Analgesic Effect Research Articles

Butorphanol in epidural: Could this be the breakthrough solution for safe and effective labor analgesia that we've been waiting for?

The authors have conducted a comprehensive investigation into the safety and effectiveness of butorphanol for epidural analgesia during labor. Their critical analysis of the paper and discussion of the technique's advantages and disadvantages provide a thorough understanding of the topic.

Assessment of Pelargonium graveolens flower essential oil: Antimicrobial, antioxidant, enzyme inhibition and in vivo topical analgesic and anti-inflammatory efficacy as treatment for atopic dermatitis

Background Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by pruritus and skin barrier dysfunction. This study aims to evaluate the therapeutic potential of Pelargonium graveolens (Geraniaceae) in managing AD symptoms through its essential oil. Methods The chemical composition of Pelargonium graveolens flower essential oil (PFEO) was analyzed using gas chromatography-mass spectrometry (GC-MS). Its antimicrobial, antioxidant, and anti-inflammatory properties were assessed, along with the inhibitory effects of PFEO on key enzymes involved in skin repair: tyrosinase, elastase, and collagenase. An in vivo evaluation of a gel formulation containing PFEO was also conducted to assess its anti-inflammatory and analgesic efficacy. Results GC-MS analysis identified major compounds in PFEO, including Geraniol (22.83%), beta-citronellol (19.51%), naphthalenemethanol (15.36%), and Geranyl tiglate (9.38%), with minor constituents such as linalool (3.81%) and neryl formate (1.31%). PFEO exhibited bacteriostatic activity against various bacterial and fungal strains, including Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), Bacillus anthracis, Streptococcus pyogenes, Staphylococcus epidermidis, Candida albicans, and Malassezia spp. The essential oil also demonstrated significant antioxidant properties and inhibited key enzymes linked to skin alterations in AD. Conclusions PFEO shows promising therapeutic potential for managing symptoms of atopic dermatitis due to its antimicrobial, antioxidant, and anti-inflammatory properties, as well as its analgesic effects. The findings support further exploration of PFEO as a natural alternative in the treatment of AD.

Tramadol use for chronic pain management: A thorough analysis of safety, effectiveness, and clinical recommendations

Chronic pain, especially arthritis-related pain, represents a significant medical challenge worldwide. Tramadol, a centrally acting analgesic, has emerged as a valuable treatment option for managing chronic arthritis pain. This review article provides a comprehensive analysis of tramadol’s role in chronic pain management, emphasizing its safety, effectiveness, and clinical guidelines. Literature indicates that tramadol, whether used alone or in combination therapies, effectively treats various types of arthritis-related pain, such as musculoskeletal pain, osteoarthritis, and rheumatoid arthritis. While some clinical guidelines recommend tramadol as a first-line option for persistent knee or hip osteoarthritis, others urge caution due to concerns over potential abuse and negative effects. Tramadol’s mechanism of action involves, among other things, stimulation of opioid receptors and inhibition of serotonin and norepinephrine reuptake, contributing to its analgesic effects while attempting to minimize the side effects associated with traditional opioids. However, tramadol is not without side effects, including nausea, vomiting, constipation, respiratory depression, and withdrawal symptoms if it is suddenly discontinued. Despite these challenges, tramadol remains a valuable component in managing chronic pain, especially in patients with concurrent conditions and comorbidities. Further research is necessary to determine the optimal use of tramadol and to establish its risk-benefit profile across diverse patient populations.

Genus Stachys—Phytochemistry, Traditional Medicinal Uses, and Future Perspectives

The genus Stachys represents one of the most extensive genera within the subfamily Lamioideae and ranks as one of the largest genera in the Lamiaceae family. Many Stachys species are associated with a rich history in traditional medicine across various cultures, and their extracts and essential oils are rich in non-volatile and volatile compounds. Because of their complex profile of bioactive substances, Stachys members are considered to possess an extensive spectrum of therapeutic properties, including antioxidant, anti-inflammatory, analgesic, antibacterial, cytotoxic, and wound-healing effects, as well as benefits for memory enhancement, lipid profile regulation, blood glucose control, and weight management. Despite the wide distribution and chemical diversity of the genus, studies on its biological activities remain limited. The aim of this review is to summarize the most relevant data from studies on the bioactive compounds, traditional uses, and pharmacological properties of Stachys species found in databases such as Science Direct, PubMed, and Scopus. Specific keywords were used in the search strategy, including “bioactive compounds”, “Stachys”, “Lamiaceae”, “Stachys extract”, “Stachys essential oil”, “traditional uses”, “chemical composition”, “therapeutic potential”, “clinical trials”, “in vivo studies”, “in vitro studies”. The search strategy was performed according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data from 171 studies were included. The manuscript highlights the drug-discovery potential of Stachys species, emphasizing their potential applications in medicine, cosmetics, dietary supplements, and the food industry. Moreover, it provides important data that could assist Stachys research programs.

