TRIALS REGISTRATION
NCT04017013.
Topics: Humans; Analgesia, Epidural; Analgesia, Patient-Controlled; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Lidocaine; Morphine; Pain, Postoperative
PubMed: 37758623
DOI: 10.1016/j.bja.2023.07.032 -
JAMA Network Open Aug 2023Dural-puncture epidural (DPE) and standard epidural are common modes of neuraxial labor analgesia. Little is known about conversion of DPE-initiated labor analgesia to... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Dural-Puncture Epidural vs Standard Epidural for Epidural Extension on Onset Time of Surgical Anesthesia in Elective Cesarean Delivery: A Randomized Clinical Trial.
IMPORTANCE
Dural-puncture epidural (DPE) and standard epidural are common modes of neuraxial labor analgesia. Little is known about conversion of DPE-initiated labor analgesia to surgical anesthesia for cesarean delivery.
OBJECTIVE
To determine whether DPE provides a faster onset and better-quality block compared with the standard epidural technique for cesarean delivery.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind, randomized clinical trial was conducted between April 2019 and October 2022 at a tertiary care university hospital (University of Arkansas for Medical Sciences). Participants included women aged 18 years and older undergoing scheduled cesarean delivery with a singleton pregnancy.
INTERVENTIONS
Participants were randomized to receive DPE or standard epidural in the labor and delivery room. A T10 sensory block was achieved and maintained using a low concentration of bupivacaine with fentanyl through the epidural catheter until the time of surgery. Epidural extension anesthesia was initiated in the operating room.
MAIN OUTCOMES AND MEASURES
The primary outcome was the time taken from chloroprocaine administration to surgical anesthesia (T6 sensory block). The secondary outcome was the quality of epidural anesthesia, as defined by a composite of the following factors: (1) failure to achieve a T10 bilateral block preoperatively in the delivery room, (2) failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, (3) requirement for intraoperative analgesia, (4) repeat neuraxial procedure, and (5) conversion to general anesthesia.
RESULTS
Among 140 women (mean [SD] age, 30.1 [5.2] years), 70 were randomized to the DPE group, and 70 were randomized to the standard epidural group. The DPE group had a faster onset time to surgical anesthesia compared with the standard epidural group (median [IQR], 422 [290-546] seconds vs 655 [437-926] seconds; median [IQR] difference, 233 [104-369] seconds). The composite rates of lower quality anesthesia were 15.7% (11 of 70 women) in the DPE group and 36.3% (24 of 66 women) in the standard epidural group (odds ratio, 0.33; 95% CI, 0.14-0.74; P = .007).
CONCLUSIONS AND RELEVANCE
Anesthesia initiated following a DPE technique resulted in faster onset and improved block quality during epidural extension compared with initiation with a standard epidural technique. Further studies are needed to confirm these findings in the setting of intrapartum cesarean delivery.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03915574.
Topics: Pregnancy; Female; Humans; Adult; Analgesia, Obstetrical; Labor, Obstetric; Anesthesia, Epidural; Punctures
PubMed: 37526934
DOI: 10.1001/jamanetworkopen.2023.26710 -
Current Protocols Apr 2024Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. This practice is necessary for performing invasive...
Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. This practice is necessary for performing invasive procedures, achieving prolonged immobility for sensitive imaging modalities (magnetic resonance imaging, for instance), and providing intra- and post-procedural pain relief. In addition to facilitating the procedures performed by the investigator, the provision of anesthesia and analgesia is crucial for the preservation of animal welfare and for humane treatment of animals used in research. Furthermore, anesthesia and analgesia are important components of animal use protocols reviewed by Institutional Animal Care and Use Committees, requiring careful consideration and planning for the particular animal model. In this article, we provide technical guidance for the investigator, covering the provision of anesthesia by two routes (injectable and inhalant), guidelines for monitoring anesthesia, current techniques for recognition of pain, considerations for administering preventative analgesia, and considerations for post-operative care. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Injectable anesthesia Basic Protocol 2: Inhalant anesthesia Basic Protocol 3: Assessing pain.
