mocetinostat and Pain

COVID-19 as a viral disease has brought up the need to exercise more than before due to its physiological effects on health. Therefore, this study investigates the effect of 12-week of aerobic exercise on female students' hormone levels and lipid profile with polycystic ovary syndrome (PCOS) during the COVID-19 pandemic.. Using a 12-week quasi-experimental with pretest, posttest research design among 40 Iranian female students aged 18-14 with PCOS, we randomly allocated the participants to either an experimental (they performed aerobic exercises three 60-minute sessions per week at home using content production) or a control condition. Their anthropometric and blood samples (e.g., testosterone, estrogen, prolactin, and lipid profile) were taken in two stages before and after the training protocol.. Findings demonstrated that performing aerobic exercises is an effective and non-invasive method that could have a positive effect on young girls' PCOS during COVID-19 pandemic.. La pandémie de COVID-19, en tant que maladie virale, a fait ressortir la nécessité de faire de l’exercice plus que jamais en raison de ses effets physiologiques sur la santé. Par conséquent, cette étude examine l’effet de 12 semaines d’exercice aérobique sur les niveaux hormonaux et le profil lipidique d’étudiantes atteintes du syndrome d’ovaires polykystiques (SOPK) pendant la pandémie de COVID-19.. En utilisant un modèle de recherche quasi-expérimental de 12 semaines avec pré-test, post-test auprès de 40 étudiantes iraniennes âgées de 18 à 14 ans atteintes du SOPK, nous avons réparti au hasard les participantes entre une série expérimentale (elles ont effectué des exercices aérobiques à raison de trois séances de 60 minutes par semaine à la maison) et une série contrôle. Les échantillons anthropométriques et sanguins (testostérone, œstrogène, prolactine et profil lipidique) ont été prélevés en deux étapes, avant et après le protocole d’entraînement.. Les résultats ont démontré que la pratique d’exercices d’aérobic est une méthode efficace et non invasive qui pourrait avoir un effet positif sur le SOPK des jeunes filles pendant la pandémie de COVID-19.. Our research showed that even less than 5 GBq irradiation could induce a transient testicular dysfunction in the first 3 months of therapy, but it was mostly reversible after 12 months.. The online version contains supplementary material available at 10.1007/s13204-023-02822-5.. Embelin is predicted to have a high probability of immunotoxicity potential and affect drug metabolism by inhibiting CYP2D6. In addition, it affects food intake, weight gain, and the number of implantations in pregnant rats. Therefore, it is highly recommended not to take embelin and embelin-rich plants during pregnancy. Further. The online version contains supplementary material available at 10.1007/s42965-023-00306-9.. The online version contains supplementary material available at 10.1007/s11696-023-02771-x.. The online version contains supplementary material available at 10.1007/s00477-023-02476-3.. This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.. Inflammation response do not seem to be enough to explain all the Essure-related adverse outcomes, suggesting the involvement of other biological mechanisms.. NCT03281564.. Inflammation and fibrosis are found in the surrounding tubal tissue around the Essure. Adult patients with BED with co-occurring obesity who have good responses to acute treatment with naltrexone/bupropion should be offered maintenance treatment with naltrexone/bupropion.. dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.. Inverted microscopy showed that compared with the NC group, the OGD/R group had poor cell status, swollen cytosol, visible cell lysis fragments and significantly lower cell activity [(49.1±2.7)% vs. (100.0±9.7)%, P < 0.01]; compared with the OGD/R group, the HW group had improved cell status and remarkably higher cell activity [(63.3±1.8)% vs. (49.1±2.7)%, P < 0.01]. Transmission electron microscopy showed that the neuronal nuclear membrane of cells in the OGD/R group was lysed and a higher number of autophagic lysosomes were visible compared with the NC group; compared with the OGD/R group, the neuronal damage of cells in the HW group was reduced and the number of autophagic lysosomes was notably decreased. The results of immunofluorescence assay showed that the expressions of LC3 and Beclin-1 were outstandingly enhanced in the OGD/R group compared with the NC group, and the expressions of LC3 and Beclin-1 were markedly weakened in the HW group compared with the OGD/R group. Western blotting assay showed that the expressions were prominently higher in both LC3II/I and Beclin-1 in the OGD/R group compared with the NC group (LC3II/I: 1.44±0.05 vs. 0.37±0.03, Beclin-1/β-actin: 1.00±0.02 vs. 0.64±0.01, both P < 0.01); compared with the OGD/R group, the protein expression of both LC3II/I and Beclin-1 in the HW group cells were notably lower (LC3II/I: 0.54±0.02 vs. 1.44±0.05, Beclin-1/β-actin: 0.83±0.07 vs. 1.00±0.02, both P < 0.01).. Hydrogen-rich water has a significant protective effect on OGD/R-causing HT22 cell injury, and the mechanism may be related to the inhibition of autophagy.. The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.. For individuals ≥75 years, plasma Aβ42 and P-tau181 might not be associated with cognitive impairment, and MRI parameters, including PVWMH, LVBI and cortical atrophy, are related to CI. The cognitive statuses of people over 75 years old were used as the endpoint event in this study. Therefore, it can be considered that these MRI markers might have more important clinical significance for early assessment and dynamic observation, but more studies are still needed to verify this hypothesis.. We recommend using the Art/Zn complex owing to its moderate inhibitory and antiviral effects against the SARS-CoV-2 with a low cytotoxic effect on host (Vero E6) cells. We suggest conducting further prospective studies to investigate the biological effects of Art/Zn in animal models at different concentrations for testing its clinical efficacy and safety in inhibiting SARS-CoV-2 activities.. The R/T sequence resulted in a significantly longer OS and PFS and improved disease control compared with the reverse sequence. R and T given not sequentially have similar impacts on survival. More data are needed to define the best sequence and to explore the efficacy of sequential (T/R or R/T) treatment combined with molecular-targeted drugs.

