Search Results (3,674)

Nitrous oxide (N₂O), commonly known as laughing gas, is widely used for its anesthetic and analgesic properties in medical settings. However, its recreational abuse has escalated, leading to severe neurological complications including cognitive impairment, yet the underlying mechanisms remain poorly understood. In this study, male C57BL/6 J mice were exposed to either normal air inhalation or nitrous oxide inhalation for 28 days to evaluate the effects of repeated nitrous oxide exposure on cognitive function. We employed hippocampal transcriptome sequencing, real-time PCR, Western blotting, and non-targeted plasma metabolomics to explore potential regulatory mechanisms. Repeated nitrous oxide exposure impaired motor skills, learning, and cognitive abilities in mice. Integrative multi-omics analysis revealed that differentially expressed metabolites and genes synergistically disrupted energy metabolism through co-regulation of the TCA cycle, MAPK signaling pathway, and pyrimidine metabolism, ultimately leading to impaired cellular signaling, nucleic acid synthesis, and cognitive dysfunction. Our study provides novel multi-omics insights into the MAPK/ERK/CREB-mediated neurotoxicity and energy metabolism collapse induced by nitrous oxide as a recreational drug of abuse, offering new directions for clinical intervention. Full article

Background/Objectives: Heracleum millefolium Diels (HMD) is a traditional Tibetan medicinal herb that has been reported to possess analgesic, anti-edematous, and anti-inflammatory activities. However, its chemical composition and anti-inflammatory mechanisms remain unclear. Methods: In this study, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS), combined with database searching and “seed”-based molecular networking, was used to systematically characterize the chemical constituents of HMD. Furthermore, an integrated strategy combining network pharmacology, molecular docking, and cellular validation was applied to explore potential anti-inflammatory mechanisms associated with HMD. Results: A total of 472 compounds were identified or tentatively identified from HMD. Network pharmacology analysis predicted five key targets, namely TNF, IL-6, IL-1β, GAPDH, and AKT1, together with four potential bioactive constituents, including velutin, artemitin, kaempferol, and naringenin. Pathway enrichment analysis indicated that the potential anti-inflammatory effects of HMD were mainly associated with lipid and atherosclerosis and the AGE-RAGE signaling pathway. Molecular docking suggested potential favorable interactions between the selected constituents and key targets. Moreover, cellular experiments demonstrated that the four compounds significantly inhibited inflammatory responses in LPS-stimulated RAW264.7 macrophages. Conclusions: This study systematically characterized the chemical profile of HMD and preliminarily explored its potential anti-inflammatory mechanisms, providing a scientific basis for further investigation of its bioactive constituents and pharmacological properties. Full article

Perioperative neurocognitive disorders (PND) encompass a spectrum of cognitive impairments occurring across the surgical period and are associated with significant morbidity, delayed recovery, and reduced quality of life. Although established risk factors include advanced age, cardiovascular disease, and preexisting cognitive impairment, the contribution of mood disorders to PND susceptibility remains incompletely understood. This review systematically examines the neurobiological overlap between mood disorders, particularly major depressive disorder (MDD) and bipolar disorder, and PND, with emphasis on shared biomolecular mechanisms. We identify convergent pathophysiologic pathways including hypothalamic–pituitary–adrenal (HPA) axis dysregulation, chronic neuroinflammation, NF-κB-mediated cytokine signaling, microglial priming, tryptophan–kynurenine pathway dysregulation, and brain-derived neurotrophic factor (BDNF) suppression. These mechanisms collectively suggest that patients with preexisting mood disorders may enter surgery in a biologically sensitized neuroimmune state, lowering the threshold for exaggerated neuroinflammatory responses and postoperative cognitive dysfunction. Recognition of mood disorders as modifiable perioperative vulnerability states may inform preoperative risk stratification, guide anesthetic and analgesic management, and support the development of targeted interventions to reduce postoperative cognitive complications and improve surgical outcomes. Full article