Topics: Animals; Mice; Analgesia; Anesthesia; Pain Management; Pain Measurement
PubMed: 38646951
DOI: 10.1002/cpz1.1006 -
Current Pain and Headache Reports Sep 2023Postoperative pain continues to be one of the most common challenges following surgeries. Multimodal analgesia has been of particular focus as non-opioid alternatives... (Review)
Review
PURPOSE OF REVIEW
Postoperative pain continues to be one of the most common challenges following surgeries. Multimodal analgesia has been of particular focus as non-opioid alternatives have been encouraged due to concerns of the opioid epidemic. Ketamine has been an especially useful adjunct in multimodal pain regimens within the past few decades. This article highlights the current use and advances surrounding the perioperative use of ketamine.
RECENT FINDINGS
Ketamine has antidepressive effects at subanesthetic doses. Intraoperative ketamine may be beneficial in reducing postoperative depression. Additionally, newer studies are exploring whether ketamine can be useful in reducing postoperative sleep disturbances. Ketamine continues to be a great tool in perioperative pain control, especially during an opioid epidemic. As its use continues to expand and gain more popularity in the perioperative period, more research could shed light on the additional nonanalgesic benefits of ketamine use.
Topics: Humans; Ketamine; Analgesics, Opioid; Pain Management; Analgesia; Pain, Postoperative
PubMed: 37392333
DOI: 10.1007/s11916-023-01128-z -
The British Journal of Surgery Jan 2024Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients...
BACKGROUND
Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.
METHODS
This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.
RESULTS
The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (β coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.
CONCLUSION
Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely.
Topics: Humans; Analgesics, Opioid; Patient Satisfaction; Patient Discharge; Prospective Studies; Pain Measurement; Pain, Postoperative; Practice Patterns, Physicians'; Analgesia
PubMed: 38207169
DOI: 10.1093/bjs/znad421 -
Anesthesiology Dec 2023Labor neuraxial analgesia may reduce the odds of postpartum hemorrhage, the leading indication for maternal blood transfusion during childbirth. This study tested the...
BACKGROUND
Labor neuraxial analgesia may reduce the odds of postpartum hemorrhage, the leading indication for maternal blood transfusion during childbirth. This study tested the hypothesis that labor neuraxial analgesia is associated with reduced odds of maternal blood transfusion overall.
METHODS
U.S. birth certificate data in the Natality File of the National Vital Statistics System for all 50 states from 2015 to 2018 for vaginal and intrapartum cesarean deliveries were analyzed. The exposure was labor neuraxial analgesia. The primary outcome was maternal blood transfusion, recorded on the birth certificate, which has low sensitivity for this outcome. Adjusted odds ratios and 95% CIs of blood transfusion associated with neuraxial analgesia were estimated using propensity score matching. The adjusted odds ratios were estimated overall and according to delivery mode, and treatment effect was compared between vaginal and intrapartum cesarean deliveries using an interaction term. Sensitivity analyses were performed using inverse propensity score weighting and quantitative bias analysis for outcome misclassification.
RESULTS
Of the 12,503,042 deliveries analyzed, 9,479,291 (75.82%) were with neuraxial analgesia, and 42,485 (0.34%) involved maternal blood transfusion. After propensity score matching, the incidence of blood transfusion was 0.30% in women without neuraxial analgesia (7,907 of 2,589,493) and 0.20% in women with neuraxial analgesia (5,225 of 2,589,493), yielding an adjusted odds ratio of 0.87 (95% CI, 0.82 to 0.91) overall. For intrapartum cesarean deliveries, the adjusted odds ratio was 0.55 (95% CI, 0.48 to 0.64), and for vaginal deliveries it was 0.93 (95% CI,. 0.88 to 0.98; P value for the interaction term < 0.001). The results were consistent in the sensitivity analyses, although the quantitative bias analysis demonstrated wide variation in potential effect size point estimates.
CONCLUSIONS
Labor neuraxial analgesia may be associated with reduced odds of maternal blood transfusion in intrapartum cesarean deliveries and, to a lesser extent, vaginal deliveries. The specific effect size varies widely by delivery mode and is unclear given the poor sensitivity of the data set for the maternal transfusion primary outcome.
Topics: Pregnancy; Female; Humans; Labor, Obstetric; Delivery, Obstetric; Cesarean Section; Pain Management; Analgesia, Epidural; Retrospective Studies
PubMed: 37585507
DOI: 10.1097/ALN.0000000000004743