Topics: Actin Cytoskeleton; Actins; Adaptor Proteins, Signal Transducing; Adenocarcinoma; Adenosine Triphosphate; Adsorption; Adult; Africa, Eastern; Aged; Air Pollutants; Air Pollution; Air Pollution, Indoor; Alcohol Drinking; Allergens; Alzheimer Disease; Amyotrophic Lateral Sclerosis; Animals; Anti-Bacterial Agents; Antibodies; Antibodies, Immobilized; Antigen Presentation; Antigens, CD; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Aptamers, Nucleotide; Asthma; Asthma, Exercise-Induced; Atrophy; Autophagy; Azoospermia; Bacillus cereus; Bacterial Infections; Beclin-1; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biofouling; Biological Monitoring; Biomarkers; Biomarkers, Tumor; Biosensing Techniques; Blastocyst; Bone Neoplasms; Bone Regeneration; Bronchoconstriction; Burkitt Lymphoma; C9orf72 Protein; Campylobacter; Campylobacter Infections; Campylobacter jejuni; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Pancreatic Ductal; Carcinoma, Squamous Cell; Cardiomyopathies; Caregivers; Carmine; Case-Control Studies; Catalysis; Cattle; Cause of Death; CCAAT-Enhancer-Binding Protein-alpha; CD8-Positive T-Lymphocytes; Cefepime; Cell Differentiation; Cell Line, Tumor; Cell Nucleus; Cell Transdifferentiation; Chelating Agents; Chemical and Drug Induced Liver Injury, Chronic; Chemoradiotherapy, Adjuvant; Child; Child, Preschool; China; Chlorquinaldol; Cholangiocarcinoma; Cholera; Chromatin; Clinical Trials as Topic; Cognitive Dysfunction; Cohort Studies; Colonic Neoplasms; Colorectal Neoplasms; Colorimetry; Cooking; Coordination Complexes; COVID-19; Creatinine; CRISPR-Cas Systems; Critical Care; Critical Illness; Cross-Sectional Studies; Cryopreservation; Cryoprotective Agents; Cysteine; Cytokines; Device Removal; Diet; Diet, High-Fat; Diet, Mediterranean; Dietary Supplements; Dimethyl Sulfoxide; Dipeptides; Disease Models, Animal; Dithiothreitol; DNA; DNA Repeat Expansion; DNA, Bacterial; DNA, Complementary; Dopamine; Electrochemical Techniques; Electrodes; Endocannabinoids; Environmental Exposure; Environmental Monitoring; Environmental Pollutants; Enzyme-Linked Immunosorbent Assay; Erlotinib Hydrochloride; Escherichia coli; Escherichia coli O157; Esophageal Neoplasms; Esophagitis, Peptic; Ethylene Glycol; Europium; Exanthema; Fallopian Tubes; Feces; Female; Fertilization in Vitro; Fluoresceins; Fluorescent Dyes; Follicle Stimulating Hormone; Follow-Up Studies; Food Microbiology; Forced Expiratory Volume; Forkhead Transcription Factors; Frontotemporal Dementia; G-Quadruplexes; Galactose; Gastroenteritis; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Neoplasms; Gastrointestinal Tract; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genital Neoplasms, Female; Genome-Wide Association Study; Genome, Viral; Genomics; Genotype; Glucose; Glutathione; Glycerol; Gold; Graphite; GTPase-Activating Proteins; Heat-Shock Proteins; Heme Oxygenase-1; Hepacivirus; Hepatitis C; Hepatocytes; Histamine; Histocompatibility Antigens Class II; Hoarseness; Hospice and Palliative Care Nursing; Humans; Hydrogen; Hydrogen Peroxide; Hydrogen Sulfide; Hydroxybenzoates; Hydroxyl Radical; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperthermia, Induced; Hysteroscopy; Immunoassay; Indigo Carmine; Inflammation; Inflammatory Bowel Diseases; Insulin Resistance; Intensive Care Units; Interleukin-11; Interleukin-6; Interleukins; Iodine Radioisotopes; Iran; Iridium; Islets of Langerhans; Kinetics; Lactation; Lactobacillus; Lactobacillus plantarum; Lamins; Latin America; Lead; Lectins; Leukopenia; Ligands; Limit of Detection; Lipopolysaccharides; Lipoprotein Lipase; Liver; Liver Cirrhosis; Liver Neoplasms; Lolium; Luminescent Measurements; Luminol; Lung; Luteinizing Hormone; Macrophages; Magnetic Phenomena; Magnetic Resonance Imaging; Male; Malnutrition; Maltose; Manganese Compounds; Maternal Nutritional Physiological Phenomena; Melatonin; Metabolic Engineering; Metal Nanoparticles; Metallocenes; Metaplasia; Methicillin-Resistant Staphylococcus aureus; Methylation; Mevalonic Acid; Mexico; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microbial Sensitivity Tests; Microbiota; MicroRNAs; Milk; Mitomycin; Molecular Diagnostic Techniques; Molecular Docking Simulation; Monte Carlo Method; Moringa oleifera; Multiple Sclerosis; Muscle Strength; Muscle, Skeletal; Nanocomposites; Nanotubes, Carbon; Neoadjuvant Therapy; Neoplasms; Neurodegenerative Diseases; Neurotransmitter Agents; NF-E2-Related Factor 2; Nickel; Nitrogen Dioxide; Non-alcoholic Fatty Liver Disease; Nucleic Acid Amplification Techniques; Nucleic Acid Hybridization; Nucleocapsid Proteins; Nutritional Status; Obesity; Osteogenesis; Osteosarcoma; Oxidation-Reduction; Oxides; Oxygen; Oxyquinoline; Pain; Palliative Care; Pancreatic Neoplasms; Pandemics; Particulate Matter; Peroxidase; Peroxidases; Phagocytosis; Phaseolus; Photothermal Therapy; Point-of-Care Systems; Polyethyleneimine; Polymers; Polymorphism, Single Nucleotide; Polysomnography; Postoperative Complications; Pregnancy; Pregnant Women; Prenatal Exposure Delayed Effects; Prevalence; Printing, Three-Dimensional; Probability; Probiotics; Prognosis; Prophages; Prospective Studies; Proteomics; Proto-Oncogene Proteins; Pseudomonas aeruginosa; Pseudomonas putida; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Pyridines; Pyrroles; Quality of Life; Quinolones; Rabbits; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Receptors, Histamine; Receptors, Histamine H2; Recombinases; Rectal Neoplasms; Reperfusion Injury; Respiration; Respiratory Function Tests; Respiratory Rate; Respiratory Sounds; Retrospective Studies; rho GTP-Binding Proteins; Risk Assessment; Risk Factors; RNA; RNA, Messenger; RNA, Ribosomal, 16S; Robotic Surgical Procedures; Running; Rural Population; Saccharomyces cerevisiae; Salpingectomy; Sarcopenia; SARS-CoV-2; Seeds; Semen; Sensitivity and Specificity; Sepsis; Shock, Septic; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Skin Neoplasms; Sleep Apnea, Obstructive; Soil; Spain; Spectrum Analysis, Raman; Sperm Retrieval; Spermatozoa; Spirometry; Staphylococcus aureus; STAT3 Transcription Factor; Stereoisomerism; Sterilization, Tubal; Stroke Volume; Sulfadiazine; Sulfites; Superoxide Dismutase; Surface Plasmon Resonance; tau Proteins; Testis; Testosterone; Thioredoxin-Disulfide Reductase; Thyroid Neoplasms; Thyroidectomy; Trans-Activators; Transcription Factor AP-1; Treatment Outcome; Triazoles; Triclosan; Trifluridine; Tumor Microenvironment; Tumor Necrosis Factor-alpha; United States; Uracil; Vagina; Vegetables; Ventricular Function, Left; Ventricular Pressure; Vibrio cholerae; Vietnam; Virulence; Vital Capacity; Vitrification; Walking; Water; Water Pollutants, Radioactive; Whole Genome Sequencing; Wind; YAP-Signaling Proteins; Zeolites; Zinc Oxide