Bilateral erector spinae plane block on opioid-sparing effect in upper abdominal surgery: study protocol for a bi-center prospective randomized controlled trial

Abstract Background Erector spinae plane block (ESPB) is a promising technique for effective analgesia. It is still uncertain if ESPB offers the same opioid-sparing effect as thoracic paravertebral block (PVB) in midline incision for upper abdominal surgery. Methods The study is a prospective, bi-center, randomized, controlled, non-inferior trial. One hundred fifty-eight patients scheduled for upper abdominal surgery will be randomly assigned to receive bilateral ESPB or PVB before surgery. The primary outcome will be the equivalent cumulative analgesia dosage of sufentanil during the surgery, which is defined as the total dosage of sufentanil from anesthesia induction to tracheal extubation. The main secondary outcomes include postoperative complications and the quality of recovery-15 score at 24 h, 48 h, and 30 days after surgery. Discussion This study will assess the opioid-sparing efficacy of ESPB and PVB, complications, and the quality of recovery of two blocks. Trial registration ChiCTR2300073030 (https://www.chictr.org.cn/). Registered on 30 June 2023.

Role of Pyrimidine Derivatives in the Treatment of Cancer

The study of the chemistry of pyrimidines is contributing to the expansion of research into the therapeutic applications of these compounds. In the field of medicinal chemistry, the sheer number of pyrimidine synthesis methods and reactions that are available opens up a world of possibilities. These investigations have been inspired by the fact that pyrimidines can be used as building blocks for a wide variety of compounds that have a physiological effect. The pyrimidine ring and its fused derivatives, which include pyrazolo[3,4-d]pyrimidine, pyrido[2,3-d]pyrimidine, quinazoline, and furo[2,3-d]pyrimidine, have garnered a great deal of attention due to the extensive variety of biological potential that they possess. In addition, fused pyrimidines are considered to be bioisosteres with purines. As a consequence of this, numerous substances, such as pyrimidine and derivatives of fused pyrimidine, have demonstrated promising anticancer potential. Pyrimidine compounds have been shown to possess a number of beneficial qualities, including antibacterial, anticancer, anti-inflammatory, antidiabetic, and analgesic effects. The purpose of this study is to shed light on the anticancer significance of certain fused pyrimidine derivatives and privileged pyrimidines through the use of various types of inhibition. Additionally, the study reveals structure-activity relationships and provides specifics regarding the synthetic compounds that were utilized in the construction of these scaffolds. The hope is that this research will assist medicinal chemists in the development of highly selective pyrimidine anticancer agents. The focus of this review article is on recent research on synthetic pyrimidine compounds that have anticancer effects. Additionally, the paper examines the chemistry and biological activities of pyrimidines.

Astaxanthin has a beneficial influence on pain-related symptoms and opioid-induced hyperalgesia in mice with diabetic neuropathy-evidence from behavioral studies

