High uptake of menstrual health information, products and analgesics within an integrated sexual reproductive health service for young people in Zimbabwe.

BACKGROUND: Despite being integral to women's well-being, achieving good menstrual health (MH) remains a challenge. This study examined MH services uptake (including information, analgesics, and a choice of MH products - the menstrual cup and reusable pads) and sustained use of MH products within an integrated sexual and reproductive health intervention for young people in Zimbabwe. METHODS: This mixed-methods study was nested within a cluster randomised trial of integrated sexual and reproductive health services (CHIEDZA) for youth in three provinces (Harare, Mashonaland East, and Bulawayo). The study collected qualitative and quantitative data from 27,725 female clients aged 16-24 years, who accessed CHIEDZA from April 2019 - March 2022. Using a biometric (fingerprint recognition) identification system, known as SIMPRINTS, uptake of MH information, products, and analgesics and other services was tracked for each client. Descriptive statistics and logistic regression were used to investigate MH service uptake and product choice and use over time, and the factors associated with these outcomes. Thematic analysis of focus group discussions and interviews were used to further explore providers' and participants' experiences of the MH service and CHIEDZA intervention. RESULTS: Overall, 36,991 clients accessed CHIEDZA of whom 27,725 (75%) were female. Almost all (n = 26,448; 95.4%) took up the MH service at least once: 25433 took up an MH product with the majority (23,346; 92.8%) choosing reusable pads. The uptake of cups varied across province with Bulawayo province having the highest uptake (13.4%). Clients aged 20-24 years old were more likely to choose cups than reusable pads compared with those aged 16-19 years (9.4% vs 6.0%; p < 0.001). Over the implementation period, 300/1819 (16.5%) of clients swapped from the menstrual cup to reusable pads and 83/23346 (0.4%) swapped from reusable pads to the menstrual cup. Provision of the MH service encouraged uptake of other important SRH services. Qualitative findings highlighted the provision of free integrated SRH and MH services that included a choice of MH products and analgesics in a youth-friendly environment were key to high uptake and overall female engagement with SRH services. CONCLUSIONS: High uptake demonstrates how the MH service provided much needed access to MH products and information. Integration of MH within an SRH intervention proved central to young women accessing other SRH services.

The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis.

OBJECTIVES: To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. BACKGROUND: Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear. METHODS: Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096). RESULTS: A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics. CONCLUSIONS: Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.

Manejo de la analgesia en la pancreatitis aguda. Resultados de una encuesta nacional / Management of analgesia in acute pancreatitis: Results of a national survey

Introducción La pancreatitis aguda constituye uno de los principales motivos de ingreso por causa digestiva. En su manejo resulta crucial un adecuado tratamiento del dolor. Pero apenas existen descripciones sobre las pautas analgésicas empleadas en nuestro medio. Métodos Encuesta on-line sobre el manejo de analgésicos en la pancreatitis aguda, dirigida a médicos adjuntos y residentes con ejercicio en España. Resultados Un total de 209 facultativos de 88 centros respondieron la encuesta. El 90% eran especialistas en Aparato Digestivo y el 69% trabajaba en un centro terciario. La mayoría (64,4%) no utilizan habitualmente escalas para medir el dolor. Al elegir un fármaco se valora sobre todo la experiencia en su uso. Los tratamientos más prescritos inicialmente son: combinación de paracetamol y metamizol (53,5%), paracetamol solo (19,1%) y metamizol solo (17,4%). Como rescate: meperidina (54,8%), tramadol (17,8%), cloruro mórfico (17,8%) y metamizol (11,5%). Se utiliza perfusión continua en el 8,2% de los tratamientos iniciales. Los médicos con >10años de servicio utilizan más metamizol en monoterapia (50%), mientras que médicos residentes y adjuntos con <10años de servicio lo prescriben asociado a paracetamol (85%). Si se necesita progresar, se usan fundamentalmente cloruro mórfico y meperidina. La especialidad del encuestado, el tamaño del centro de trabajo y la unidad/servicio donde ingresaban los pacientes no influyeron sobre la analgesia pautada. El grado de satisfacción con el tratamiento del dolor alcanzó el 7,8/10 (DE 0,98). Conclusión En nuestro medio, el metamizol y el paracetamol son los analgésicos más empleados como tratamiento inicial del dolor en la pancreatitis aguda, y la meperidina, el analgésico de rescate más utilizado (AU)

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. (AU)

Topical Nonprescription Pain Medications for Adults.