COVID-19 as a viral disease has brought up the need to exercise more than before due to its physiological effects on health. Therefore, this study investigates the effect of 12-week of aerobic exercise on female students' hormone levels and lipid profile with polycystic ovary syndrome (PCOS) during the COVID-19 pandemic.. Using a 12-week quasi-experimental with pretest, posttest research design among 40 Iranian female students aged 18-14 with PCOS, we randomly allocated the participants to either an experimental (they performed aerobic exercises three 60-minute sessions per week at home using content production) or a control condition. Their anthropometric and blood samples (e.g., testosterone, estrogen, prolactin, and lipid profile) were taken in two stages before and after the training protocol.. Findings demonstrated that performing aerobic exercises is an effective and non-invasive method that could have a positive effect on young girls' PCOS during COVID-19 pandemic.. La pandémie de COVID-19, en tant que maladie virale, a fait ressortir la nécessité de faire de l’exercice plus que jamais en raison de ses effets physiologiques sur la santé. Par conséquent, cette étude examine l’effet de 12 semaines d’exercice aérobique sur les niveaux hormonaux et le profil lipidique d’étudiantes atteintes du syndrome d’ovaires polykystiques (SOPK) pendant la pandémie de COVID-19.. En utilisant un modèle de recherche quasi-expérimental de 12 semaines avec pré-test, post-test auprès de 40 étudiantes iraniennes âgées de 18 à 14 ans atteintes du SOPK, nous avons réparti au hasard les participantes entre une série expérimentale (elles ont effectué des exercices aérobiques à raison de trois séances de 60 minutes par semaine à la maison) et une série contrôle. Les échantillons anthropométriques et sanguins (testostérone, œstrogène, prolactine et profil lipidique) ont été prélevés en deux étapes, avant et après le protocole d’entraînement.. Les résultats ont démontré que la pratique d’exercices d’aérobic est une méthode efficace et non invasive qui pourrait avoir un effet positif sur le SOPK des jeunes filles pendant la pandémie de COVID-19.. Our research showed that even less than 5 GBq irradiation could induce a transient testicular dysfunction in the first 3 months of therapy, but it was mostly reversible after 12 months.. The online version contains supplementary material available at 10.1007/s13204-023-02822-5.. Embelin is predicted to have a high probability of immunotoxicity potential and affect drug metabolism by inhibiting CYP2D6. In addition, it affects food intake, weight gain, and the number of implantations in pregnant rats. Therefore, it is highly recommended not to take embelin and embelin-rich plants during pregnancy. Further. The online version contains supplementary material available at 10.1007/s42965-023-00306-9.. The online version contains supplementary material available at 10.1007/s11696-023-02771-x.. The online version contains supplementary material available at 10.1007/s00477-023-02476-3.. This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.. Inflammation response do not seem to be enough to explain all the Essure-related adverse outcomes, suggesting the involvement of other biological mechanisms.. NCT03281564.. Inflammation and fibrosis are found in the surrounding tubal tissue around the Essure. Adult patients with BED with co-occurring obesity who have good responses to acute treatment with naltrexone/bupropion should be offered maintenance treatment with naltrexone/bupropion.. dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.. Inverted microscopy showed that compared with the NC group, the OGD/R group had poor cell status, swollen cytosol, visible cell lysis fragments and significantly lower cell activity [(49.1±2.7)% vs. (100.0±9.7)%, P < 0.01]; compared with the OGD/R group, the HW group had improved cell status and remarkably higher cell activity [(63.3±1.8)% vs. (49.1±2.7)%, P < 0.01]. Transmission electron microscopy showed that the neuronal nuclear membrane of cells in the OGD/R group was lysed and a higher number of autophagic lysosomes were visible compared with the NC group; compared with the OGD/R group, the neuronal damage of cells in the HW group was reduced and the number of autophagic lysosomes was notably decreased. The results of immunofluorescence assay showed that the expressions of LC3 and Beclin-1 were outstandingly enhanced in the OGD/R group compared with the NC group, and the expressions of LC3 and Beclin-1 were markedly weakened in the HW group compared with the OGD/R group. Western blotting assay showed that the expressions were prominently higher in both LC3II/I and Beclin-1 in the OGD/R group compared with the NC group (LC3II/I: 1.44±0.05 vs. 0.37±0.03, Beclin-1/β-actin: 1.00±0.02 vs. 0.64±0.01, both P < 0.01); compared with the OGD/R group, the protein expression of both LC3II/I and Beclin-1 in the HW group cells were notably lower (LC3II/I: 0.54±0.02 vs. 1.44±0.05, Beclin-1/β-actin: 0.83±0.07 vs. 1.00±0.02, both P < 0.01).. Hydrogen-rich water has a significant protective effect on OGD/R-causing HT22 cell injury, and the mechanism may be related to the inhibition of autophagy.. The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.. For individuals ≥75 years, plasma Aβ42 and P-tau181 might not be associated with cognitive impairment, and MRI parameters, including PVWMH, LVBI and cortical atrophy, are related to CI. The cognitive statuses of people over 75 years old were used as the endpoint event in this study. Therefore, it can be considered that these MRI markers might have more important clinical significance for early assessment and dynamic observation, but more studies are still needed to verify this hypothesis.. We recommend using the Art/Zn complex owing to its moderate inhibitory and antiviral effects against the SARS-CoV-2 with a low cytotoxic effect on host (Vero E6) cells. We suggest conducting further prospective studies to investigate the biological effects of Art/Zn in animal models at different concentrations for testing its clinical efficacy and safety in inhibiting SARS-CoV-2 activities.. The R/T sequence resulted in a significantly longer OS and PFS and improved disease control compared with the reverse sequence. R and T given not sequentially have similar impacts on survival. More data are needed to define the best sequence and to explore the efficacy of sequential (T/R or R/T) treatment combined with molecular-targeted drugs.