Abstract Background The treatment of painful diabetic neuropathy is still a clinical problem. The aim of this study was to determine whether astaxanthin, a substance that inhibits mitogen-activated protein kinases, activates nuclear factor erythroid 2-related factor 2 and influences N-methyl-D-aspartate receptor, affects nociceptive transmission in mice with diabetic neuropathy. Methods The studies were performed on streptozotocin-induced mouse diabetic neuropathic pain model. Single intrathecal and intraperitoneal administrations of astaxanthin at various doses were conducted in both males and females. Additionally, repeated twice-daily treatment with astaxanthin (25 mg/kg) and morphine (30 mg/kg) were performed. Hypersensitivity was evaluated with von Frey and cold plate tests. Results This behavioral study provides the first evidence that in a mouse model of diabetic neuropathy, single injections of astaxanthin similarly reduce tactile and thermal hypersensitivity in both male and female mice, regardless of the route of administration. Moreover, repeated administration of astaxanthin slightly delays the development of morphine tolerance and significantly suppresses the occurrence of opioid-induced hyperalgesia, although it does not affect blood glucose levels, body weight, or motor coordination. Surprisingly, astaxanthin administered repeatedly produces a better analgesic effect when administered alone than in combination with morphine, and its potency becomes even more pronounced over time. Conclusions These behavioral results provide a basis for further evaluation of the potential use of astaxanthin in the clinical treatment of diabetic neuropathy and suggest that the multidirectional action of this substance may have positive effects on relieving neuropathic pain in diabetes.

The analgesic effect of continuous adductor canal block combined with popliteal plexus block for total knee arthroplasty: a randomized controlled trial

The analgesic effect of continuous adductor canal block combined with popliteal plexus block for total knee arthroplasty: a randomized controlled trial

Electroacupuncture alleviates neuropathic pain in a rat model of CCD via suppressing P2X3 expression in dorsal root ganglia

Abstract Background Sciatica and low back pain are prevalent clinical types of neuropathic pain that significantly impair patients' quality of life. Conventional therapies often lack effectiveness, making these conditions challenging to treat. Electroacupuncture (EA) is an effective physiotherapy for pain relief. Prior research has demonstrated a relationship between the frequency of neuropathic pain and the analgesic impact of EA stimulation. This work aimed to assess the analgesic effects of EA in a rat model of chronic compression of the dorsal root ganglion (CCD) and to understand the underlying processes. Methods We established a rat CCD model to simulate sciatica and low back pain. EA was applied to rats with CCD at various frequencies (2 Hz, 100 Hz, and 2/100 Hz). The paw withdrawal threshold (PWT) was measured to assess analgesic effects. Additionally, protein levels of the purinergic receptor P2X3 (P2X3) and the expression of nociceptive neuronal markers were analyzed using immunohistochemistry and western blot (WB) techniques. The study also measured levels of proinflammatory cytokines TNF-α and IL-1β in the dorsal root ganglion (DRG). The involvement of P2X3 receptors was further investigated using the P2X3 agonist, α,β-methylene ATP (α,β-meATP). Results CCD rats developed pronounced mechanical allodynia. EA stimulation at all tested frequencies produced analgesic effects, with 2/100 Hz showing superior efficacy compared to 2 Hz and 100 Hz. The expression of P2X3 was increased in ipsilateral DRG of CCD model rats. P2X3 were co-labeled with isolectin B4 (IB4) and transient receptor potential vanilloid (TRPV1), indicating their role in nociception. 2/100 Hz EA treatment significantly reduced mechanical allodynia and inhibited the overexpression of P2X3, TRPV1, substance P (SP), and calcitonin gene-related peptide (CGRP) in the ipsilateral DRG of CCD model rats. Additionally, EA reduced the levels of proinflammatory cytokines TNF-α and IL-1β in the ipsilateral DRG, indicating an anti-inflammatory effect. The P2X3 agonist α,β-me ATP attenuated the analgesic effect of 2/100 Hz EA in CCD rats. The WB and immunofluorescence results consistently demonstrated P2X3 inhibition contributed to the analgesic effects of 2/100 Hz EA on CCD-induced neuropathic pain. Conclusions Our findings suggest that 2/100 Hz EA alleviates neuropathic pain in rats by inhibiting the upregulation of P2X3 receptors in the ipsilateral DRG. This study backs up EA as a viable treatment option for sciatica and low back pain in clinical settings.