Solanum elaeagnifolium has been utilized for its analgesic, anti-inflammatory, and antioxidant properties to treat a range of conditions, including pain and inflammation. It possesses antibacterial, insecticidal, and molluscicidal properties as well. To investigate the pharmacological potential of the S. elaeagnifolium extract, in vitro, in vivo, and in silico studies were used. Albumin denaturation, heat-induced anti-haemolytic action, and lipooxygenase inhibition were the three techniques used to test anti-inflammatory effectiveness. The phenolic chemicals utilized were identified through the use of high-performance liquid chromatography (HPLC). The effectiveness of the extract in lowering problems connected to diabetes was further evaluated by evaluating fructosamines, carbonyl groups, and β-amyloid formations in albumin glycation. Regarding in vivo studies, the Writhing test and the tail flick test were the two techniques used to evaluate analgesic activity. For docking analysis, we used the following identifiers: cyclooxygenase (PDB ID: 6COX), lipooxygenase (PDB ID: 3V99) and VC1 domain of the receptor for advanced glycation products (PDB ID: 7LMW). The most prevalent phenolic chemicals, according to HPLC analysis, were 3,4-dihydroxybenzoic acid (4.78%), caffeic acid (1.28%), gallic acid (8.18%), ursolic acid (2.6%), syringic acid (1.78%), quercetin (24.09%), catechin (6.67%), and p-coumaric acid (20.49%). Significant suppression of albumin glycation and fructosamine production was demonstrated by the extract, indicating that it may help lessen difficulties associated with diabetes. Furthermore, the extract demonstrated a strong anti-inflammatory impact, with an IC₅₀ of 146 ± 1.17 μg/mL for lipooxygenase inhibition, 87.64 ± 5.35 μg/mL for anti-haemolytic action, and 86.94 ± 1.63 μg/mL for albumin denaturation inhibition. A similar analgesic effect to those of analgesic medications was also demonstrated by SEFE extract. Reinforcing the relevance of the observed effects, the in silico study of the tested activities validated these findings. These findings indicate significant pharmacological promise in the management of diabetes consequences, including inflammation and protein glycation, as well as an analgesic. Full article

Background/Objectives: Medication safety is a critical concern in older adults due to age-related vulnerability, multimorbidity, and polypharmacy. Pro Re Nata (PRN, “as needed”) prescribing is common in geriatric care but may be interpreted inconsistently across healthcare professionals, potentially increasing the risk of medication errors. This study aimed to evaluate PRN prescribing patterns in hospitalized older adults and assess interprofessional perceptions of the clarity and appropriateness of PRN prescribing for conditions. Methods: We conducted a prospective, single-day observational study in a French geriatric university hospital, including all patients aged ≥65 years with at least one medication prescription. PRN prescriptions were extracted from electronic medical records and independently assessed by a pharmacist, nurse, and physician for clarity and appropriateness. Descriptive statistics summarized PRN use, chi-square tests assessed interprofessional differences, and multivariate logistic regression identified predictors of appropriate PRN wording. Results: Among 316 patients, 1035 PRN prescriptions were analyzed, representing 24.5% of all medication entries. Only 51.3% (n = 531) were deemed appropriate by all evaluators. Significant differences in interpretation were observed across professional groups (p < 0.001 for most pairwise comparisons). PRN prescriptions were most frequent in long-term care units and primarily involved gastrointestinal agents, analgesics, and psychotropic medications. Multivariate analysis showed that hospitalization in long-term care (OR = 4.17; 95% CI 2.48–7.03) or rehabilitation units (OR = 2.07; 95% CI 1.22–3.53) with a higher number of prescriptions administered under a therapeutic protocol PRN (OR = 2.27; 95% CI 1.39–3.63) were independently associated with appropriate wording, while a higher total number of PRN prescriptions reduced appropriateness (OR = 0.87; 95% CI 0.82–0.94). Conclusions: PRN prescribing is frequent in hospitalized older adults and often involves high-risk or potentially inappropriate medications. Substantial interprofessional variability in the interpretation of PRN medication wording requires appropriate, standardized, and clinical PRN guidelines to improve medication safety and reduce potential adverse events in geriatric practice. Full article