Topics: Actin Cytoskeleton; Actins; Adaptor Proteins, Signal Transducing; Adenocarcinoma; Adenosine Triphosphate; Adsorption; Adult; Africa, Eastern; Aged; Air Pollutants; Air Pollution; Air Pollution, Indoor; Alcohol Drinking; Allergens; Alzheimer Disease; Amyotrophic Lateral Sclerosis; Animals; Anti-Bacterial Agents; Antibodies; Antibodies, Immobilized; Antigen Presentation; Antigens, CD; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Aptamers, Nucleotide; Asthma; Asthma, Exercise-Induced; Atrophy; Autophagy; Azoospermia; Bacillus cereus; Bacterial Infections; Beclin-1; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biofouling; Biological Monitoring; Biomarkers; Biomarkers, Tumor; Biosensing Techniques; Blastocyst; Bone Neoplasms; Bone Regeneration; Bronchoconstriction; Burkitt Lymphoma; C9orf72 Protein; Campylobacter; Campylobacter Infections; Campylobacter jejuni; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Pancreatic Ductal; Carcinoma, Squamous Cell; Cardiomyopathies; Caregivers; Carmine; Case-Control Studies; Catalysis; Cattle; Cause of Death; CCAAT-Enhancer-Binding Protein-alpha; CD8-Positive T-Lymphocytes; Cefepime; Cell Differentiation; Cell Line, Tumor; Cell Nucleus; Cell Transdifferentiation; Chelating Agents; Chemical and Drug Induced Liver Injury, Chronic; Chemoradiotherapy, Adjuvant; Child; Child, Preschool; China; Chlorquinaldol; Cholangiocarcinoma; Cholera; Chromatin; Clinical Trials as Topic; Cognitive Dysfunction; Cohort Studies; Colonic Neoplasms; Colorectal Neoplasms; Colorimetry; Cooking; Coordination Complexes; COVID-19; Creatinine; CRISPR-Cas Systems; Critical Care; Critical Illness; Cross-Sectional Studies; Cryopreservation; Cryoprotective Agents; Cysteine; Cytokines; Device Removal; Diet; Diet, High-Fat; Diet, Mediterranean; Dietary Supplements; Dimethyl Sulfoxide; Dipeptides; Disease Models, Animal; Dithiothreitol; DNA; DNA Repeat Expansion; DNA, Bacterial; DNA, Complementary; Dopamine; Electrochemical Techniques; Electrodes; Endocannabinoids; Environmental Exposure; Environmental Monitoring; Environmental Pollutants; Enzyme-Linked Immunosorbent Assay; Erlotinib Hydrochloride; Escherichia coli; Escherichia coli O157; Esophageal Neoplasms; Esophagitis, Peptic; Ethylene Glycol; Europium; Exanthema; Fallopian Tubes; Feces; Female; Fertilization in Vitro; Fluoresceins; Fluorescent Dyes; Follicle Stimulating Hormone; Follow-Up Studies; Food Microbiology; Forced Expiratory Volume; Forkhead Transcription Factors; Frontotemporal Dementia; G-Quadruplexes; Galactose; Gastroenteritis; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Neoplasms; Gastrointestinal Tract; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genital Neoplasms, Female; Genome-Wide Association Study; Genome, Viral; Genomics; Genotype; Glucose; Glutathione; Glycerol; Gold; Graphite; GTPase-Activating Proteins; Heat-Shock Proteins; Heme Oxygenase-1; Hepacivirus; Hepatitis C; Hepatocytes; Histamine; Histocompatibility Antigens Class II; Hoarseness; Hospice and Palliative Care Nursing; Humans; Hydrogen; Hydrogen Peroxide; Hydrogen Sulfide; Hydroxybenzoates; Hydroxyl Radical; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperthermia, Induced; Hysteroscopy; Immunoassay; Indigo Carmine; Inflammation; Inflammatory Bowel Diseases; Insulin Resistance; Intensive Care Units; Interleukin-11; Interleukin-6; Interleukins; Iodine