Comparative Efficacy of Postoperative Pain Management Techniques Following Costal Cartilage Harvest: A Systematic Review and Network Meta-analysis

Abstract Background Efficient pain control is essential in reconstructive surgeries, particularly in procedures involving the harvest of costal cartilage. This study examines and compares different pain relief treatments using a network meta-analysis (NMA) to determine the most effective techniques for managing pain. Methods We performed a systematic review and network meta-analysis (NMA) by scanning several databases such as PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu till March 18, 2024. The review analyzed randomized controlled trials and observational studies that evaluated the effectiveness of local anesthetics and multimodal analgesia techniques in treating postoperative pain following costal cartilage harvest. Primary outcomes were pain scores at 6-, 12-, 24-, and 48-h post-surgery, while secondary outcomes included the need for rescue analgesia and opioid-related adverse effects. Results Fourteen studies involving 935 participants were included. The analysis revealed that multimodal strategies, particularly ‘Methylene Blue and Ropivacaine Intercostal Nerve Block (MB & Ropivacaine ICNB) combined with Patient-Controlled Analgesia (PCA),’ were the most effective techniques to reduce pain scores across 6, 24, and 48-h time points. “Pre-operation SAPB & PSB + PCA” was most effective in reducing pain score at 12h and significantly decreased the need for rescue analgesia and opioid-related adverse effects. In contrast, traditional ICNB with single drug consistently showed the least efficacy. Conclusion The results of our study strongly support the use of multimodal analgesic techniques instead of typical single medication ICNB for managing postoperative pain after costal cartilage harvest. These strategies not only provide superior pain control but also contribute to reducing the dependency on opioids, aligning with current clinical priorities to enhance recovery and minimize opioid-related risks. No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The effects of multimodal versus opioid-only analgesia on pain control and opioid exposure for inpatient acute pancreatitis: A retrospective cohort study

Abstract Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Acute pancreatitis (AP) is a common gastrointestinal condition that carries a significant financial and physical burden for patients due to the painful presentation and frequent need for hospitalization. Treatment varies in the type and route of analgesic used. Unmanaged pain can lead to worsening health outcomes and prolonged admissions. Further research is needed to understand current practices for managing AP. Methods This study was a retrospective, exploratory, single-center cohort study. Patients admitted to an internal medicine unit with AP from September 1, 2020, to December 31, 2021, were included. Our primary outcome was the change in pain scores during the first 24-hours after administration of the first pain-relieving medication. Secondary outcomes included change in pain scores within the first 12-hours, time to oral tolerance, characterization of analgesic orders, comparison of median pain scores by home analgesic usage, and specific inpatient opioid use. Results One hundred sixty-nine patients were screened, and 94 were included in the study. Forty-four patients were assigned to the multimodal cohort and 50 patients to the opioid-only cohort. Changes in pain scores per unit of time, assessed by a mixed-effects model, within the first 24 hours were –0.080 (SE, 0.018) in the multimodal cohort and –0.090 (SE, 0.014) in the opioid-only cohort (P = 0.780). Morphine milligram equivalents (MME) administered in the multimodal and opioid-only cohorts were 24.50 (interquartile range [IQR], 51.75) and 52.5 (IQR, 68.5) (P = 0.001), respectively. Conclusion There was no significant difference in the change in pain scores between patients receiving multimodal therapy and those receiving opioids only. Significantly fewer MME were administered in the multimodal group, suggesting that multimodal therapy can be opioid-sparing in AP.

Network Pharmacology and Molecular Dynamics Simulations Reveal the Mechanism of Total Alkaloid Components in Anisodus Tanguticus (Maxim.) Pascher in Treating Inflammation and Pain.

This study aimed to elucidate the mechanism that total alkaloids in Anisodus tanguticus (AT)(Maxim.) Pascher played anti-inflammatory and analgesic effects. In this paper, the anti-inflammatory effect in the total alkaloids of AT was confirmed via lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 cells and the main components of AT were immediately analyzed by UPLC/MS. Disease targets were obtained in GeneCards and DisGeNET. Targets of major compounds were searched in ETCM, TCMSP and other databases. The protein-protein interaction (PPI) network was constructed using STRING database, and Cytoscape was used for core targets screening. GO and KEGG enrichment analysis were performed using Daivid database. Sailvina was used for molecular docking. Molecular dynamics simulation analysis was performed using the Amber 20 program. The results showed that the main components in AT were anisodamine, atropine, fabiatrin, scopolamine, scopoletin and scopolin, possibly exerting anti-inflammatory and analgesic effects through pathways such as EGFR tyrosine kinase inhibitor resistance and IL-17 signaling pathway. Fabiatrin and scopolin could be potential drugs with good anti-inflammatory and analgesic effects.