This JAMA Patient Page describes the types of topical nonprescription pain medications and tips for using them.

Implicaciones de los diferentes modelos analgésicos en los marcadores inflamatorios tras colecistectomía laparoscópica / Implications of Different Analgesic Models on Inflammatory Markers after Laparoscopic Cholecystectomy

Antecedentes: Las cirugías laparoscópicas inducen dolores de hombro y abdominales significativos, que fluctúan entre 35 y 80% de los pacientes, a pesar de sus ventajas. La causa del dolor posterior a la laparoscopia no se comprende plenamente, suponiéndose que es multifactorial y posiblemente un tipo de dolor referido. Objetivo del estudio Evaluar el efecto de los diferentes modelos analgésicos en el dolor posterior a la laparoscopia y en las modulaciones del marcador inflamatorio. Métodos Se asignó aleatoriamente a los pacientes programados para colecistectomía laparoscópica electiva, para recibir una infiltración local en la fosa hepática y el área subdiafragmática derecha con uno de los cuatro tipos de mezcla analgésica de fármacos siguientes: grupo 1 (G1) con 20 mL de bupivacaína al 0,25%; grupo 2 (G2) con 20 mL de bupivacaína al 0,25% + 3 mg de sulfato de morfina; grupo 3 (G3) con 20 mL de bupivacaína al 0,25% + 3 mg de sulfato de morfina + 200 mcg/kg de ketamina; y grupo 4 (G4) con 20 mL de solución salina isotónica como grupo control. Resultados El G3 demostró unos niveles significativamente bajos en la escala de calificación numérica oral del dolor de hombro y marcadores inflamatorios, en contraste con los tres grupos restantes. Los altos niveles de marcadores inflamatorios, estadísticamente significativos, fueron registrados en el grupo control en la comparación entre los grupos de estudio. No se documentaron efectos secundarios ni complicaciones en los cuatro grupos. Conclusión La adición de ketamina y morfina a bupivacaína para insuflado hepático y subdiafragmático produjo buena analgesia y redujo los niveles de los marcadores inflamatorios tras colecistectomía laparoscópica. (AU)

Background: Despite the advantages of laparoscopic surgeries, its induced shoulder and abdominal pain are significant, ranging from 35% to 80%. The cause of post laparoscopic pain is not fully understood and supposed to be multifactorial and possibly referred to as pain. Aim of the study Evaluate the effect of different analgesic models on post-laparoscopic pain and inflammatory markers modulation. Methods Patients scheduled for elective laparoscopic cholecystectomy randomLy assigned to receive local infiltration of the hepatic and right subdiaphragmatic fossae with one of four types of the analgesic mixture of drugs:-Group-1 (G1): 20 mL of (bupivacaine 0.25%) Group-2 (G2): 20 mL of (bupivacaine 0.25% + 3 mg of Morphine sulphate) Group-3 (G3): 20 mL of (bupivacaine 0.25% + 3 mg of Morphine sulphate + 200 microgram/kg ketamine). Group-4 (G4): 20 mL of isotonic saline as the control group. Results Group 3 demonstrated significant low VNRS of shoulder pain and significantly low levels of inflammatory marker compared with the other three groups. Highest statistically significant levels of inflammatory markers recorded in the control group among the study groups. No side effects or complications documented in the four study groups. Conclusión The addition of Ketamine and Morphine to the Bupivacaine for hepatic and subdiaphragmatic insufflation produced good analgesia and reduced the levels of inflammatory markers after Laparoscopic cholecystectomy. (AU)

Use of analgesics in professional soccer players: A systematic review

Objective: Use of painkillers appears to have become a widespread issue in the sporting environment as athletes pursue successful pain relief during competitions. We conducted a systematic review on the prevalence of analgesics use in soccer, using literature from January 1980 to July 2021. Methods: The systematic review followed PRISMA guidelines. Studies were obtained from the Cochrane Library, PubMed, Scopus, and Web of Science (WOS) databases. In total, 213 articles were found where 14 were selected. The risk of bias was assessed using the NIH scale for prevalence studies and the PEDro quality scale for randomized control trials (RCTs). Results: Less than 3% of the literature were randomized studies (n=10 observational; n=4 double-blind trials) and only 2 studies included females. At least 54% of the research subjects consumed analgesic drugs during the course of their tournaments, and nearly half of them (39-67%) did so before each match, mostly in the form of non-steroidal anti-inflammatory drugs (NSAIDs) (15% of daily use). Conclusion: Given that short-term observational studies indicated high consumption of analgesics despite limited evidence of their pain control effectiveness, the question is raised whether this potential drug abuse affects the sexes at the same rates and in the same ways. Further investigation into these specific cohorts is needed. (AU)

Oral Nonprescription Pain Medications for Adults.