Concurrent exposure to analgesic and psychotropic drugs is frequent in patients with pain, psychiatric comorbidity, frailty, or acute-care needs. The clinically important question is whether analgesics and psychotropic drugs act on the same metabolic, transporter, receptor, ion-channel, or cellular stress systems. This narrative mechanistic review discusses those points of contact. CYP-mediated inhibition or induction, phenoconversion, altered parent-to-metabolite ratios, and blood–brain barrier transporter effects can change both systemic and central exposure, particularly through CYP2D6, CYP3A4, CYP2C9, CYP2B6, and P-glycoprotein. Pharmacodynamic toxicity may involve serotonergic excess, opioid and GABAergic effects in respiratory-control networks, hERG/IKr-related loss of repolarization reserve, or dopamine D2 receptor blockade. Non-opioid analgesics and psychotropic background therapy add further pathways involving renal and gastrointestinal vulnerability, hematological toxicity, mitochondrial injury, and altered central nervous system function. At the cellular level, mitochondrial dysfunction, oxidative stress, calcium dysregulation, and endoplasmic reticulum stress are discussed primarily as mechanistic or preclinical contributors unless direct clinical evidence is available. Overall, analgesic–psychotropic co-exposure is presented as a clinically important example of pathway convergence, while pharmacogenomic and computational approaches are interpreted in relation to drug exposure, organ reserve, and patient-specific vulnerability. Full article

Background: Achilles tendon contracture is a prevalent issue in pediatric populations, often leading to complications such as toe walking and limited ankle dorsiflexion. This study aims to compare the clinical outcomes of two surgical techniques for Achilles tendon lengthening—conventional percutaneous lengthening and Z-plasty—in children with idiopathic Achilles tendon contracture, while assessing the adequacy of a six-week postoperative immobilization period. Methods: A retrospective analysis was conducted on 60 pediatric patients (ages 5–17) who underwent Achilles tendon lengthening at our institution between 2021 and 2025. Patients were divided into two groups: 25 receiving percutaneous lengthening and 35 undergoing Z-plasty. Inclusion criteria encompassed idiopathic contracture with a follow-up of over 12 months. Outcomes measured included ankle dorsiflexion, time to resume normal activities, length of hospital stay, duration of cast immobilization, complications, the likelihood of choosing the same treatment method again, taking analgesics, AOFAS score, and patient/guardian satisfaction. Results: Both surgical methods resulted in significant improvements in ankle dorsiflexion and functional outcomes. The percutaneous group demonstrated a mean increase of 30° in dorsiflexion, while the Z-plasty group showed a mean increase of 32.5°. The time from surgery to resuming normal activities in the Z-plasty group ranged from 6 to 11 weeks, which was significantly higher than the range of 6 to 7 weeks in the percutaneous lengthening group, p = 0.024. Guardian and patient satisfaction was high in both groups, with 94.3% of patients from the Z-plasty group and 100% of patients from the percutaneous group expressing willingness to choose the same treatment again. Four patients (11.4%) from the Z-plasty group and one patient (4%) from the percutaneous lengthening group developed complications. Conclusions: The period of cast immobilization of six weeks helped achieve good outcomes and caused few complications in children from both study groups. The conventional percutaneous approach to Achilles tendon lengthening in children helps achieve substantial correction of ankle dorsiflexion with a low risk of complications. Due to the risk of selection bias, the results should be interpreted with caution. Full article

Background/Objectives: The clinical management of visceral pain remains a significant challenge. Our previous study confirmed the analgesic efficacy of dexmedetomidine (Dex) in a mouse model of inflammatory visceral pain (IVP). However, the underlying molecular mechanism, particularly regarding immune regulation, has not been fully elucidated. Methods: In the present study, transcriptomic profiling of both physiological and disease states was performed to characterize associated molecular and immune signatures. Key driver genes were identified by integrating differentially expressed genes (DEGs) from the IVP model with potential Dex targets derived from network pharmacology. Molecular docking simulations evaluated binding interactions. The correlations between Dex’s targets and immune cell infiltration patterns, with a focus on macrophages, were analyzed. Results: Multi-tissue analysis revealed a strong association between IVP pathogenesis and pro-inflammatory immune responses, specifically a shift in macrophage polarization. Within this dysregulated network, seven proteins were identified as direct potential targets of Dex. Among these, six core targets, such as ADGRF1, IDO1, JAK3 and NR1H4, demonstrated the most significant correlations with M1-like macrophages and exhibited strong in silico binding potential with Dex. Conclusions: This integrated analysis suggests that Dex may alleviate visceral pain by modulating a specific gene network linked to pro-inflammatory macrophage activation, thereby promoting the restoration of immune balance. Our findings provide a novel mechanism-informed perspective for the application of Dex in visceral pain therapy. Full article

Background/Objectives: The objective of this study was to evaluate age-specific effects of intraoperative platelet-rich plasma (PRP) administration on postoperative pain, wound healing, and bleeding after tonsillectomy. Methods: PubMed, Embase, Scopus, Google Scholar, and Cochrane databases were searched from inception to October 2025. Randomized controlled trials comparing intraoperative PRP with placebo or no treatment in patients undergoing tonsillectomy were included. Data on postoperative pain, wound healing, and bleeding were extracted and analyzed using standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses were performed by age (adults versus children) and by postoperative day. Results: Nine randomized controlled trials comprising 442 participants were included. In adults, PRP significantly reduced postoperative pain (SMD = −1.26 [−1.70 to −0.81]) and improved wound healing (SMD = −1.43 [−2.65 to −0.22]). The analgesic effect was greatest during the early recovery period (postoperative days 0–5) and diminished thereafter. There were no significant differences in primary postoperative bleeding (OR = 0.49 [0.04 to 5.61]) or secondary postoperative bleeding (OR = 0.23 [0.02 to 2.16]) between the PRP and control groups. In children, PRP did not significantly affect pain or bleeding outcomes. Conclusions: Intraoperative PRP may reduce early postoperative pain and may promote mucosal recovery in adults. However, its clinical efficacy in children remains unclear. Further well-designed, age-stratified trials are warranted to clarify the role of PRP in enhancing postoperative recovery. Full article

Neuropathic pain is a chronic condition frequently associated with peripheral nerve injury and is characterized by significant structural and molecular alterations. Photobiomodulation therapy (PBMT) has demonstrated analgesic and anti-inflammatory effects; however, its influence on neurotrophic and myelin-associated repair mechanisms remains incompletely understood. The aim of this study was to investigate the effects of PBMT on ultrastructural, morphometric, and molecular changes induced by chronic constriction injury (CCI) of the sciatic nerve in male rats, with an emphasis on NGF and P0 expression. Neuropathy was induced using the CCI model of the sciatic nerve. PBMT was initiated 14 days after injury and administered in ten sessions using an infrared 904 nm laser. Transmission electron microscopy, morphometric analysis, immunofluorescence, and Western blot analyses were performed to evaluate neural regeneration and the expression of NGF and P0. Animals subjected to CCI exhibited ultrastructural changes consistent with Wallerian degeneration, accompanied by reduced NGF and P0 expression in the sciatic nerve. In contrast, PBMT markedly preserved nerve morphology, restored NGF expression, and significantly increased P0 protein levels. Together, these findings demonstrate that PBMT enhances peripheral nerve repair by promoting both molecular and structural mechanisms involved in axonal regeneration and myelin restoration. Restoration of NGF expression and increased P0 protein expression suggest that these mechanisms contribute to the regenerative effects of PBMT, supporting its potential as a safe, noninvasive therapeutic strategy for peripheral neuropathies. Full article

Background: Temporomandibular disorders (TMD) are associated with musculoskeletal pain affecting the masticatory muscles and temporomandibular joint (TMJ). Low-level laser therapy (LLLT) is a therapeutic modality with analgesic, anti-inflammatory, and biostimulatory effects. Protocol and laser parameter settings for TMD management have not yet been established. The aim of this prospective study was to evaluate the effectiveness of low-level laser therapy in reducing pain in TMD patients. Methods: Sixty-three participants treated at the Department of Prosthodontics, School of Dental Medicine, University of Belgrade, were sorted to the LLLT group and the control splint-medication group (SMG), which received occlusal splint therapy, with nonsteroidal anti-inflammatory drug treatment (NSAID; Ibuprofen). Results: Both therapeutic approaches resulted in significant pain reduction and improvement in patients’ quality of life. No statistically significant differences were observed between the groups, LLLT patients demonstrated a higher rate of successful treatment outcomes, reduction in pain intensity during the treatment. Conclusion: The applied LLLT was associated with significant reduction in pain intensity and improvement in oral health-related quality of life in patients with TMD. Although no statistically significant differences between the groups were demonstrated at the individual post-treatment assessment points, these findings support LLLT as a potentially useful non-invasive conservative treatment option. Full article

Parturition is associated with pain in all mammals, yet our understanding of this physiological process differs considerably between women and animals. In women, parturition pain has been extensively investigated, whereas in domestic animals it remains poorly characterized, despite its potential implications for maternal welfare and neonatal outcomes. This systematic review aimed to evaluate evidence on physiological pain during natural parturition in domestic animals and to compare it with that reported in women using observer-based assessment methods. PubMed, Scopus, Embase, and Web of Science were searched from inception to 31 March 2026. Eligible studies assessed parturition pain using behavioural, physiological, or biochemical indicators. Twenty-nine studies met the inclusion criteria (18 animal, 11 human studies). In domestic animals, most investigations focused on behavioural and endocrine responses associated with dystocia or postpartum discomfort rather than on the intensity of intrapartum pain itself. The strongest evidence of severe pain during the expulsive phase was reported in goats and sows. In women, observer-based assessment methods were limited and heterogeneous. In conclusion, the available evidence is consistent with a nociceptive component of labour across species; however, it remains insufficient to quantify physiological parturition pain in most domestic animals or justify routine analgesic treatment solely on welfare grounds. The development and validation of species-specific multidimensional tools for parturition pain assessment should therefore be considered a research priority. Full article

Background: This systematic review aimed to evaluate the safety and outcomes of extraperitoneal cesarean section (EPCS), including the French Ambulatory Cesarean Section (FAUCS), by comparing them to those of transperitoneal cesarean section (TCS). Data Sources: The search was conducted using the following electronic bibliographic databases: PubMed, Web of Science, and Scopus. Studies were included if they were observational or interventional and investigated EPCS, including FAUCS, as the primary intervention. Exclusion criteria were animal studies, reviews, editorials, and conference abstracts. Methods: Two reviewers independently assessed the risk of bias using RoB 2 for RCTs and ROBINS-I for retrospective studies. Studies were grouped into comparable categories, and data were synthesized in summary tables and by comparative descriptive analysis. Results: In comparative studies, EPCS was associated with significantly lower rates of postoperative complications, such as fever (4% vs. 16% for TCS) and elevated C-reactive protein or leukocytosis (0% vs. 16–20%). EPCS reduced postoperative pain, with lower VAS scores at 24 h (e.g., 2.5 vs. 4.0 in TCS, p < 0.001) and shorter analgesic use. Time to return of bowel function was faster in EPCS and modified EPCS (6–8 h vs. 18–24 h in TCS, p < 0.01). Hospital stays were shorter after EPCS (4.15 ± 0.89 days vs. 4.82 ± 1.34 days, p = 0.027). FAUCS enabled early discharge within 24–48 h in 86–93% of cases and reduced morphine use (0.8% vs. 38% in TCS). Neonatal outcomes, including Apgar scores and cord pH, were similar across all groups. Conclusions: EPCS offers several potential advantages over TCS, including less postoperative pain, faster recovery, and shorter hospital stays. EPCS and its FAUCS variant are also associated with quicker return of bowel function and lower analgesic needs. TCS, while enabling faster fetal delivery, is linked to greater postoperative discomfort and slower recovery. However, current evidence is limited, and further high-quality trials are needed to confirm these benefits and assess long-term outcomes. Full article

Mitragyna speciosa Korth. (Kratom) is a plant native to Southeast Asia, traditionally used for its stimulant and analgesic properties. Beyond mitragynine, the principal alkaloid dominating M. speciosa research, this study explored the cosmeceutical and nutraceutical potential of its phenolic and flavonoid constituents. Kratom leaf extract (MLE) was obtained via ultrasound-assisted extraction optimized by Central Composite Design, yielding high polyphenol content and antioxidant capacity. The optimized MLE showed measurable collagenase inhibition (IC₅₀ = 92.63 ± 7.81 µg/mL) while maintaining fibroblast viability (>80%). UHPLC-ESI-QTOF-MS/MS tentatively identified chlorogenic acid, rutin, and kaempferol 3-glucosyl-(1→6)-galactoside (K3G). Chlorogenic acid and rutin were quantified by HPLC at 31.37 ± 2.41 and 18.76 ± 1.66 µg/mg extract, respectively, while K3G remained linked to an unidentified peak. Mitragynine was also quantified at an appreciable level (59.38 ± 0.21 µg/mg extract), indicating that removal of the alkaloid fraction is required before application. Molecular docking identified chlorogenic acid as the strongest predicted collagenase binder (−12.82 kcal/mol), though chlorogenic acid and rutin together could not fully account for the extract’s activity, suggesting possible contributions from K3G and other unidentified compounds. These findings provide preliminary evidence for the cosmeceutical potential of kratom leaf extract, pending control of its alkaloid content. Full article

Background/Objectives: Self-medication and keeping medicine inventory in households are common practices, even among healthcare professionals and healthcare professions students. Despite their knowledge of appropriate medicine use and storage, these practices are not always responsible and may pose health risks. This study aimed to describe self-medication practices, contents of home pharmacies, and habits of keeping medicine inventories in households of medical and pharmacy students at the Faculty of Medicine, University of Rijeka. Methods: In this cross-sectional study conducted in 2025, 60 third-year medical and pharmacy students interviewed members of their households regarding contents of home pharmacies and self-medication practices and compiled inventories of medicines kept at home. Results: Of the participating students, 70.0% were female. Healthcare professionals (physicians or pharmacists) were present in 23.3% of households. Medicines were stored in a designated location (“home pharmacy”) in 65.0% of households, whereas only one household reported having no medicines. Expired medicines and/or medicines with an unknown purpose were found in 41.6% of households. No household reported that medicines were accessible to children younger than 14 years. Inventories of stored medicines were obtained from 54 households (90.0%). Analgesics and antipyretics were present in 92.6% of households and were used for self-medication in 96.0% of them. Cough and cold preparations were found in 35.2% of households and used for self-medication in 94.7%. Antibiotics were present in 31.5% of households and used for self-medication in 52.9%, while anxiolytics were found in 16.7% of households and used for self-medication in 33.3%. Conclusions: Stocking medicine supplies and practicing self-medication are common among households of third-year medical and pharmacy students at the Faculty of Medicine, University of Rijeka. Analgesics and antipyretics were the most frequently stored medicines used for self-medication. The presence of expired medicines and the self-medication of prescription-only medicines highlight the need for greater emphasis on responsible self-medication, safe medicine storage, and rational medicine use within healthcare professions education. Full article