Increasing the Use of Newborn Pain Treatment Following the Implementation of a Parent-Targeted Video: An Outcome Evaluation

Background/Objectives: Despite strong evidence that breastfeeding, skin-to-skin care, and sucrose reduce pain in newborns during minor painful procedures, these interventions remain underutilized in practice. To address this knowledge-to-practice gap, we produced a five-minute parent-targeted video demonstrating the analgesic effects of these strategies and examined whether the use of newborn pain treatment increased in maternal–newborn care settings following the introduction of the video by nurses. Methods: The design was a pre–post outcome evaluation. The participants were infants born in eight maternal–newborn hospital units in Ontario, Canada. Data on newborn pain treatment were obtained from a provincial birth registry. Descriptive statistics and chi square tests were used to compare the before-and-after changes in the use of pain treatment. Results: Data on 15,524 infants were included. Overall, there was an increase in the proportion of newborns receiving any pain treatment comparing before (49%) and after (54%) the video intervention (p < 0.0001) and a decrease in the proportion of newborns receiving no pain treatment pre- (17.6%) and post-intervention (11.5%) (p < 0.0001). Most of the change aligned with increased sucrose use (35% to 47%, p < 0.0001) in three of the larger units. Nevertheless, considerable increases in the use of breastfeeding and/or skin-to-skin care (24% to 38%, p < 0.0001) were also observed in three of the smaller units. Conclusions: The video intervention was effective at increasing the use of pain treatment for newborns. Though the overall increases were modest, there were some large increases for specific methods of pain treatment in certain maternal–newborn units, reflecting the diversity in practice and context across different sites.

Antiedematogenic and anti-inflammatory effects of the essential oil from the fruits of Piper tuberculatum Jacq. (Piperaceae) in animal models.

Piper tuberculatum, traditionally known as 'pimenta-d'arda,' 'pimenta-longa,' or 'pimenta de macaco,' has been used in Brazilian folk medicine to treat inflammatory symptoms, It is used for its sedative effects in pain relief.Considering this species' significant essential oil content, the present study aimed to evaluate the anti-edematogenic and anti-inflammatory effects of the essential oil Piper tuberculatum (EOPT) in vivo. To this end, Swiss mice (Mus musculus) of both sexes were treated orally with the EOPT at 50, 100, and 250 mg/Kg. The rotarod and open field evaluated the potential activity in the central nervous system. At the same time, formalin and abdominal writhing tests were carried out to perform the pharmacological screening of the essential oil. Next, the anti-edematogenic effect was assessed using paw edema models induced by carrageenan, dextran, histamine, and arachidonic acid. The anti-inflammatory activity was then characterized in peritonitis (acute) and granuloma (chronic) models. All the EOPT doses (50, 100, and 250 mg/kg) had analgesic effects associated with anti-inflammatory mechanisms in screening models. Accordingly, the treatment (EOPT 100 mg/Kg) inhibited the inflammatory process in acute and chronic models. In conclusion, EOPT has analgesic, antiedematogenic, and anti-inflammatory effects, highlighting its potential use in developing anti-inflammatory drugs.

Ultrasound-guided anterior iliopsoas muscle space block compared with fascia iliaca compartment block in elderly hip surgery: A randomized controlled trial

Background: Elderly hip fracture patients experience severe pain. Surgical stress and pain during position changes for spinal anesthesia puncture can adversely affect hemodynamics. The objective of this study was to compare the perioperative analgesic efficacy of anterior iliopsoas muscle space block with supra-inguinal fascia iliaca compartment block (S-FICB) in elderly patients undergoing hip surgery. Method: In this randomized control trial, 66 patients were randomly assigned to either the iliopsoas space or the S-FICB group. Each patient received 30 mL of ropivacaine 0.375%. Perioperative pain scores were assessed and compared in both groups. The primary outcome was pain scores during changes in position for neuraxial anesthesia. Secondary outcomes included postoperative pain intensity, inflammatory markers for 12 to 24 hours, and perioperative adverse reactions. Results: The iliopsoas space group demonstrated a faster median block onset of 7 [6–8] minutes compared to S-FICB 14.50 [13–16] minutes (P < .001). Neuraxial anesthesia position changes resulted in lower pain scores for iliopsoas 2 [1–2] versus S-FICB 3 [3–4] (P < .001). Resting pain scores were similar at 12 hours post-surgery, but during exercise, the iliopsoas group had significantly lower scores [1–2] compared to S-FICB 4 [2–4] (P < .001). After 24 hours, C-RP levels were lower in the iliopsoas group (14.86 ± 1.23 mg/L) than S-FICB (17.90 ± 1.25 mg/L) (P < .001). The 2 groups differed from one another (P < .001). These findings suggest that iliopsoas space block may offer faster, superior dynamic pain control, and potentially reduced inflammation compared to FICB block for postoperative pain management. Conclusion: In elderly hip fracture patients, the anterior iliopsoas space block works slightly better than S-FICB at providing effective perioperative analgesia.