This JAMA Patient Page describes the common oral nonprescription pain medications acetaminophen, aspirin, ibuprofen, and naproxen sodium.

Association of FDA Mandate Limiting Acetaminophen (Paracetamol) in Prescription Combination Opioid Products and Subsequent Hospitalizations and Acute Liver Failure.

Importance: In January 2011, the US Food and Drug Administration (FDA) announced a mandate to limit acetaminophen (paracetamol) to 325 mg/tablet in combination acetaminophen and opioid medications, with manufacturer compliance required by March 2014. Objective: To assess the odds of hospitalization and the proportion of acute liver failure (ALF) cases with acetaminophen and opioid toxicity prior to and after the mandate. Design, Setting, and Participants: This interrupted time-series analysis used hospitalization data from 2007-2019 involving ICD-9/ICD-10 codes consistent with both acetaminophen and opioid toxicity from the National Inpatient Sample (NIS), a large US hospitalization database, and ALF cases from 1998-2019 involving acetaminophen and opioid products from the Acute Liver Failure Study Group (ALFSG), a cohort of 32 US medical centers. For comparison, hospitalizations and ALF cases consistent with acetaminophen toxicity alone were extracted from the NIS and ALFSG. Exposures: Time prior to and after the FDA mandate limiting acetaminophen to 325 mg in combination acetaminophen and opioid products. Main Outcomes and Measures: Odds of hospitalization involving acetaminophen and opioid toxicity and percentage of ALF cases from acetaminophen and opioid products prior to and after the mandate. Results: In the NIS, among 474 047 585 hospitalizations from Q1 2007 through Q4 2019, there were 39 606 hospitalizations involving acetaminophen and opioid toxicity; 66.8% of cases were among women; median age, 42.2 (IQR, 28.4-54.1). In the ALFSG, from Q1 1998 through Q3 2019, there were a total of 2631 ALF cases, of which 465 involved acetaminophen and opioid toxicity; 85.4% women; median age, 39.0 (IQR, 32.0-47.0). The predicted incidence of hospitalizations 1 day prior to the FDA announcement was 12.2 cases/100 000 hospitalizations (95% CI, 11.0-13.4); by Q4 2019, it was 4.4/100 000 hospitalizations (95% CI, 4.1-4.7) (absolute difference, 7.8/100 000 [95% CI, 6.6-9.0]; P < .001). The odds of hospitalizations with acetaminophen and opioid toxicity increased 11%/y prior to the announcement (odds ratio [OR], 1.11 [95% CI, 1.06-1.15]) and decreased 11%/y after the announcement (OR, 0.89 [95% CI, 0.88-0.90]). The predicted percentage of ALF cases involving acetaminophen and opioid toxicity 1 day prior to the FDA announcement was 27.4% (95% CI, 23.3%-31.9%); by Q3 2019, it was 5.3% (95% CI, 3.1%-8.8%) (absolute difference, 21.8% [95% CI, 15.5%-32.4%]; P < .001). The percentage of ALF cases involving acetaminophen and opioid toxicity increased 7% per year prior to the announcement (OR, 1.07 [95% CI, 1.03-1.1]; P < .001) and decreased 16% per year after the announcement (OR, 0.84 [95% CI, 0.77-0.92]; P < .001). Sensitivity analyses confirmed these findings. Conclusions and Relevance: The FDA mandate limiting acetaminophen dosage to 325 mg/tablet in prescription acetaminophen and opioid products was associated with a statistically significant decrease in the yearly rate of hospitalizations and proportion per year of ALF cases involving acetaminophen and opioid toxicity.

Determination of the Dose-Response Relationship of Epidural Dexmedetomidine Combined with Ropivacaine for Labor Analgesia.

Background: The safety and efficacy of dexmedetomidine for epidural labor analgesia have been reported in numerous literatures, but the optimal dose has not been fully determined. The objective of this study was to determine the dose-response relationship of epidural dexmedetomidine (combined with ropivacaine) for labor analgesia. Methods: A total of 120 full-term laboring parturients requesting epidural labor analgesia were enrolled in the study from July 5, 2020 to September 22, 2021. The parturients were randomly assigned to receive 0, 0.1, 0.2, 0.3, 0.4 or 0.5 µg/mL dexmedetomidine combined with 0.075% ropivacaine epidurally. An effective dose was defined as numerical rating scale (NRS) pain score ≤3 at 30-minutes of epidural drug injection. The dose-response relationship of dexmedetomidine (with ropivacaine) for epidural labor analgesia was performed using probit regression. The median effective dose (ED50) and the 95% effective dose (ED95) values for epidural dexmedetomidine combined with 0.075% ropivacaine with 95% confidence intervals (CIs) were derived by interpolation. Results: The estimated values of ED50 and ED95 with 95% CIs for epidural dexmedetomidine (combined with 0.075% ropivacaine) were 0.085 (0.015 to 0.133) µg/mL and 0.357 (0.287 to 0.493) µg/mL, respectively. No differences were found among groups for sensory block level, number of parturients with Bromage score >0, total dosage of analgesics, cesarean delivery rate, fetal birth weight, Apgar score at 1-minute, Apgar score at 5-minutes and adverse effects. Compared with other groups, group dexmedetomidine 0.5 µg/mL had a longer duration of the first stage of labor. Conclusion: The ED50 and ED95 values of dexmedetomidine for epidural labor analgesia was 0.085 and 0.357 µg/mL under the conditions of this study. Dexmedetomidine is a suitable adjuvant for epidural labor analgesia.

Analgesic comparison between perineural and intravenous dexamethasone for shoulder arthroscopy: a meta-analysis of randomized controlled trials.

INTRODUCTION: The analgesic comparison between perineural and intravenous dexamethasone on interscalene block for pain management after shoulder arthroscopy remains controversial. We conduct this meta-analysis to explore the influence of perineural versus intravenous dexamethasone on interscalene block for pain control after shoulder arthroscopy. METHODS: We have searched PubMed, Embase, Web of science, EBSCO and Cochrane library databases through April 2021 and included randomized controlled trials (RCTs) assessing the effect of perineural and intravenous dexamethasone on interscalene block in patients with shoulder arthroscopy. RESULTS: Five RCTs were included in the meta-analysis. Overall, compared with intravenous dexamethasone for shoulder arthroscopy, perineural dexamethasone led to similar block duration (SMD = 0.12; 95% CI - 0.12 to 0.35; P = 0.33), pain scores at 12 h (SMD = - 0.67; 95% CI - 1.48 to 0.15; P = 0.11), pain scores at 24 h (SMD = - 0.33; 95% CI - 0.79 to 0.14; P = 0.17), opioid consumption (SMD = 0.01; 95% CI - 0.18 to 0.19; P = 0.95) and incidence of nausea/vomiting (OR = 0.74; 95% CI 0.38-1.44; P = 0.38). CONCLUSIONS: Perineural and intravenous dexamethasone demonstrated comparable pain relief after shoulder arthroscopy.

Minimal Pilonidal Surgery vs. Common Wide Excision Operations: Better Well-Being and Comparable Recurrence Rates.

BACKGROUND: Pilonidal disease in the natal cleft is treated traditionally by a wide and deep excision of the affected area. There is growing awareness, however, to the advantages of minimally invasive surgeries. OBJECTIVES: To compare the efficacy of wide excision operations and minimal trephine surgery in patients with primary pilonidal disease. METHODS: In this retrospective study we examined surgical and inpatient records of 2039 patients who underwent surgery for primary pilonidal disease in five private hospitals between 2009 and 2012. Most procedures were of lay-open, primary midline closure, and minimal surgery types. Pilonidal recurrence rates were evaluated in a subset of 1260 patients operated by 53 surgeons each performing one type of surgery, regardless of patient characteristics or disease severity. RESULTS: With a mean follow-up of 7.2 years, 81.5%, 85%, and 88% of patients were disease-free after minimally invasive surgery, wide excision with primary closure, and lay-open surgery, respectively, with no statistically significant difference in recurrence rates. Minimal surgeries were usually performed under local anesthesia and involved lower pain levels, less need for analgesics, and shorter hospital stays than wide excision operations, which were normally performed under general anesthesia. The use of drainage, antibiotics, or methylene blue had no effect on recurrence of pilonidal disease. CONCLUSIONS: Minimally invasive surgeries have the advantage of reducing the extent of surgical injury and preserving patient's quality of life. They should be the treatment of choice for primary pilonidal disease.

Effectiveness of Ultrasound-Guided Canal Adductor Blockade for Chronic Pain and Functioning in Knee Osteoarthritis: A Prospective Longitudinal Observational Study.

METHODS: Seventy-seven patients with chronic knee osteoarthritis pain received ultrasound-guided ACB with 14 ml 0.25% levobupivacaine and 100 mcg clonidine. At baseline and 1 month after the blockade, we assessed maximal and minimal pain intensity in the knee using a numeric rating scale (NRS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). The range of motion in extension and flexion (ROMext and ROMflex) and quadriceps muscle strength of both knees (QS), Timed Up and Go Test (TUG), and 30-Second Chair Stand Test (30CST) results were determined at baseline, 1 hour, 1 week, and 1 month after the blockade. RESULTS: ACB with levobupivacaine and clonidine appeared to decrease pain severity (NRSmax 8.13 to 4.2, p < 0.001 and NRSmin 3.32 to 1.40, p < 0.001). Similarly, knee ROMext decreased from 3.90 preintervention to 2.89 postintervention at 1 month, p < 0.001; ROMflex decreased from 5.70 to 3.29, p < 0.001; TUG time decreased from 3.22 to 2.93, <0.001; QS increased from 18.43 to 22.77, p < 0.001; CST increased from 8.23 to 10.74, p < 0.001. The KOOS for pain (36.40 to 58.34), symptoms (52.55 to 64.32), activities of daily living functions (ADLs, 36.36 to 60.77), and quality of life (QoL, 17.87 to 30.97) also increased, all p < 0.001. CONCLUSION: ACB appeared to decrease pain and increase ambulation. If our preliminary results are reproducible in a planned randomized controlled trial, ACB could be a useful adjunctive pain therapy in patients with disabling pain due to knee OA.

The analgesic properties of Yu-Xue-Bi tablets in the inflammatory pain mice: By the inhibition of CCL3-mediated macrophage transmigration into the spinal cord.

ETHNOPHARMACOLOGICAL RELEVANCE: Until now, inflammatory pain, especially ones with central sensitization in the spinal cord, is far from effectively treated. Yu-Xue-Bi Tablets (YXB) is a patented medicine, which has been widely applied for inflammatory pain. However, its therapeutic characteristics and mechanism remain unknown. AIM OF THE STUDY: This study is designed to evaluate the analgesic characteristics and explore the underlying mechanism of YXB in the inflammatory pain model induced by Complete Freund's Adjuvant (CFA). MATERIALS AND METHODS: The analgesic effects were measured by Von Frey test. The expression of calcitonin gene-related peptide (CGRP) was quantified by immunofluorescence. The expression of immune factors was analyzed via Luminex assay. The further quantifications of C-C Motif chemokine ligand 3 (CCL3) were verified by Enzyme-linked immunosorbent assay (ELISA). The transmigration of macrophage and activation of microglia were evaluated by immunofluorescence. Spinal injections of purified CCL3, CCR1 antagonist (J113863) and CCR5 antagonist (Maraviroc) were used to clarify roles of CCL3 assumed in the pharmacological mechanism of YXB. RESULTS: In CFA mice, YXB ameliorated the mechanical allodynia in dose and time dependent way, suppressed the central sensitization in dose dependent way. In the L5 spinal cord, YXB downregulated the expression of macrophage M1 pro-inflammatory factors TNFRI and CCL3, inhibited the transmigration of circulating macrophage and the activation of microglia. Purified CCL3 led to the transmigration of macrophage, activation of microglia, central sensitization, and mechanical allodynia in the Sham mice. Inhibitors of CCR1 and CCR5 attenuated above symptoms in CFA mice. Purified CCL3 blocked YXB mediated down regulation of CCL3, inhibition of macrophage transmigration, but not activation of microglia. CONCLUSION: YXB exerts the analgesic effects by inhibiting CCL3-mediated peripheral macrophage transmigrate into spinal cord. This study provided a novel approach for inflammatory pain treatment and new insight into the pharmacological action of YXB.

Analgesic effects of different concentrations of ropivacaine in transversalis fascia plane block during laparotomy.

