BACKGROUND: In the randomized, phase 3, SUSA-301 trial, celecoxib-tramadol co-crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate-to-severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment-emergent adverse events (TEAEs).
METHODS: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of rescue medications up to 4 and 48 h post-study drug dose, stratified by baseline pain intensity (moderate/severe), and on the incidence of TEAEs, stratified by rescue medication use.
RESULTS: A significantly lower proportion of patients received any rescue medication within 4 h post-study dose with CTC (49.5%) versus tramadol (61.7%, p = 0.0178), celecoxib (65.2%, p = 0.0024), and placebo (75.3%, p = 0.0001); this was also seen for oxycodone use. Fewer patients in the CTC group received ≥3 doses of rescue medication compared with the other groups, irrespective of baseline pain intensity. In patients who did not receive opioid rescue medication, CTC was associated with a lower incidence of nausea and vomiting TEAEs versus tramadol alone. In patients who received rescue oxycodone, the incidence of nausea was similar in the CTC and tramadol groups, and higher versus celecoxib and placebo.
CONCLUSIONS: Celecoxib-tramadol co-crystal was associated with reduced rescue medication use and an acceptable tolerability profile compared with tramadol or celecoxib alone in adults with acute, moderate-to-severe, postoperative pain.

暂无摘要。

BACKGROUND: Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between cannabis use and postoperative pain levels and opioid doses within 24 hours of surgery.
METHODS: We conducted a propensity score-matched retrospective cohort study using electronic health records data of 22 476 older surgical patients with at least 24-hour hospital stays at University of Florida Health between 2018 and 2020. Of the original cohort, 2577 patients were eligible for propensity-score matching (1:3 cannabis user: non-user). Cannabis use status was determined via natural language processing of clinical notes within 60 days of surgery and structured data. The primary outcomes were average Defense and Veterans Pain Rating Scale (DVPRS) score and total oral morphine equivalents (OME) within 24 hours of surgery.
RESULTS: 504 patients were included (126 cannabis users and 378 non-users). The median (IQR) age was 69 (65-72) years; 295 (58.53%) were male, and 442 (87.70%) were non-Hispanic white. Baseline characteristics were well balanced. Cannabis users had significantly higher average DVPRS scores (median (IQR): 4.68 (2.71-5.96) vs 3.88 (2.33, 5.17); difference=0.80; 95% confidence limit (CL), 0.19 to 1.36; p=0.01) and total OME (median (IQR): 42.50 (15.00-60.00) mg vs 30.00 (7.50-60.00) mg; difference=12.5 mg; 95% CL, 3.80 mg to 21.20 mg; p=0.02) than non-users within 24 hours of surgery.
CONCLUSIONS: This study showed that cannabis use in older adults was associated with increased postoperative pain levels and opioid doses.

BACKGROUND: Virtual reality (VR) is a well-researched digital intervention that has been used for managing acute pain and anxiety in pediatric patients undergoing various medical procedures. This study focuses on investigating the role of unique patient characteristics and VR immersion level on the effectiveness of VR for managing pediatric pain and anxiety during venipuncture.
OBJECTIVE: The purpose of this study is to determine how specific patient characteristics and level of immersion during a VR intervention impact anxiety and pain levels for pediatric patients undergoing venipuncture procedures.
METHODS: This study is a secondary data analysis of 2 combined, previously published randomized control trials on 252 pediatric patients aged 10-21 years observed at Children\'s Hospital Los Angeles from April 12, 2017, to July 24, 2019. One randomized clinical trial was conducted in 3 clinical environments examining peripheral intravenous catheter placement (radiology and an infusion center) and blood draw (phlebotomy). Conditional process analysis was used to conduct moderation and mediation analyses to assess the impact of immersion level during the VR intervention.
RESULTS: Significant moderation was found between the level of immersion and anxiety sensitivity when predicting postprocedural anxiety (P=.01). Patients exhibiting the highest anxiety sensitivity within the standard of care yielded a 1.9 (95% CI 0.9-2.8; P<.001)-point elevation in postprocedural anxiety relative to individuals with high immersion levels. No other significant factors were found to mediate or moderate the effect of immersion on either postprocedural anxiety or pain.
CONCLUSIONS: VR is most effective for patients with higher anxiety sensitivity who report feeling highly immersed. Age, location of the procedure, and gender of the patient were not found to significantly impact VR\'s success in managing levels of postprocedural pain or anxiety, suggesting that immersive VR may be a beneficial intervention for a broad pediatric population.
BACKGROUND: ClinicalTrials.gov NCT04268901; https://clinicaltrials.gov/study/NCT04268901.

UNASSIGNED: Acute pain episodes, also known as vaso-occlusive crises (VOC), are a major symptom of sickle cell disease (SCD) and lead to frequent hospitalizations. The diagnosis of VOC can be challenging, particularly in adults with SCD, 50% of whom have chronic pain. Several potential biomarkers have been proposed for identifying individuals with VOC, including elevation above the baseline of various vascular growth factors, cytokines, and other markers of inflammation. However, none have been validated to date.
UNASSIGNED: We summarize prospective biomarkers for the diagnosis of acute pain in SCD, and how they may be involved in the pathophysiology of a VOC. Previous and current strategies for biomarker discovery, including the use of omics techniques, are discussed.
UNASSIGNED: Implementing a multi-omics-based approach will facilitate the discovery of objective and validated biomarkers for acute pain.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects.
METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23.
RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05).
CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

OBJECTIVE: This review aims to summarize current knowledge on the pathophysiology of pain and the role of neuro-immune crosstalk in the development of acute and chronic pain (CP). Specifically, the review focuses on the role of immune cells involved in the innate and acquired immune response, emphasizing their bidirectional interactions with the nervous systems and discussing the implications of this crosstalk on acute and CP management.
RESULTS: In the last two decades, multiple studies have uncovered the important role of the immune system in initiating, maintaining, and resolving pain stimuli. Furthermore, researchers discovered that the immune system interacts tightly with the nervous system, creating a bidirectional crosstalk in which immune cells influence the response of peripheral and central nerve fibers while neurotransmitters and neuropeptides released by nociceptors directly and indirectly modulate the immune response. The neuro-immune crosstalk in acute and CP is a complex and not fully understood process that comprise the interactions of multiple diverse molecules, bidirectional interferences, and numerous redundant processes. Despite the complexity, important steps have been taken in recent years toward explaining the specific roles of each immune cell type and molecule in the initiation, maintenance and resolution of pain. These findings may set the basis for innovative therapeutic options that target the immune system, overcoming the limitations of current treatments in providing pain relief and the disadvantages associated with opioid therapy.

UNASSIGNED: This meta-analysis aims to examine how effective ketamine is in the management of acute and preventing chronic post-thoracotomy pain by synthesizing the available research.
UNASSIGNED: A systematic literature search was conducted across PubMed, Scopus, and Cochrane Library till May 2023. Randomized Controlled Trials (RCT) examining the influence of ketamine on post-thoracotomy pain in adults were included. The intervention group included ketamine plus morphine, while the control group included morphine only. The outcome measures were opioid intake and pain scores at rest and on moving/coughing. Evidence quality was evaluated using the Cochrane Risk of Bias and GRADE assessment.
UNASSIGNED: Nine articles comprising 556 patients were selected for meta-analysis. The intervention group had a significant decrease in pain at rest (Std. Mean Difference (SMD = -0.60 with 95% CI [-0.83, -0.37]) and on movement/cough (SMD = -0.73 [-1.27, -0.18]) in the first postoperative days. Also, the ketamine group had lower opioid consumption (mg) in comparison with controls (SMD = -2.75 [-4.14, -1.36], p-value = 0.0001) in postoperative days 1-3. There was no data to assess the long-term effect of ketamine on chronic pain.
UNASSIGNED: This meta-analysis shows that ketamine use can lower acute pain levels and morphine use after thoracotomy. In the future, larger RCTs using standardized methods and assessing both short-term and long-term analgesic effects of ketamine are necessary to deepen the understanding of the issue.

OBJECTIVE: The purpose of this review is to highlight the most recent literature and guidelines regarding perioperative methadone and buprenorphine use.
RESULTS: Surgical patients taking methadone and buprenorphine are being encountered more frequently in the perioperative period, and providers are becoming more familiar with their pharmacologic properties, benefits as well as precautions. Recommendations pertaining to buprenorphine therapy in the perioperative settings have changed in recent years, owing to more clinical and basic science research. In addition to their use in chronic pain and opioid use disorders, they can also be initiated for acute postoperative pain indications, in select patients and situations. Methadone and buprenorphine are being more commonly prescribed for pain management and opioid use disorder, and their continuation during the perioperative period is generally recommended, to reduce the risk of opioid withdrawal, relapse, or inadequately controlled pain. Additionally, both may be initiated safely and effectively for acute pain management during and after the operating room period.

Free Choice Profiling (FCP) methodology allows observers to qualitatively assess animal behavior using their own vocabulary. This study aims to investigate the ability of 3 different observer groups to recognize pain-related emotions in 20 dogs using FCP methodology, and to compare FCP data with the Glasgow Composite Pain Scale-Short Form (GCPS- SF) scores. The observer groups consisted of 10 dog owners, 10 veterinary students and 10 veterinarians. Ten healthy (\"healthy\") dogs and 10 dogs showing clinical signs of pain (\"pain\") were filmed, and the resulting 20 footages were shown to observers who were blind to the pain-related nature of the study. All observers described and scored animals\' emotional expression using FCP; then, students and veterinarians scored all dogs using GCPS- SF. FCP data were analyzed using Generalized Procrustes Analysis (GPA). Spearman correlation coefficient (ρ) was used to determine the correlation among observer groups\' FCP scores of the first two FCP dimensions (DIM1 and DIM2), and to compare GCPS-SF scores with FCP scores for the students and veterinarian observer groups. Each observer group reached a significant (p < 0.001) good consensus profile. \"Healthy\" dogs were mainly described as \"quiet\" and \"lively\", while the majority of \"pain\" dogs were considered \"in pain\" and \"suffering\". The correlation among FCP scores was high between owners\' DIM1 and students\' DIM1 (ρ = -0.86), owners\' DIM2 and students\' DIM2 (ρ = 0.72) and students\' DIM2 and vets\' DIM1 (ρ = 0.70). The correlation between GCPS-SF scores and FCP scores was high for students\' DIM2 (ρ = 0.77) and for veterinarians\' DIM1 (ρ = 0.92). Qualitative methods such as FCP could be used in association with semi-quantitative methods to evaluate the effect of pain on animal emotional expression. Observers\' cultural background and personal experience did not substantially affect qualitative behavioral assessment in dogs with acute somatic pain.