Relative analgesic effectiveness of pharmacological interventions in knee osteoarthritis: a component network meta-analysis

Abstract Introduction Knee osteoarthritis (KNOA) is a chronic, burdensome, highly prevalent degenerative disease1. As there is no current cure for KNOA, treatments are primarily focused on pain management. While pharmacological interventions typically demonstrate superiority to placebo for pain relief, evidence regarding their relative effectiveness is lacking. Component Network Meta-Analysis (CNMA) is a relatively new technique that uses all available evidence to estimate effects of each treatment against all other treatments via its performance relative to a common comparator such as placebo. Aim To evaluate relative analgesic effectiveness of pharmacotherapies for KNOA using CNMA to provide comprehensive, evidence-based information for clinical decisions and inform future guidelines. Methods We performed a comprehensive search of major electronic databases (MEDLINE, EMBASE and CENTRAL) and trial registries from inception to January 2021 without language restriction for RCTs that compared treatment for adults with KNOA with another treatment or control listed in NICE guidelines: paracetamol, NSAIDs (with and without gastroprotection), COX2-inhibitors, opioids, duloxetine, capsaicin, hyaluronic acid (HA) and corticosteroids (CS), administered via oral, topical, transdermal or intra-articular (IA) routes2. Assessment at the following time windows: immediate (up to two weeks), short (closest to 3 months), medium (closest to 6 months) and long (closest to 12 months). A random-effects CNMA was used to estimate relative treatment effects; mean differences (MD) for a primary outcome of pain (0-10) within a frequentist framework3. Certainty of evidence was evaluated using the Confidence in Network Meta-Analysis (CINeMA) with risk of bias (RoB) assessed using the revised Cochrane RoB2 tool. This study does not require ethical approval as it is a systematic review and CNMA of already approved trials and is registered with PROSPERO, CRD42020184192. Results Screening initially identified 33298 citations, reduced to 202 studies after a full-text review. In the immediate-term relative effectiveness ranged between -1.41 (95% confidence interval [CI] -2.23, -0.60) for transdermal NSAIDs and -0.25 (-0.48, -0.02) for IAHA. In the short term, we found evidence of significant effects for all interventions except topical capsaicin and transdermal opioids; effects ranged from -2.09 (-3.69, -0.49) for transdermal NSAIDs to -0.31 (-0.57, -0.04) for IACS. In the medium term, we only found a significant effect for IAHA with MD -0.36 (-0.62, -0.10). We did not find evidence of a significant effect in the long term. 137 (67.8%) of 202 studies included were rated at high risk of bias, 50 (24.7%) at some concerns, and 15 (7.5%) at low, and the certainty of evidence ranged from moderate to very low. Discussion/Conclusion This large-scale and first CNMA provides comprehensive evidence for KNOA pain management. We found evidence of significant effects for several single and multicomponent interventions for immediate and short-term effectiveness. However, their effect diminished over time. While we employed ranking metrics, we could not declare a clear winner among competing interventions due to the between-study heterogeneity, strength of evidence, and the complex nature of KNOA pain. Findings from this study should serve as a tool to inform future guideline developments and clinical decisions, emphasising a holistic approach towards managing KNOA pain with considerations to routes of administration, comorbidities, polypharmacy, and patient needs.