OBJECTIVE: To explore the analgesic effects of different concentrations of ropivacaine in transversalis fascia plane (TFP) block during laparotomy. METHODS: Ninety patients who underwent laparotomy admitted to our hospital from March 2019 to March 2020 were selected as the study subjects and were divided equally into a low concentration group, a medium concentration group, and a high concentration group according to the randomized grouping method. The low concentration group adopted 0.4% ropivacaine 40 ml, the medium concentration group was given 0.5% ropivacaine 40 ml, and the high concentration group was given 0.6% ropivacaine 40 ml. The hemodynamic indexes and the incidence of adverse reactions in the two groups were compared. The Numerical Rating Scale (NRS) was used to assess the postoperative pain in the three groups, the Bruggrmann comfort scale (BCS) was used to assess the comfort level in the three groups, and the Mini-mental State Examination (MMSE) was used to evaluate the postoperative cognitive function of the three groups of patients. RESULTS: The mean artery pressure (MAP) and heart rate (HR) levels at T1 and T2 were significantly lower in the medium concentration group than in the other two groups (P < 0.05). The low concentration group had a significantly higher NRS score at T2 than the medium concentration group and the high concentration group (P < 0.05). A significantly higher BCS score was observed in the high concentration group than the other two groups (P < 0.05). There were significantly higher Ramsay scores and MMSE scores in the medium concentration group than in the low concentration and high concentration groups (P < 0.05). The overall incidence of adverse reactions of the high concentration group was significantly higher than that of the low concentration group (P < 0.05), but showed similar results with the medium concentration group. CONCLUSION: The medium concentration group exhibits a better analgesic effect than the low concentration group and higher safety than the high concentration group. Therefore, the use of medium concentration ropivacaine in TFP block may provide a referential basis for clinical treatment.

Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial.

OBJECTIVE: To investigate the effects of one and two doses of intravenous dexamethasone in patients after total knee arthroplasty. DESIGN: Randomised, blinded, placebo controlled trial with follow-up at 90 days. SETTING: Five Danish hospitals, September 2018 to March 2020. PARTICIPANTS: 485 adult participants undergoing total knee arthroplasty. INTERVENTION: A computer generated randomised sequence stratified for site was used to allocate participants to one of three groups: DX1 (dexamethasone (24 mg)+placebo); DX2 (dexamethasone (24 mg)+dexamethasone (24 mg)); or placebo (placebo+placebo). The intervention was given preoperatively and after 24 hours. Participants, investigators, and outcome assessors were blinded. All participants received paracetamol, ibuprofen, and local infiltration analgesia. MAIN OUTCOME MEASURES: The primary outcome was total intravenous morphine consumption 0 to 48 hours postoperatively. Multiplicity adjusted threshold for statistical significance was P<0.017 and minimal important difference was 10 mg morphine. Secondary outcomes included postoperative pain. RESULTS: 485 participants were randomised: 161 to DX1, 162 to DX2, and 162 to placebo. Data from 472 participants (97.3%) were included in the primary outcome analysis. The median (interquartile range) morphine consumptions at 0-48 hours were: DX1 37.9 mg (20.7 to 56.7); DX2 35.0 mg (20.6 to 52.0); and placebo 43.0 mg (28.7 to 64.0). Hodges-Lehmann median differences between groups were: -2.7 mg (98.3% confidence interval -9.3 to 3.7), P=0.30 between DX1 and DX2; 7.8 mg (0.7 to 14.7), P=0.008 between DX1 and placebo; and 10.7 mg (4.0 to 17.3), P<0.001 between DX2 and placebo. Postoperative pain was reduced at 24 hours with one dose, and at 48 hours with two doses, of dexamethasone. CONCLUSION: Two doses of dexamethasone reduced morphine consumption during 48 hours after total knee arthroplasty and reduced postoperative pain. TRIAL REGISTRATION: Clinicaltrials.gov NCT03506789.

Pathogenic Mechanism of Dry Eye-Induced Chronic Ocular Pain and a Mechanism-Based Therapeutic Approach.

Purpose: Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy. Methods: We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain. Results: Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation. Conclusions: These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.

Syzygium cumini (L.) Skeels extracts; in vivo anti-nociceptive, anti-inflammatory, acute and subacute toxicity assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels has been extensively used in the ancient medical system of Pakistan, India, Bangladesh, and Sri Lanka to combat diabetes, inflammation, and renal disorders. These health-promoting aspects of S. cumini are related to bioactive metabolites such as phenolic acids, anthocyanins, tannins, and flavonoids. AIM OF THE STUDY: Earlier to this study, we have reported S. cumini extracts as potential sources of bioactive compounds bearing antioxidant and anti-inflammatory properties. However, prior further suggesting S. cumini fruit extracts for consumption against inflammatory disorders, it was mandatory to validate the claim and explore toxicity of the extracts. This study aims to determine the in vivo anti-nociceptive, anti-inflammatory, acute, and subacute toxicity properties of S. cumini crude extracts, followed by identifying and quantifying bioactive metabolites. MATERIAL AND METHODS: In the present study, the anti-nociceptive and anti-inflammatory potential of S. cumini sequential crude extracts were evaluated using formalin and glutamate-induced paw licking method in mice. The acute and sub-acute toxicity assessment of active extract was performed by oral administration in rats. An acute toxicity trial was performed with two different doses, i.e., 2000 mg/kg and 3000 mg/kg for consecutive 14 days, whereas a sub-acute toxicity study was conducted at doses of 750 mg/kg and 1500 mg/kg for the next 28 days. Identification of bioactive compounds was performed using HPLC, and at the end, in silico docking calculations of identified compounds were performed. RESULTS: The 100% methanolic extract (SCME) protected the mice from painful stimulation of formalin and glutamate in a dose-dependent manner with the maximum effect of 49% and 67% at 200 mg/kg, respectively, followed by moderate and non-influential effects of 50% methanolic extract and dichloromethane (DCM) extracts when compared to control, i.e., normal saline. The results of acute toxicity recorded LD50 of SCME over 3000 mg/kg, and no antagonistic effects were recorded during the subacute study when SCME dispensed at the rate of 750 mg/kg and 1500 mg/kg. SCME was found to induce no adverse effects to kidney, heart, liver, spleen, and paired lungs examined by hematological, serum biochemical, histological analysis. HPLC analysis of S. cumini 100% methanolic extracts revealed the presence of delphinidin 3-glucoside, peonidin-3,5-diglucoside, scopoletin, and umbelliferone at the concentration of 127.4, 2104, 31.3, 10.4 µg/g whereas in 50% methanolic extract, the quinic acid, catechin, and myricetin were present at the concentration of 54.9, 63.7, 12.3 µg/g, respectively. Umbelliferone and scopoletin are newly reported compounds in the present study. In silico docking calculations of these compounds indicated the potential of anti-nociceptive and anti-inflammatory activities. CONCLUSIONS: These findings validate that S. cumini fruit extracts are a rich source of bioactive compounds that needs to be considered to enhance biological activities with lesser side effects.

Temporal expectancy induced by the mere possession of a placebo analgesic affects placebo analgesia: preliminary findings from a randomized controlled trial.

Research on placebo analgesia usually shows that people experienced a reduction in pain after using a placebo analgesic. An emerging line of research argues that, under some circumstances, merely possessing (but not using) a placebo analgesic could induce placebo analgesia. The current study investigates how temporary expectation of pain reduction associated with different forms of possessing a placebo analgesic affects pain outcomes. Healthy participants (n = 90) were presented with a vial of olive oil (placebo), described as a blended essential oil that blocks pain sensations upon nasal inhalation, and were asked to anticipate the benefits of such analgesic oil to the self (such as anticipating the analgesic oil to reduce their pain). Participants were randomized into one of three different possession conditions: physical-possession condition (participants possessed a tangible placebo analgesic oil, inducing an expectation to acquire analgesic benefit early upon the experience of pain), psychological-possession condition (participants possessed a coupon, which can be redeemed for a placebo analgesic oil, inducing an expectation to acquire analgesic benefit later upon the experience of pain), or no-possession condition. Participants did a cold pressor test (CPT) to experience experimentally-induced pain on their non-dominant hand. Their objective physical pain responses (pain-threshold and pain-tolerance), and subjective psychological pain perception (pain intensity, severity, quality, and unpleasantness) were measured. Results revealed that participants in the physical-possession condition reported greater pain-threshold, F(2, 85) = 6.65, p = 0.002, and longer pain-tolerance, F(2, 85) = 7.19, p = 0.001 than participants in the psychological-possession and no-possession conditions. No significant group difference was found in subjective pain perception. The results of this study can advance knowledge about pain mechanisms and novel pain management.