Radioisotopes; Iran; Iridium; Islets of Langerhans; Kinetics; Lactation; Lactobacillus; Lactobacillus plantarum; Lamins; Latin America; Lead; Lectins; Leukopenia; Ligands; Limit of Detection; Lipopolysaccharides; Lipoprotein Lipase; Liver; Liver Cirrhosis; Liver Neoplasms; Lolium; Luminescent Measurements; Luminol; Lung; Luteinizing Hormone; Macrophages; Magnetic Phenomena; Magnetic Resonance Imaging; Male; Malnutrition; Maltose; Manganese Compounds; Maternal Nutritional Physiological Phenomena; Melatonin; Metabolic Engineering; Metal Nanoparticles; Metallocenes; Metaplasia; Methicillin-Resistant Staphylococcus aureus; Methylation; Mevalonic Acid; Mexico; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microbial Sensitivity Tests; Microbiota; MicroRNAs; Milk; Mitomycin; Molecular Diagnostic Techniques; Molecular Docking Simulation; Monte Carlo Method; Moringa oleifera; Multiple Sclerosis; Muscle Strength; Muscle, Skeletal; Nanocomposites; Nanotubes, Carbon; Neoadjuvant Therapy; Neoplasms; Neurodegenerative Diseases; Neurotransmitter Agents; NF-E2-Related Factor 2; Nickel; Nitrogen Dioxide; Non-alcoholic Fatty Liver Disease; Nucleic Acid Amplification Techniques; Nucleic Acid Hybridization; Nucleocapsid Proteins; Nutritional Status; Obesity; Osteogenesis; Osteosarcoma; Oxidation-Reduction; Oxides; Oxygen; Oxyquinoline; Pain; Palliative Care; Pancreatic Neoplasms; Pandemics; Particulate Matter; Peroxidase; Peroxidases; Phagocytosis; Phaseolus; Photothermal Therapy; Point-of-Care Systems; Polyethyleneimine; Polymers; Polymorphism, Single Nucleotide; Polysomnography; Postoperative Complications; Pregnancy; Pregnant Women; Prenatal Exposure Delayed Effects; Prevalence; Printing, Three-Dimensional; Probability; Probiotics; Prognosis; Prophages; Prospective Studies; Proteomics; Proto-Oncogene Proteins; Pseudomonas aeruginosa; Pseudomonas putida; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Pyridines; Pyrroles; Quality of Life; Quinolones; Rabbits; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Receptors, Histamine; Receptors, Histamine H2; Recombinases; Rectal Neoplasms; Reperfusion Injury; Respiration; Respiratory Function Tests; Respiratory Rate; Respiratory Sounds; Retrospective Studies; rho GTP-Binding Proteins; Risk Assessment; Risk Factors; RNA; RNA, Messenger; RNA, Ribosomal, 16S; Robotic Surgical Procedures; Running; Rural Population; Saccharomyces cerevisiae; Salpingectomy; Sarcopenia; SARS-CoV-2; Seeds; Semen; Sensitivity and Specificity; Sepsis; Shock, Septic; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Skin Neoplasms; Sleep Apnea, Obstructive; Soil; Spain; Spectrum Analysis, Raman; Sperm Retrieval; Spermatozoa; Spirometry; Staphylococcus aureus; STAT3 Transcription Factor; Stereoisomerism; Sterilization, Tubal; Stroke Volume; Sulfadiazine; Sulfites; Superoxide Dismutase; Surface Plasmon Resonance; tau Proteins; Testis; Testosterone; Thioredoxin-Disulfide Reductase; Thyroid Neoplasms; Thyroidectomy; Trans-Activators; Transcription Factor AP-1; Treatment Outcome; Triazoles; Triclosan; Trifluridine; Tumor Microenvironment; Tumor Necrosis Factor-alpha; United States; Uracil; Vagina; Vegetables; Ventricular Function, Left; Ventricular Pressure; Vibrio cholerae; Vietnam; Virulence; Vital Capacity; Vitrification; Walking; Water; Water Pollutants, Radioactive; Whole Genome Sequencing; Wind; YAP-Signaling Proteins; Zeolites; Zinc Oxide