Comparative Study to Evaluate the Efficacy of Dexmedetomidine and Magnesium Sulfate as Adjuvants to 0.5% of Hyperbaric Bupivacaine in Patient Undergoing Abdominal Hysterectomy by Spinal Anesthesia: A Randomized, Double-blind Study

Abstract Objective: Abdominal hysterectomy is a common gynecological procedure. While spinal anesthesia offers pain relief, its short analgesic effect is limiting. In this context, there are not many research that examined magnesium sulfate, dexmedetomidine, and 0.5% hyperbaric bupivacaine. Our research addresses this gap as “Comparing Dexmedetomidine and Magnesium Sulfate as Adjuvants to Hyperbaric Bupivacaine for Abdominal Hysterectomy”. Methods: Ninety patients with the American Society of Anesthesiologists Classification I and II, aged 30–60, planned for abdominal hysterectomy were randomized to either dexmedetomidine or magnesium sulfate or control group as adjuvants to hyperbaric bupivacaine. The primary objective was to find the effectiveness of the anesthesia in terms of both sensory and motor blocks (onset, duration, and severity), with the secondary objective was to find out any other associated complications. Results: In comparison to the magnesium sulfate group, the dexmedetomidine group’s anesthetic effect began significantly more immediately and persisted much longer (P < 0.001). The groups did not vary statistically significant in terms of side effects or hemodynamic instability. Conclusion: Adjuvants such as dexmedetomidine or magnesium sulfate along with hyperbaric bupivacaine, for abdominal hysterectomy under spinal anesthesia, provide effective anesthesia. Dexmedetomidine (10 μg) and magnesium sulfate (100 mg) both showed safe intrathecal adjuvant usage. Remarkably, dexmedetomidine surpasses magnesium sulfate by swiftly inducing sensory and motor blocks, extending their duration, and enhancing analgesia. Notably, both adjuncts yield no adverse effects. Overall, these findings underscore the potential of dexmedetomidine as a more effective adjuvant in spinal anesthesia protocols for abdominal hysterectomy procedures.

Analgesic Effect of Conventional Paravertebral versus Mid transverse Process to Pleura Blocks on Post Mastectomy Pain in Unilateral Modified Radical Mastectomy Surgeries

Analgesic Effect of Conventional Paravertebral versus Mid transverse Process to Pleura Blocks on Post Mastectomy Pain in Unilateral Modified Radical Mastectomy Surgeries

Impact of remimazolam on postoperative inflammatory markers and complications in thoracoscopic pulmonary lobectomy patients: A retrospective analysis

Remazolam is widely used for procedural sedation in intensive care units. It has been shown to have anti-inflammatory and organ-protecting properties. However, the changes in inflammatory markers and analgesic effects of remazolam after thoracoscopic pulmonary lobectomy remain unclear. This study aims to assess the effects of the novel drug remimazolam on inflammatory factor levels and postoperative complications in thoracoscopic pulmonary lobectomy patients, providing a scientific basis for clinical use. This retrospective study analyzed 200 thoracoscopic pulmonary lobectomy patients, who were divided into a control group and a remimazolam group based on their anesthesia method. Patients in ramazolam group were anesthetized with ramazolam, while patients in control group were anesthetized with propofol. All patients were performed by the same physician team and anesthesia team. Inflammatory factors (including interleukin-6 [IL-6], C-reactive protein [CRP], including interleukin-8) were measured preoperatively and postoperatively, and postoperative complication rates were compared between the 2 groups. The levels of IL-6 and CRP were significantly higher in the remimazolam group at 7 days postoperatively compared to the control group. No significant differences were observed in preoperative inflammatory factors or postoperative including interleukin-8 levels between the 2 groups. Additionally, there were no significant differences in the overall incidence of postoperative complications or in specific complications such as pulmonary infection, atelectasis, subcutaneous emphysema, pneumothorax, surgical site infection, and arrhythmia. Patients receiving remimazolam had higher postoperative IL-6 and CRP levels compared to the control group, without an increase in postoperative complications. In clinical use, attention should be paid to the control of inflammatory indicators in patients using remazolam. However, due to potential confounding factors and the retrospective design, we cannot establish a causal relationship between remimazolam and elevated inflammatory markers. These findings suggest a possible association that requires cautious interpretation. Further research is needed to assess the clinical relevance and explore the underlying mechanisms.

Semaglutide Ameliorates Diabetic Neuropathic Pain by Inhibiting Neuroinflammation in the Spinal Cord

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats. Methods: Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated. Results: SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group. Conclusions: These results indicate SEMA’s neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects.