Search

Abstract: The anterior cingulate cortex (ACC) plays a crucial role in the perception of pain. It is consistently activated by noxious stimuli and its hyperactivity in chronic pain indicates plasticity in the local neuronal network. However, the way persistent pain effects and modifies different neuronal cell types in the ACC and how this contributes to sensory sensitization is not completely understood. This study confirms the existence of 2 primary subtypes of pyramidal neurons in layer 5 of the rostral, agranular ACC, which we could classify as intratelencephalic (IT) and cortico-subcortical (SC) projecting neurons, similar to other cortical brain areas. Through retrograde labeling, whole-cell patch-clamp recording, and morphological analysis, we thoroughly characterized their different electrophysiological and morphological properties. When examining the effects of peripheral inflammatory pain on these neuronal subtypes, we observed time-dependent plastic changes in excitability. During the acute phase, both subtypes exhibited reduced excitability, which normalized to pre-inflammatory levels after day 7. Daily conditioning with nociceptive stimuli during this period induced an increase in excitability specifically in SC neurons, which was correlated with a decrease in mechanical sensitization. Subsequent inhibition of the activity of SC neurons projecting to the periaqueductal gray with in vivo chemogenetics, resulted in reinstatement of the hypersensitivity. Accordingly, it was sufficient to enhance the excitability of these neurons chemogenetically in the inflammatory pain condition to induce hypoalgesia. These findings suggest a cell type-specific effect on the descending control of nociception and a cellular mechanism for pain-induced analgesia. Furthermore, increased excitability in this neuronal population is hypoalgesic rather than hyperalgesic., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

This study aims to provide a national overview of procedural sedation and analgesia practices within Pediatric Emergency Departments in Switzerland, focusing on the availability of pharmacologic agents, the presence of safety protocols, the utilization of non-pharmacological interventions, and to identify specific local limitations. We conducted a detailed subgroup analysis of Swiss data from a European cross-sectional survey on emergency department pediatric Procedural Sedation and Analgesia (PSA) practice, isolating data from Swiss sites. The survey, conducted between November 2019 and March 2020, covered various aspects of procedural sedation and analgesia practices. The survey included nine Swiss sites, treating a total of 252,786 patients in 2019. Topical analgesia, inhaled equimolar nitrous oxide-oxygen mixture, and ketamine were largely available. All sites had nurse-directed triage protocols in place; however, opioid administration was included in the protocols in only 66% of sites. Only 33% of hospitals reported common use of intravenous sedation. Barriers to procedural sedation and analgesia implementation included staffing shortages (89% of sites) and lack of dedicated spaces (78%).Conclusions: Despite a broad array of pharmacological and options available in Swiss Pediatric Emergency Departments, challenges remain in standardizing practices across the country. Limited space and staffing and enhancing training on non-pharmacological interventions were identified as potential areas for improving pain and anxiety management in pediatric emergency care. This study underscores the need for national guidelines to harmonize emergency department PSA practices across Switzerland, ensuring all children have access to effective and evidence-based procedural comfort. What is Known: • Recent research, conducted in European emergency departments, suggests that in pediatric Procedural Sedation and Analgesia (PSA) resources are limited, and practice is heterogeneous What is New: • Swiss pediatric hospitals offer a wide range of pharmacological options for pain and anxiety management. However, significant barriers to PSA were identified. These include external control of intravenous sedation and insufficient integration of non-pharmacological interventions, such as child life specialists and procedural hypnosis. National guidelines are needed to harmonize PSA practices., (© 2024. The Author(s).)

Objective: To evaluate if students without training assess pain similarly to an expert, and to compare indications for analgesic intervention based on student opinions versus scale scoring., Study Design: Prospective, blind, randomized, cross-sectional study., Animals: Video recordings of a bull, horse, cat, pig and sheep., Methods: First-year veterinary medicine students assessed one video of a horse (n = 44) and one video of a bull (n = 39). Third-year veterinary medicine students assessed one video of a cat (n = 23) and one video of a pig (n = 21). Fourth-year animal science students (n = 16) assessed one video of a sheep. The species assessed by different student classes were determined randomly. Students were unaware of animal history or existing pain assessment and decided whether they would provide analgesia according to their opinion. They then scored each video using species-specific validated pain scales. Scores were compared with those of a board-certified anesthesiologist (expert). Chi-square test was used to compare students and expert., Results: Students underestimated the expert's score by 8-20%, except for the horse. There was no difference between the analgesic indication according to the assessment of the expert (143/143, 100%) and students (141/143, 98.6%) considering the defined analgesic intervention threshold for each scale (p = 0.478). The indication for analgesic intervention according to students' opinion (116/143, 81.1%) was lower than that according to their scale scores (141/143, 98.6%) (p < 0.0001)., Conclusions and Clinical Relevance: Students tended to underestimate pain; however, they detected pain that requires analgesic intervention in animals similarly to an expert. The use of scales optimized the indication for providing analgesia when animals were experiencing pain that required analgesic intervention., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: Shoulder dislocation, particularly anterior dislocation, is a common orthopedic injury often presenting in emergency care settings, characterized by significant pain and muscle spasms. Prompt reduction is essential to alleviate symptoms and restore function. The Cunningham technique employs gentle pulling and massage motions targeted at the muscles and has emerged as a promising method for reducing anterior shoulder dislocations. However, its reported success rates vary widely across studies, and questions remain regarding its efficacy, particularly in cases of failure. This study aims to evaluate the effectiveness of the Cunningham technique for reducing anterior shoulder dislocations and its potential role in providing analgesia and muscle relaxation as an adjunctive method., Methods: A retrospective study was conducted on patients presenting with acute anterior shoulder dislocation at a single center. Reduction using the Cunningham technique was performed initially, followed by the external rotation technique if unsuccessful. Procedural sedation and analgesia were administered if the reduction was still not achieved, and shoulder dislocation reduction was performed again through the external rotation method. The patients' VAS scores were recorded and evaluated the Cunningham technique's effectiveness in reduction and whether it increases the effectiveness of other techniques applied for reduction by lowering the VAS score, even in cases where it is not effective., Results: A total of 61 patients were included in the study. The reduction was performed using the Cunningham technique in 34.4% (21/61) patients, the external rotation technique in 47.5% (29/61) patients, and the external rotation technique with PSA in 18% (11/61) patients. Significant differences were observed in the duration of hospital stay among the three techniques, with ER with PSA resulting in the longest stay. VAS scores showed significant improvements from initial presentation to post-reduction in all three groups. A significant decrease in pre-reduction VAS scores was observed during the transition from the Cunningham technique to other techniques., Conclusion: The Cunningham technique showed effectiveness in reducing anterior shoulder dislocations, providing analgesia, and muscle relaxation. It demonstrated favorable outcomes as an initial reduction technique, with the external rotation technique used as a subsequent option. Further studies comparing the success rates and complications of the Cunningham technique with other reduction methods are warranted to establish its role in clinical practice., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Aims/Background Poorly controlled pain is common after emergency laparotomy. It causes distress, hinders rehabilitation, and predisposes to complications: prolonged hospitalisation, persistent pain, and reduced quality of life. The aim of this systematic review was to compare the relative efficacies of pre-emptive analgesia for emergency laparotomy to inform practice. Methods We performed a search of MEDLINE, MEDLINE In-Process, Embase, PubMed, Web of Science and SCOPUS for comparator studies of preoperative/intraoperative interventions to control/reduce postoperative pain in adults undergoing emergency laparotomy (EL) for general surgical pathologies. Exclusion criteria: surgery including non-abdominal sites; postoperative sedation and/or intubation; non-formal assessment of pain; non-English manuscripts. All manuscripts were screened by two investigators. Results We identified 2389 papers. Following handsearching and removal of duplicates, 1147 were screened. None were eligible for inclusion, with many looking at elective and/or laparoscopic surgeries. Conclusion Our findings indicate there is no evidence base for pre-emptive analgesic strategies in emergency laparotomy. This contrasts substantially with elective cohorts. Potential reasons include variation in practice, management of physiological derangement taking priority, and perceived contraindications to neuraxial techniques. We urge a review of contemporary practice, with analysis of clinical data, to generate expert consensus.

Objectives: There is an absence of data in the literature regarding methods to improve the patient experience during the performance of awake in-office laryngeal injections. This study sought to evaluate whether the use of local anesthetic or a vibrating instrument decreased overall pain experienced by patients with laryngeal dystonia, frequently referred to as spasmodic dysphonia (SD), undergoing transcervical botulinum toxin injections., Methods: This was an unblinded, prospective randomized control trial with a crossover design where each patient received transcutaneous transcricothyroid injection of botulinum toxin with alternating use of no anesthesia, local anesthesia (2% lidocaine in 1:100,000 epinephrine), and vibrating instrument in three consecutive laryngeal injections to treat adductor SD. Patients were randomized to the order they received these treatments. Patients measured pain on a 0-10 visual analogue scale (VAS) and selected their preferred technique after receiving all three analgesic modalities., Results: Thirty-two patients completed the study. There was no statistically significant difference in pain between the three analgesic techniques (p = 0.38). The most preferred analgesic technique was the vibrating wand (44% (14/32)). Lidocaine was the second most preferred (37% (12/32)) and 19% (6/32) of patients preferred nothing. When combining the wand and nothing groups, 63% of patients preferred one of these two methods (95% exact CI: 44%-79%)., Conclusion: There was no statistically significant difference in median pain experienced by patients during laryngeal botulinum toxin injection between these different analgesic modalities. More than half of the patients selected a preference for a technique that did not include lidocaine. This data supports individualization of analgesia during transcutaneous laryngeal injections., Level of Evidence: 2 Laryngoscope, 134:2277-2281, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Competing Interests: Declaration of Competing Interest The authors wish to declare no competing interests.

Background: Psychosocial factors, such as social support, can reduce pain. Virtual reality (VR) is a powerful tool to decrease pain, but social factors in VR-based pain analgesia have rarely been studied. Specifically, it is unclear whether social support by virtual characters can reduce pain and whether the perceived control behind virtual characters (agency) and varying degrees of social cues impact pain perception., Methods: Healthy participants (N = 97) received heat pain stimulation while undergoing four within-subject conditions in immersive VR: (1) virtual character with a low number of social cues (virtual figure) provided verbal support, (2) virtual character with a high number of social cues (virtual human) provided verbal support, (3) no social support (hearing neutral words), (4) no social support. Perceived agency of the virtual characters served as between-subjects factor. Participants in the avatar group were led to believe that another participant controlled the virtual characters. Participants in the agent group were told they interacted with a computer. However, in both conditions, virtual characters were computer-controlled. Pain ratings, psychophysiological measurements and presence ratings were recorded., Results: Virtual social support decreased pain intensity and pain unpleasantness ratings but had no impact on electrodermal activity nor heart rate. A virtual character with a high number of social cues led to lower pain unpleasantness and higher feelings of presence. Agency had no significant impact., Conclusions: Virtual characters providing social support can reduce pain independent of perceived agency. A more human visual appearance can have beneficial effects on social pain modulation by virtual characters., Significance: Social influences are important factors in pain modulation. The current study demonstrated analgesic effects through verbal support provided by virtual characters and investigated modulating factors. A more human appearance of a virtual character resulted in a higher reduction of pain unpleasantness. Importantly, agency of the virtual characters had no impact. Given the increasing use of digital health interventions, the findings suggest a positive impact of virtual characters for digital pain treatments., (© 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Purpose: Safe and effective analgesia sub partu is one of the central issues in optimizing vaginal delivery birth experiences. Meptazinol is a common opiate approved for treating labor pain in the first stage of labor. According to the manufacturer, manual meptazinol can be applied intramuscularly or intravenously. The aim of this study was to compare the two application methods in terms of efficacy in pain relief, occurrence of side effects and treatment satisfaction., Methods: 132 patients with singleton term pregnancies and intended vaginal delivery, receiving meptazinol during first stage of labor were included in this prospective cohort study from 05/2020 to 01/2021. We evaluated effectiveness in pain relief and treatment satisfaction using numeric rating scales (NRS) and documented the occurrence of adverse effects. Chi-square test or Fisher exact test were used to compare categorical data and Mann-Whitney U test to compare continuous data between the two treatment groups. Statistical analysis was done by SPSS 27.0. A p value < 0.05 was considered to indicate statistical significance (two tailed)., Results: Meptazinol decreased labor pain significantly from a NRS of 8 (IQR 8-10) to 6 (IQR 4.75-8) in both treatment groups with no difference in effectiveness between the groups. Frequency of effective pain reduction of a decrease of 2 or more on the NRS did not differ between groups (39.4% vs 54.5%, p = 0.116), as the occurrence of adverse effects. 12% of the newborns were admitted to NICU, the median NApH was 7.195., Conclusion: Meptazinol significantly reduces labor pain regardless of the method of application: intramuscular or intravenous. According to our data, no preferable route could be identified. The comparably poorer perinatal outcome in our study cohort hinders us to confirm that meptazinol is safe and can be recommended without restrictions., (© 2023. The Author(s).)

Background: Open-label placebos (OLP) prescribed without deception and with a convincing rationale have been shown to evoke powerful treatment effects. Patients' treatment expectations seem to influence the magnitude of the effect., Objective: We examined if two different OLP rationales increased pain tolerance and reduced pain intensity and unpleasantness in a standardized heat pain experiment., Methods: Participants (N = 71) who self-reported reoccurring pain for at least the last 3 months were randomly assigned to one of three groups. We compared a personal-emotional and a scientific-matter-of-fact rationale with a control group (CG) that received the same placebo without any rationale. The rationale suggested a desensitizing effect on pain perception and improved pain coping of the placebo, whereas in the CG it was introduced as an ointment for measurement. The primary outcomes were pre-post changes in pain tolerance, expected and experienced pain intensity and unpleasantness., Results: Participants showed a decrease in expected pain intensity, but not expected pain unpleasantness for both rationales. There were no differences in pain tolerance and experienced pain intensity and unpleasantness., Conclusions: Our study suggests that evoking positive treatment expectations is not sufficient to elicit an OLP response. Possibly, the magnitude of expectations change in this study was not powerful enough to evoke an OLP effect. Additionally, it is possible that OLP effects in pain are unrelated to positive treatment expectations. The failure of OLP in our study is in contrast to a number of previous studies examining the effects of OLP in experimental and clinical pain., Significance: This study provides evidence that positive treatment expectations are not sufficient to evoke an open-label placebo effect in a standardized heat pain experiment. We showed that two different rationales improved participants treatment expectations, but failed to evoke a placebo effect in comparison to a control group that received the same placebo, labelled as an ointment to improve measurement quality., (© 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

A novel microparticle-based extended-release local anaesthetic containing a bupivacaine/poly-lactic-co-glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first-in-human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose-ascending manner (150- to 600-mg bupivacaine). Subjects were admitted 24 h post-injection and followed for 30 days post-injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81-52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69-9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52-8.16; P = 0.004) and 4.00 (0.72-24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4-13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600-mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post-injection) coinciding with plasma peak bupivacaine concentrations (490-533 ng/ml). Both LIQ865 formulations demonstrated dose-dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications., (© 2024 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Neuropeptide FF (NPFF) plays a critical role in various physiological processes through the activation of neuropeptide FF receptor 1 and 2 (NPFFR1 and NPFFR2). Numerous evidence has indicated that NPFF exhibits opposite opioid-modulating effects on opioid-induced analgesia after supraspinal and spinal administrations, while the detailed role of NPFFR1 and NPFFR2 remains unclear. In this study, we employed pharmacological and genetic inhibition of NPFFR to investigate the modulating roles of central NPFFR1 and NPFFR2 in opioid-induced analgesia and hyperalgesia, using a male mouse model of acute fentanyl-induced analgesia and secondary hyperalgesia. Our findings revealed that intrathecal (i.t.) injection of the nonselective NPFFR antagonist RF9 significantly enhanced fentanyl-induced analgesia, whereas intracerebroventricular (i.c.v.) injection did not show the same effect. Moreover, NPFFR2 deficient (npffr2 -/- ) mice exhibited stronger analgesic responses to fentanyl compared to wild type (WT) or NPFFR1 knockout (npffr1 -/- ) mice. Intrathecal injection of RF9 in npffr1 -/- mice also significantly enhanced fentanyl-induced analgesia. These results indicate a crucial role of spinal NPFFR2 in the enhancement of opioid analgesia. Contrastingly, hyperalgesia induced by fentanyl was markedly reversed in npffr1 -/- mice but remained unaffected in npffr2 -/- mice. Similarly, i.c.v. injection of the selective NPFFR1 antagonist RF3286 effectively prevented fentanyl-induced hyperalgesia in WT or npffr2 -/- mice. Notably, co-administration of i.c.v. RF3286 and i.t. RF9 augmented fentanyl-induced analgesia while reducing hyperalgesia. Collectively, these findings highlight the modulating effects of blocking spinal NPFFR2 and supraspinal NPFFR1 on fentanyl-induced analgesia and hyperalgesia, respectively, which shed a light on understanding the pharmacological function of NPFF system in future studies., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Video-assisted thoracic surgery (VATS) is currently used for the repair of pectus excavatum. Analgesia after thoracic surgery can be provided with nerve blocks, intravenous drugs, or neuraxial techniques. Serratus posterior superior intercostal plane block (SPSIPB) is a novel interfascial plane block and it is performed between the serratus posterior superior muscle and the intercostal muscles at the level of the second and third ribs. In this case, we present our successful analgesic experience with SPSIPB in a patient who underwent minimally invasive pectus excavatum repair with a VATS technique., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

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., (© 2024 Wiley Periodicals LLC.)

Background: Comfort evaluation is one of the major challenges in the palliative care setting, particularly when it comes to non-communicative patients. For this specific population, validated tools for comfort evaluation are scarce and healthcare professionals have to rely on their clinical sense and experience. Objectives: To provide arguments for the use of Analgesia/Nociception Index (ANI) monitoring in order to improve clinical comfort evaluation. Methods: We conducted a retrospective cohort study of non-communicative patients at the end of their lives whose comfort was evaluated clinically and with ANI. We focused on the coherence or discordance of clinical and ANI evaluations and on pharmacological interventions driven by them. Results: 58 evaluations from 33 patients were analyzed. Clinical and demographic characteristics were highly variable. Simultaneous clinical and ANI evaluations were concordant in 45 measurements (77.58%), leading mostly to no treatment modification when indicating comfort and to increasing anxiolytic or pain-relief treatments when indicating discomfort. Thirteen (22.41%) evaluations were discordant, leading mostly to treatment incrementation. Conclusion: We suggest that the ANI monitor is a reliable tool in the palliative setting and may help provide patients with the best symptom relief and the most appropriate therapeutics.

The extensive use of opioids for chronic pain management has contributed significantly to the current opioid epidemic. While many alternative nonopioid analgesics are available, opioids remain the most potent analgesics for moderate to severe pain management. In addition to the implementation of multimodal analgesia, there is a pressing need for the development of more effective and safer opioids. In this study, we developed a thermoresponsive N -(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based hydromorphone (HMP) prodrug (ProGel-HMP, HMP content = 16.2 wt %, in base form). The aqueous solution of ProGel-HMP was free-flowing at 4 °C but became a hydrogel when the temperature was raised to ≥37 °C, allowing sustained local retention when administered in vivo . When tested in the destabilization of the medial meniscus (DMM) mouse model of osteoarthritis (OA), ProGel-HMP was retained after intra-articular injection in the OA knee joint for at least 2 weeks postinjection, with low extra-articular distribution. ProGel-HMP was not detected in the central nervous system (CNS). A single dose of ProGel-HMP produced rapid and sustained joint pain resolution for greater than 14 days when compared to saline and dose-equivalent HMP controls, likely mediated through peripheral μ-opioid receptors in the knee joint. Systemic analgesia effect was absent in the DMM mice treated with ProGel-HMP, as evident in the lack of difference in tail flick response between the ProGel-HMP-treated mice and the controls ( i.e ., Healthy, Saline, and Sham). Repeated dosing of ProGel-HMP did not induce tolerance. Collectively, these data support the further development of ProGel-HMP as a potent, safe, long-acting and nonaddictive analgesic for better clinical pain management.

Background: The effect of analgesic modalities on short-term outcomes in acute pancreatitis remains unknown. However, preclinical models have raised safety concerns regarding opioid use in patients with acute pancreatitis., Objective: This study aimed to assess the association between analgesics, particularly opioids, and severity and mortality in hospitalised patients with acute pancreatitis., Methods: This prospective multicentre cohort study recruited consecutive patients admitted with a first episode of acute pancreatitis between April 1 and 30 June 2022, with a 1-month follow-up. Data on aetiology, clinical course, and analgesic treatment were collected. The primary outcome was the association between opioid analgesia and acute pancreatitis severity, which was analysed using univariate and multivariate analyses., Results: Among a total of 1768 patients, included from 118 centres across 27 countries, 1036 (59%) had opioids administered on admission day, and 167 (9%) received opioids after admission day. On univariate analysis, moderately severe or severe acute pancreatitis was associated with male sex, Asian ethnicity, alcohol aetiology, comorbidity, predicted severe acute pancreatitis, higher pain scores, longer pain duration and opioid treatment (all p < 0.001). On multivariate analysis, comorbidity, alcohol aetiology, longer pain duration and higher pain scores increased the risk of moderately severe or severe acute pancreatitis (all p < 0.001). Furthermore, opioids administered after admission day (but not on admission day) doubled the risk of moderately severe or severe disease (OR 2.07 (95% CI, 1.29-3.33); p = 0.003). Opioid treatment for 6 days or more was an independent risk factor for moderately severe or severe acute pancreatitis (OR 3.21 (95% CI, 2.16-4.79; p < 0.001). On univariate analysis, longer opioid duration was associated with mortality., Conclusion: Opioid treatment increased the risk of more severe acute pancreatitis only when administered after admission day or for 6 days or more. Future randomised studies should re-evaluate whether opioids might be safe in acute pancreatitis., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Few studies have evaluated the use of automated artificial intelligence (AI)-based pain recognition in postoperative settings or the correlation with pain intensity. In this study, various machine learning (ML)-based models using facial expressions, the analgesia nociception index (ANI), and vital signs were developed to predict postoperative pain intensity, and their performances for predicting severe postoperative pain were compared., Methods: In total, 155 facial expressions from patients who underwent gastrectomy were recorded postoperatively; one blinded anesthesiologist simultaneously recorded the ANI score, vital signs, and patient self-assessed pain intensity based on the 11-point numerical rating scale (NRS). The ML models' area under the receiver operating characteristic curves (AUROCs) were calculated and compared using DeLong's test., Results: ML models were constructed using facial expressions, ANI, vital signs, and different combinations of the three datasets. The ML model constructed using facial expressions best predicted an NRS ≥ 7 (AUROC 0.93) followed by the ML model combining facial expressions and vital signs (AUROC 0.84) in the test-set. ML models constructed using combined physiological signals (vital signs, ANI) performed better than models based on individual parameters for predicting NRS ≥ 7, although the AUROCs were inferior to those of the ML model based on facial expressions (all P < 0.050). Among these parameters, absolute and relative ANI had the worst AUROCs (0.69 and 0.68, respectively) for predicting NRS ≥ 7., Conclusions: The ML model constructed using facial expressions best predicted severe postoperative pain (NRS ≥ 7) and outperformed models constructed from physiological signals.

Background: The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain., Methods: Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents., Results: The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling., Conclusions: Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Chronic pain conditions are unmet medical needs, since the available drugs, opioids, non-steroidal anti-inflammatory/analgesic drugs and adjuvant analgesics do not provide satisfactory therapeutic effect in a great proportion of patients. Therefore, there is an urgent need to find novel targets and novel therapeutic approaches that differ from classical pharmacological receptor antagonism. Most ion channels and receptors involved in pain sensation and processing such as Transient Receptor Potential ion channels, opioid receptors, P2X purinoreceptors and neurokinin 1 receptor are located in the lipid raft regions of the plasma membrane. Targeting the membrane lipid composition and structure by sphingolipid or cholesterol depletion might open future perspectives for the therapy of chronic inflammatory, neuropathic or cancer pain, most importantly acting at the periphery., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h 2  = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h 2  = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia., (© 2024 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Purpose: Rib fracture(s) is a common and painful injury often associated with significant morbidity (e.g., respiratory complications) and high mortality rates, especially in the elderly. Risk stratification and prompt implementation of analgesic pathways using a multimodal analgesia approach comprise a primary endpoint of care to reduce morbidity and mortality associated with rib fractures. This narrative review aims to describe the most recent evidence and care pathways currently available, including risk stratification tools and pharmacologic and regional analgesic blocks frequently used as part of the broadly recommended multimodal analgesic approach., Source: Available literature was searched using PubMed and Embase databases for each topic addressed herein and reviewed by content experts., Principal Findings: Four risk stratification tools were identified, with the Study of the Management of Blunt Chest Wall Trauma score as most predictive. Current evidence on pharmacologic (i.e., acetaminophen, nonsteroidal anti-inflammatory drugs, gabapentinoids, ketamine, lidocaine, and dexmedetomidine) and regional analgesia (i.e., thoracic epidural analgesia, thoracic paravertebral block, erector spinae plane block, and serratus anterior plane block) techniques was reviewed, as was the pathophysiology of rib fracture(s) and its associated complications, including the development of chronic pain and disabilities., Conclusion: Rib fracture(s) continues to be a serious diagnosis, with high rates of mortality, development of chronic pain, and disability. A multidisciplinary approach to management, combined with appropriate analgesia and adherence to care bundles/protocols, has been shown to decrease morbidity and mortality. Most of the risk-stratifying care pathways identified perform poorly in predicting mortality and complications after rib fracture(s)., (© 2024. Canadian Anesthesiologists' Society.)

Abstract: Sternal wound complications following sternotomy need a multidisciplinary approach in high-risk postoperative cardiac surgical patients. Poorly controlled pain during surgical management of such wounds increases cardiovascular stress and respiratory complications. Multimodal analgesia including intravenous opioids, non-opioid analgesics, and regional anesthesia techniques, like central neuraxial blocks and fascial plane blocks, have been described. Pecto-intercostal fascial plane block (PIFB), a novel technique, has been effectively used in patients undergoing cardiac surgery. Under ultrasound (US) guidance PIFB is performed with the aim of depositing local anesthetic between two superficial muscles, namely the pectoralis major muscle and the external intercostal muscle. The authors report a series of five cases where US-guided bilateral PIFB was used in patients undergoing sternal wound debridement. Patients had excellent analgesia intraoperatively as well as postoperatively for 24 hours with minimal requirement of supplemental analgesia. None of the patients experienced complications due to PIFB administration. The authors concluded that bilateral PIFB can be effectively used as an adjunct to multimodal analgesia with general anesthesia and as a sole anesthesia technique in selected cases of sternal wound debridement., (Copyright © 2024 Copyright: © 2024 Annals of Cardiac Anaesthesia.)

Although laboratory studies indicate alcohol reduces pain intensity and increases pain threshold, these effects likely do not completely explain perceived pain relief from alcohol intake. In this study, we tested expectancy of alcohol analgesia (EAA) as a moderator of subjective pain relief following oral alcohol challenge in individuals with and without chronic orofacial pain. Social drinkers ( N = 48; 19 chronic pain; 29 pain-free controls) completed two testing sessions: alcohol administration (BrAC: 0.08 g/dL) and placebo. Alcohol expectancy (AE) was assessed using the EAA questionnaire and two 100-mm Visual Analogue Scales (VASs) regarding strength of belief that alcohol provides pain relief (AE VAS 1) or reduces pain sensitivity (AE VAS 2). Participants completed quantitative sensory testing (QST) involving application of pressure to the masseter insertion. Pain threshold (lbf; three repetitions) and pain intensity (4, 5, and 6 lbf; three repetitions each; 100-mm VAS) were collected. After each stimulus, participants rated perceived pain relief due to consumption of the study beverage (0-100 VAS). Higher EAA and AE VAS 1 ratings were associated with stronger perceived relief in the alcohol, but not placebo, condition. However, expectancy specifically related to reduction in pain sensitivity (AE VAS 2) was not associated with relief. Additionally, changes in pain threshold and intensity were not significantly correlated with perceived relief. Taken together, results suggest expectancy that alcohol provides pain relief is an important determinant of its negative reinforcing effects. Future studies should investigate challenging these expectancies as a means of reducing alcohol-related risk in people with pain. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Competing Interests: The author has declared that there are no conflicts of interest.

Purpose: The study was conducted to determine the effect of preoperative pain, fear, and anxiety on postoperative pain and analgesia use in urology patients., Design: A descriptive and correlational design was used., Methods: The population of the study consisted of patients who were hospitalized in the Urology clinic of a university hospital and were planning surgery. The sample consisted of 106 patients who met the inclusion criteria and agreed to participate in the study. The study's data was collected using the Personal Information Form, Analgesia Follow-up Form, Surgical Fear Questionnaire, Surgical Anxiety Questionnaire, and Visual Analog Scale prepared in line with the literature. Descriptive statistics, Pearson correlation coefficient, and linear regression analysis were used to evaluate the data., Findings: A positive linear relationship was found between postoperative pain and surgical anxiety, surgical fear, and preoperative pain (P < .05). Regression analysis revealed that preoperative pain (P = .006) affected the level of postoperative pain. In addition, fear of surgery (P = .035) and postoperative pain (P = .000) were found to affect the use of postoperative 24-hour analgesia., Conclusions: The study revealed a relationship between the postoperative pain experienced by the patients and preoperative pain, fear, and anxiety., Competing Interests: Declaration of Competing Interest None to report., (Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background/Objective: Pediatric intensive care unit (PICU) survivors risk significant cognitive morbidity, particularly those with acquired brain injury (ABI) diagnoses. Studies show sedative and analgesic medication may potentiate neurologic injury, but few studies evaluate impact on survivor outcomes. This study aimed to evaluate whether exposures to analgesic and sedative medications are associated with worse neurocognitive outcome. Methods: A retrospective cohort study was conducted of 91 patients aged 8 to 18 years, undergoing clinical neurocognitive evaluation approximately 1 to 3 months after PICU discharge. Electronic health data was queried for sedative and analgesic medication exposures, including opioids, benzodiazepines, propofol, ketamine, and dexmedetomidine. Doses were converted to class equivalents, evaluated by any exposure and cumulative dose exposure per patient weight. Cognitive outcome was derived from 8 objective cognitive assessments with an emphasis on executive function skills using Principal Components Analysis. Then, linear regression was used to control for baseline cognitive function estimates to calculate a standardized residualized neurocognitive index (rNCI) z -score. Multivariable linear regression evaluated the association between rNCI and medication exposure controlling for covariates. Significance was defined as P  < .05. Results: Most ( n  = 80; 88%) patients received 1 or more study medications. Any exposure and higher cumulative doses of benzodiazepine and ketamine were significantly associated with worse rNCI in bivariate analyses. When controlling for Medicaid, preadmission comorbid conditions, length of stay, delirium, and receipt of other medication classes, receipt of benzodiazepine was associated with significantly worse rNCI ( β -coefficient = -0.48, 95% confidence interval = -0.88, -0.08). Conclusions: Exposure to benzodiazepines was independently associated with worse acute phase cognitive outcome using objective assessments focused on executive function skills when controlling for demographic and illness characteristics. Clinician decisions regarding medication regimens in the PICU may serve as a modifiable factor to improve outcomes. Additional inquiry into associations with long-term cognitive outcome and optimal medication regimens is needed., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The number of patients with chronic pain continues to increase against the background of an ageing society and a high incidence of various epidemics and disasters. One factor contributing to this situation is the absence of truly effective analgesics. Chronic pain is a persistent stress for the organism and can trigger a variety of neuropsychiatric symptoms. Hence, the search for useful analgesic targets is currently being intensified worldwide, and it is anticipated that the key to success may be molecules involved in emotional as well as sensory systems. High mobility group box-1 (HMGB1) has attracted attention as a therapeutic target for a variety of diseases. It is a very unique molecule having a dual role as a nuclear protein while also functioning as an inflammatory agent outside the cell. In recent years, numerous studies have shown that HMGB1 acts as a pain inducer in primary sensory nerves and the spinal dorsal horn. In addition, HMGB1 can function in the brain, and is involved in the symptoms of depression, anxiety and cognitive dysfunction that accompany chronic pain. In this review, we will summarize recent research and discuss the potential of HMGB1 as a useful drug target for chronic pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Accumulating evidence supports the notion that microglia play versatile roles in different chronic pain conditions. However, therapeutic strategies of chronic pain by targeting microglia remain largely overlooked. This study seeks to develop a miRNA-loaded nano-delivery system by targeting microglia, which could provide a decent and long-lasting analgesia for chronic pain. Surface aminated mesoporous silica nanoparticles were adopted to load miR-26a-5p, a potent analgesic miRNA, by electrostatic adsorption, which can avoid miR-26a-5p is rapidly released and degraded. Then, targeting peptide MG1 was modified on the surface of aminated mesoporous silica particles for microglia targeting. In peripheral nerve injury induced neuropathic pain model, a satisfactory anti-allodynia effect with about 6 weeks pain-relief duration were achieved through targeting microglia strategy, which decreased microglia activation and inflammation by Wnt5a, a non-canonical Wnt pathway. In inflammatory pain and chemotherapy induced peripheral neuropathic pain, microglia targeting strategy also exhibited more efficient analgesia and longer pain-relief duration than others. Overall, we developed a microglia-targeting nano-delivery system, which facilitates precisely miR-26a-5p delivery to enhance analgesic effect and duration for several chronic pain conditions., (© 2024. The Author(s).)

Scapulothoracic arthrodesis (STA) surgery is performed to stabilize the scapula in patients with facioscapulohumeral dystrophy (FSHD). Postoperative pain could be a major problem even while using erector spinae plane block (ESPB). We performed a preoperative ESPB with an intraoperative ESPB catheter, but rescue analgesia was needed for pain in the periscapular area in the postoperative period. The patient's pain score was reduced by applying an ultrasound-guided dorsal scapular nerve (DSN) and long thoracic nerve (LTN) block. Selective DSN and LTN blocks can be effective in enhancing postoperative analgesia in STA surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs . 4.0 (3.0, 5.0)] ( Z =-3.73, P <0.001), 6 h [2.0 (1.0, 4.0) vs . 5.0(2.5, 6.0)] ( Z =-3.38, P <0.001), and 8 h [2.0 (1.0, 4.0) vs . 5.0 (2.0, 6.0)] ( Z =-2.11, P =0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P >0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs . 1.0 (0.0, 3.0)] ( Z =-2.81, P =0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Purpose: The objective of this study was to perform a retrospective cohort analysis, in which we measured the association of an acute pain service (APS)-driven multimodal analgesia protocol that included preoperative intrathecal morphine (ITM) compared to historic controls (i.e., surgeon-driven analgesia protocol without ITM) with postoperative opioid use., Methods: This was a retrospective cohort study in which the primary objective was to determine whether there was a decrease in median 24-h opioid consumption (intravenous morphine equivalents [MEQ]) among robotic nephrectomy patients whose pain was managed by the surgical team prior to the APS, versus pain managed by APS. Secondary outcomes included opioid consumption during the 24-48 h and 48-72 h period and hospital length of stay. To create matched cohorts, we performed 1:1 (APS:non-APS) propensity score matching. Due to the cohorts occurring at the different time periods, we performed a segmented regression analysis of an interrupted time series., Results: There were 76 patients in the propensity-matched cohorts, in which 38 (50.0%) were in the APS cohort. The median difference in 24-h opioid consumption in the pre-APS versus APS cohort was 23.0 mg [95% CI 15.0, 31.0] (p < 0.0001), in favor of APS. There were no differences in the secondary outcomes. On segmented regression, there was a statistically significant drop in 24-h opioid consumption in the APS cohort versus pre-APS cohort (p = 0.005)., Conclusions: The implementation of an APS-driven multimodal analgesia protocol with ITM demonstrated a beneficial association with postoperative 24-h opioid consumption following robot-assisted nephrectomy., (© 2024. The Author(s).)

Background: Procedural sedation and analgesia are commonly used in the Emergency Departments. Despite this common need, there is still a lack of options for adequate and safe analgesia and sedation in children. The objective of this study was to evaluate whether intranasal dexmedetomidine could provide more effective analgesia and sedation during a procedure than intranasal esketamine., Methods: This was a double-blind equally randomized (1:1) superiority trial of 30 children aged 1-3 years presenting to the Emergency Department with a laceration or a burn and requiring procedural sedation and analgesia. Patients were randomized to receive 2.0 mcg/kg intranasal dexmedetomidine or 1.0 mg/kg intranasal esketamine. The primary outcome measure was highest pain (assessed using Face, Legs, Activity, Cry, Consolability scale (FLACC)) during the procedure. Secondary outcomes were sedation depth, parents' satisfaction, and physician's assessment. Comparisons were done using Mann-Whitney U test (continuous variables) and Fisher's test (categorical variables)., Results: Adequate analgesia and sedation were reached in 28/30 patients. The estimated sample size was not reached due to changes in treatment of minor injuries and logistical reasons. The median (IQR) of highest FLACC was 1 (0-3) with intranasal dexmedetomidine and 5 (2-6.75) with intranasal esketamine, (p-value 0.09). 85.7% of the parents with children treated with intranasal dexmedetomidine were "very satisfied" with the procedure and sedation compared to the 46.2% of those with intranasal esketamine, (p-value 0.1). No severe adverse events were reported during this trial., Conclusions: This study was underpowered and did not show any difference between intranasal dexmedetomidine and intranasal esketamine for procedural sedation and analgesia in young children. However, the results support that intranasal dexmedetomidine could provide effective analgesia and sedation during procedures in young children aged 1-3 years with minor injuries., Trial Registration: Eudra-CT 2017-00057-40, April 20, 2017. https://eudract.ema.europa.eu/., (© 2024. The Author(s).)

Although nitrous oxide is widely used for analgesia and anxiolysis, its use is under scrutiny because of concerns about its environmental impact and potential implications for mental health. This article discusses the advantages and disadvantages of this agent.

Ovariohysterectomy (OVH) is a widely used surgical procedure in small animal practice. In developing countries, injectable anesthetics such as ketamine and xylazine are commonly used in veterinary medicine. Pharmacological agents with analgesic activity, such as ketamine and meloxicam, are not sufficiently effective in reducing visceral pain. Therefore, this study aimed to investigate the visceral analgesia and anti-inflammatory effectiveness of maropitant compared with those of meloxicam during and after OVH in bitches. In this study, thirty-six bitches were randomly divided into the maropitant, meloxicam, and control groups. The heart rate (HR), peripheral oxygen saturation, and respiratory rate were monitored during the procedure. Pain scores were assessed using the University of Melbourne pain scale (UMPS). Rescue analgesia was not necessary for any bitch at any time point. Blood samples were collected before anesthesia induction and 24 h after the operation to determine C-reactive protein (CRP) levels. No significant difference was observed in HR between the control and meloxicam groups when the right ovary was removed, and the HR of the maropitant group was significantly (p < 0.05) lower than that of the control group. The pain scores of the maropitant group were significantly (p < 0.05) lower than those of the other groups. However, no significant differences were observed in CRP levels between the groups. In conclusion, compared to meloxicam, maropitant provided more effective visceral analgesia in bitches undergoing OVH, although no significant difference was found in its anti-inflammatory effect., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

The major goal of translational research is to evaluate the efficacy and effectiveness of treatments and interventions that have emerged from exhaustive preclinical evidence. In 2007, a major clinical trial was started to investigate the impact of paravertebral analgesia on breast cancer recurrence. The trial was based on preclinical evidence demonstrating that spinal anesthesia suppressed metastatic dissemination by inhibiting surgical stress, boosting the immunological response, avoiding volatile anesthetics, and reducing opioid use. However, that trial and three more recent randomized trials with a total of 4,770 patients demonstrate that regional analgesia does not improve survival outcomes after breast, lung, and abdominal cancers. An obvious question is why there was an almost complete disconnect between the copious preclinical investigations suggesting benefit and robust clinical trials showing no benefit? The answer is complex but may result from preclinical research being mechanistically driven and based on reductionist models. Both basic scientists and clinical investigators underestimated the limitations of various preclinical models, leading to the apparently incorrect hypothesis that regional anesthesia reduces cancer recurrence. This article reviews factors that contributed to the discordance between the laboratory science, suggesting that regional analgesia might reduce cancer recurrence and clinical trials showing that it does not-and what can be learned from the disconnect., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

SYNOPSIS: Understanding the descending pain modulatory system allows for a neuroscientific explanation of naturally occurring pain relief. Evidence from basic science and clinical studies on the effectiveness of drugs in certain patient groups led to pharmacological manipulation of the descending pain modulatory system for analgesia. Understanding mechanisms and theories helps clinicians make sense of chronic musculoskeletal pain. This editorial explains how test paradigms, including conditioned pain modulation, offset analgesia, and stress-induced analgesia work, provide an overview of a placebo analgesia circuitry, and discusses how evoking activity in the descending pain modulatory system using specific paradigms can give new insights into how specific treatments work to reduce pain. J Orthop Sports Phys Ther 2024;54(2):1-6. doi:10.2519/jospt.2024.12113 .

Objective: To perform a qualitative evaluation of the analgesic effects of magnesium in domestic animals, including its anaesthetic sparing effects., Study Design: All database searches were made using PubMed and Google Scholar. Studies published after 1990, evaluating the use of magnesium and reporting information on analgesia, in dogs, cats, horses, cows, goats and sheep were selected (last search in August 2023). A reference check in the selected papers was performed to identify any study which was omitted. The CERQual (Confidence in Evidence from Reviews of Qualitative research) approach was used to assess confidence and analyse the evidence., Results: A total of 20 studies relevant to the analgesic effects of magnesium in veterinary patients and two reviews were included. All were published after 2006. Of the 20, five studies provided information about analgesia in the postoperative period in dogs with heterogenous results. Magnesium added epidurally increased the duration of the sensory block in several species. Motor block was also observed when added to spinal analgesia. Results regarding volatile agents sparing effect were conflicting. Occasional moderate adverse effects were reported in dogs, such as nausea and vomiting, when administered as a bolus in conscious animals, and hypotension when administered intraperitoneally. Collapse was reported in horses after epidural administration., Conclusions and Clinical Relevance: The evidence of an analgesic effect of magnesium in veterinary patients remains scarce considering the paucity and low quality of published data. Further research may be helpful to establish the efficacy and indications of magnesium in multimodal analgesia in animals., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: Acute pancreatitis is one of the main reasons for digestive admissions. Adequate pain treatment is crucial in its management. However, there are hardly any descriptions of the analgesic guidelines used in our setting., Methods: On-line survey on analgesic management in acute pancreatitis, aimed at attending physicians and residents practising in Spain., Results: Two hundred and nine physicians from 88 centres responded to the survey. Ninety percent were specialists in gastrointestinal medicine and 69% worked in a tertiary centre. The majority (64.4%) do not routinely use scales to measure pain. When choosing a drug, experience in its use was the most important factor. The most commonly prescribed initial treatments are: combination of paracetamol and metamizole (53.5%), paracetamol alone (19.1%) and metamizole alone (17.4%). As rescue: meperidine (54.8%), tramadol (17.8%), morphine chloride (17.8%) and metamizole (11.5%). Continuous perfusion is used in 8.2% of initial treatments. Physicians with >10 years of service use more metamizole as monotherapy (50%), while residents and attending physicians with <10 years of service prescribe it in combination with paracetamol (85%). If progression is needed, morphine chloride and meperidine are mainly used. The speciality of the respondent, the size of the work centre and the unit/service where the patients were admitted did not influence the analgesia prescribed. Satisfaction with pain management reached 7.8/10 (SD 0.98)., Conclusion: In our setting, metamizole and paracetamol are the most commonly used analgesics as initial pain treatment in acute pancreatitis, and meperidine is the most commonly used rescue analgesic., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Objective: To compare the efficacy of preemptive ibuprofen, local ketamine, and their combination in managing postoperative pain and trismus following third molar surgery., Materials and Methods: One hundred patients were randomly divided into 4 groups. The Intrafen Group had their impacted third molars surgically removed under local anesthesia after receiving intravenous (IV) ibuprofen for preemptive effect. The Ketamine Group received an IV placebo before the surgery, and the extraction process was completed with a local anesthetic-ketamine combination. The Combined Group received preemptive IV ibuprofen before the procedure, and the surgery was performed with a local anesthetic-ketamine combination. The Control Group received an IV placebo before the procedure and then had their impacted third molars removed under local anesthesia. The Visual Analogue Scale (VAS) values, corresponding to the patients' pain levels at the 2nd and 12th postoperative hours and the total amount of analgesic dose used in the first 24 hours, were recorded, and evaluated. The maximum mouth opening of the patients was measured immediately before the procedure, and on the second and seventh postoperative days. The level of patient satisfaction in all groups was assessed during the procedure., Results: The mean VAS value corresponding to the second-hour pain level of the combined group was statistically significantly lower than the other groups (P = .003). A statistically significant difference was found in the mean VAS values corresponding to the pain levels of the groups, favoring the combined group compared to the other groups (P ≤ .001). A significant difference was observed between the VAS difference values corresponding to the pain levels of the Intrafen group and the Ketamine group, favoring the Intrafen group (P = .038). The Ketamine group consumed the most analgesic on average over the first 24 hours, whereas the Combined group consumed the least. No statistically significant difference was found between the mean trismus levels of the groups on days 0-2 (P = .528) and days 0-7 (P = .129). The intraoperative patient satisfaction level of the combined group was significantly higher than that of the other groups (P = .030)., Conclusion: Preemptive Intrafen is an effective regimen for postoperative pain management and is superior to the local anesthetic-ketamine regimen. The most effective method to reduce postoperative pain following third molar surgery is to use a combination of these 2 regimens. However, none of the treatment methods used in the study had a positive effect on postoperative trismus., (Copyright © 2023 Elsevier Inc. All rights reserved.)