There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.

Topics: Acetylcysteine; Adult; Antioxidants; Ascorbic Acid; Bleomycin; Creatine Kinase; Dinoprost; Double-Blind Method; Exercise; F2-Isoprostanes; Glutathione Peroxidase; Humans; Interleukin-6; Iron; L-Lactate Dehydrogenase; Lipid Peroxidation; Lipid Peroxides; Male; Muscle, Skeletal; Myoglobin; Myositis; Oxidative Stress; Pain; Peroxidase; Placebos; Superoxide Dismutase

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Cyclooxygenase 2; Edema; Female; Inflammation; Mice; Pain; Peroxidase; Piperazines; Plant Extracts; Pleurisy; Zymosan

Gout is an inflammatory disease characterized by the accumulation of monosodium urate crystals (MSU) in the joints, leading to severe pain and inflammation. Stephalagine is a Brazilian Savanna aporphine alkaloid isolated from Annona crassiflora Mart. Fruit peel, that has been popularly used to treat rheumatism and have been described with antinociceptive properties. However, no studies evaluated the possible therapeutic properties of stephalagine in arthritic pain.. To evaluate the possible antinociceptive and anti-inflammatory effects of stephalagine in an acute gout attack in mice.. Adult male wild type C57BL/6/J/UFU mice (20-25 g) were used (process number 018/17). The treated group received stephalagine (1 mg/kg, by gavage) and the vehicle group received saline (10 mL/kg, by gavage), both 1 h before the MSU crystals (100 μg/ankle joint) administration. All groups were analyzed for mechanical allodynia, thermal hyperalgesia, overt pain-like behaviors, and edema development at 2, 4, 6 and 24 h after injections. Synovial fluid and the ankle articulation from the injected joint were collected 4 h after administrations for myeloperoxidase enzyme activity, IL-1β measurement, and histological analysis.. Stephalagine had a significant antinociceptive effect on mechanical allodynia, when compared to vehicle group at 2-24 h after intra-articular injection of MSU and 2 h for spontaneous and cold thermal sensitivity. Stephalagine was also able to significantly reduce the articular edema (45 ± 1%), the activity of the myeloperoxidase enzyme (37 ± 6%), and IL-1β levels (43 ± 3%). The histological analysis confirms that stephalagine dramatically reduced the number of infiltrating inflammatory cells (75 ± 6%) in MSU injected animals. Also, stephalagine treatment did not alter the uric acid levels, xanthine oxidase activity, AST and ALT activities, urea and creatinine levels, neither cause any macroscopic changes in the mice's weight, deformations, changes in the coat, or feces.. Stephalagine may be an alternative for the management of gout, once it was able to induce antinociceptive and anti-inflammatory effects without causing adverse effects on the evaluated parameters.

Topics: Alkaloids; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Aporphines; Arthritis, Gouty; Edema; Gout; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Pain; Peroxidase

Gedunin is a bioactive compound, obtained from Entandrophragma angolense (EA), which has limited therapeutic usefulness due to poor aqueous solubility and first-pass effects. Cyclodextrins are cyclic oligosaccharides that form complexes with poorly soluble compounds, thus enhancing their pharmacological activity. In this article, we evaluated the pharmacological activities of gedunin-2-hydroxypropyl-β-cyclodextrin complex (GCD) in rodents. The antinociceptive activity of GCD (50, 100, 200 mg/kg) and Gedunin (50mg/kg) was tested in acetic acid-induced writhing and formalin-induced paw licking in mice. The anti-inflammatory activity was investigated in carrageenan-induced paw oedema and air pouch inflammation models in rats. Leucocytes counts, Tumour Necrosis Factor-alpha (TNF-α) level, nitric oxide, malondialdehyde, reduced glutathione, and myeloperoxidase enzyme activities were assessed in the air pouch exudate. The GCD (200mg/kg) significantly decreased writhing response, reduced licking duration and decreased oedema compared with gedunin and control. Exudate volume and leucocyte count were significantly reduced by GCD (200 mg/kg), it decreased myeloperoxidase activity and inhibited TNF-α release. The carrageenan-induced GSH depletion, increased malondialdehyde and nitrite levels were significantly reversed by GCD (200 mg/kg) relative to gedunin and control.  The GCD complex demonstrated significant antinociceptive and anti-inflammatory activities relative to gedunin alone via mechanisms associated with inhibition of oxidative stress and inflammation in rodents.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Carrageenan; Edema; Inflammation; Limonins; Malondialdehyde; Mice; Pain; Peroxidase; Plant Extracts; Rats; Rodentia; Tumor Necrosis Factor-alpha

Sphagneticola trilobata (L.) Pruski is a plant species belonging to the Asteraceae family. Kaurenoid acid (KA) is a diterpene metabolite and one of the active ingredients of Sphagneticola trilobata (L.) Pruski. Extracts containing KA are used in traditional medicine to treat pain, inflammation, and infection.. The goal of the present study was to investigate the in vivo effects of KA (1-10 mg/kg, per oral gavage) upon LPS inoculation in mice by intraperitoneal (i.p.) or intraplantar (i.pl.; subcutaneous plantar injection) routes at the dose of 200 ng (200 μL or 25 μL, respectively).. In LPS paw inflammation, mechanical and thermal hyperalgesia MPO activity and oxidative imbalance (TBARS, GSH, ABTS and FRAP assays) were evaluated. In LPS peritonitis we evaluated leukocyte migration, cytokine production, oxidative stress, and NF-κB activation.. KA inhibited LPS-induced mechanical and thermal hyperalgesia, MPO activity and modulated redox status in the mice paw. Pre- and post-treatment with KA inhibited migration of neutrophils and monocytes in LPS peritonitis. KA inhibited the pro-inflammatory/hyperalgesic cytokine (e.g., TNF-α, IL-1β and IL-33) production while enhanced anti-inflammatory/analgesic cytokine IL-10 in peritoneal cavity. In agreement with the effect of KA over pro-inflammatory cytokines it inhibited oxidative stress (total ROS, superoxide production and superoxide positive cells) and NF-κB activation during peritonitis.. KA efficiently dampens LPS-induced peritonitis and hyperalgesia in vivo, suggesting it as a suitable candidate to control excessive inflammation and pain during gram-negative bacterial infections and bringing mechanistic explanation to the ethnopharmacological application of Sphagneticola trilobata (L.) Pruski in inflammation and infection.

Topics: Analgesics; Animals; Asteraceae; Diterpenes; Gene Expression Regulation; Hyperalgesia; Lipid Peroxidation; Lipopolysaccharides; Male; Mice; Molecular Structure; NF-kappa B; Pain; Peritonitis; Peroxidase

Palmitoylethanolamide (PEA), a fatty acid amide, has been widely investigated for its analgesic and anti-inflammatory properties. The ultra-micronized formulation of PEA (um-PEA), that has an enhanced rate of dissolution, is extensively used. Acetyl-l-carnitine (LAC), employed for the treatment of neuropathic pain in humans, is able to cause analgesia by up-regulating type-2 metabotropic glutamate (mGlu2) receptors. In the present study, we tested different associations of um-PEA, LAC and non-micronized PEA (non-m-PEA) in a rat model of carrageenan (CAR)-induced paw edema. Intraplantar injection of CAR into the hind paw of animals caused edema, thermal hyperalgesia, accumulation of infiltrating inflammatory cells and augmented myeloperoxidase (MPO) activity. All these parameters were decreased in a significantly manner by oral administration of a compound constituted by a mixture of um-PEA and LAC in relation 1:1 (5 mg/kg), but not with the association of single compounds administered one after the other. These findings showed the superior anti-inflammatory and anti-nociceptive action displayed by oral administration of um-PEA and LAC versus LAC plus, separate but consecutive, um-PEA in the rat paw CAR model of inflammatory pain.

Topics: Acetylcarnitine; Amides; Animals; Carrageenan; Cell Count; Cyclooxygenase 2; Disease Models, Animal; Edema; Ethanolamines; Hyperalgesia; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; Male; Mast Cells; Nitric Oxide Synthase Type II; Pain; Palmitic Acids; Peroxidase; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha

Knee osteoarthritis (OA) cause pain and edema, as well as unbalance between the production of reactive oxygen species and antioxidant activity. These problems interfere with the articular function, leading to a significant loss of life quality. Sida tuberculata R.E.Fr. is an herbaceous plant belonging to the Malvaceae family found in southern Brazil. This plant has traditionally been consumed as an aqueous extract and popularly used in the treatment of many diseases, with antioxidant and antimicrobial activity, reducing pain and inflammation.. To verify the effects of S. tuberculata extract obtained from leaves on oxidative, toxic and nociceptive parameters induced by knee OA in rats.. Aqueous extracts of S. tuberculata were evaluated under phytochemical analyses. Knee Osteoarthritis was induced in rats with monosodium iodoacetate (1.5 mg/50 μl) and treated with S. tuberculata extract. The animals were treated orally with 3 doses of S. tuberculata extract (STE): 1.5, 5 and 15 mg/ml, for 14 days. For biochemical analyses, the following tests were performed: lipid peroxidation, carbonylated protein content, superoxide dismutase activity, non-protein thiol levels and myeloperoxidase activity. For the evaluation of pain and edema we verify mechanical and thermal hyperalgesia, spontaneous pain observation and measurement of knee edema with a caliper. For histological evaluations, the animal knee joints were removed. For toxicity evaluation, the levels of aspartate aminotransferase, alanine aminotransferase and urea, as well as the relative weight of the organs were analyzed.. The S. tuberculata phytochemical analyses showed the majority peak corresponding to 20-hydroxyecdysone (20HE). The plant extract decreased damages related to oxidative stress in the blood serum (lipid peroxidation and carbonyl content) Overall, the STE 5 mg Group presented the greater statistical significance, in the blood serum samples, in relation to the other groups, being the most relevant result. The S. tuberculata groups presented pain decrease, lower neutrophil activity in the knee, and increased blood serum activity. The animals of S. tuberculata groups showed a decrease in mechanical hyperalgesia. The animals treated also presented lower scores for spontaneous pain. It was observed that the dose of 5 mg presented, once again, more expressive results, since the animals of this group had a higher frequency (greater number of days) with significant decrease of pain. In the histological analysis, in the STE 5 mg group, the articular cartilage lesions were observed at an intermediate point between the damage found in the MIA and Diclofenac groups. Besides that, the STE did not show significant changes in oxidative stress damage in liver and kidney samples. Blood serum samples did not indicate significant differences in liver and renal function. As well as, there were no differences in mean relative body weights in relation to control groups (Salina and MIA).. S. tuberculata reduced the damage due to oxidative stress and pain caused by knee osteoarthritis in rats. In addition, the extract presented no toxicity. Our results suggest that S. tuberculata seems to have a therapeutic potential in the osteoarthritis treatment.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cartilage, Articular; Edema; Knee Joint; Male; Malvaceae; Osteoarthritis, Knee; Oxidative Stress; Pain; Peroxidase; Plant Extracts; Rats, Wistar; Superoxide Dismutase

Vitamin D (VD3, cholecalciferol), besides its role on bone calcium homeostasis, has also been shown to present anti-inflammatory actions. The objectives of the present work were to further extend these findings, focusing onVD3action mechanisms at the molecular level and onits central and peripheral effects. For that, VD3 antinociceptive and mainly anti-inflammatory activities were evaluated by acute models of nociception (formalin test) and inflammation (carrageenan-induced paw edema), in mice pretreated orally for 7 days with VD3 (0.5 and 1.0 mg/kg). Afterwards, the edematous paws were evaluated by immunohistochemical assays for TNF-alpha. In addition, brains from mice pretreated with VD3, at the same conditions, were harvested for iNOS andCOX-2 immunohistochemical (IHC) assays. The anti-inflammatory effect of VD3 on human neutrophil degranulation was evaluated by the release of myeloperoxidase (MPO) activity, as well as by the reactive oxygen species production. VD3 significantly reduced the licking time in the formalin test, at the second phase (inflammatory pain). VD3 also reduced the edema volume and the number of polymorphonuclear (PMN) cells, as well as the TNF-alpha expression in the edematous paws, compared with the control group. Furthermore, VD3 significantly decreased iNOS and COX-2 expressions in brain areas, such as hippocampus and prefrontal cortex, and inhibited the degranulation of activated neutrophils by the reduction of ROS production and MPO release. Based in these results, VD3 presents anti-inflammatory and antioxidative effects, manifested at peripheral and central sites as showed in the present work for the first time.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Carrageenan; Cyclooxygenase 2; Edema; Formaldehyde; Humans; Male; Mice; Neutrophils; Nitric Oxide Synthase Type II; Pain; Pain Measurement; Peroxidase; Reactive Oxygen Species; Vitamin D; Vitamins

Many injuries cause pain and inflammation, which are one of the major challenges for physicians. In this study, the analgesic and the anti-inflammatory effects of milnacipran were investigated on carrageenan-induced nociception and inflammation in male rats.. Pain and inflammation were induced by injection of λ-carrageenan (1% v/v) into the hind paw. Indomethacin (10 mg/kg: ip) or milnacipran (10, 20 and 40 mg/kg: ip) were administered 30 min before carrageenan. Analgesia and inflammation were measured by hot plate and plethysmometer. Finally, lipid peroxidation, tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), myeloperoxidase (MPO) activity, nitric oxide (NO) and total antioxidant capacity (TAC) status evaluated in the hind paw tissue.. The results showed that carrageenan caused hyperalgesia and inflammation in the hind paw tissue. Milnacipran (20 and 40 mg/kg) significantly and dose-dependently attenuated (65 ± 3.2%; p ≤0.01 and 42 ± 6.2%; p ≤ 0.001, respectively) carrageenan-induced inflammation and significantly increased (p ≤ 0.001) nociception threshold. Also, milnacipran (20 and 40 mg/kg) significantly suppressed levels of malondialdehyde (MDA), NO (p ≤ 0.05), MPO activity, TNF-α, IL-1β and IL-6 (p ≤ 0.001) following carrageenan injection. Additionally, milnacipran (10, 20 and 40 mg/kg) significantly augmented (p ≤ 0.05) TAC status following carrageenan in the hind paw tissue.. In the present study, milnacipran showed anti-nociceptive and anti-inflammatory effects on carrageenan-induced hyperalgesia and inflammation in a dose-dependent manner. Milnacipran reduced inflammatory edema and increased the paw withdrawal threshold probably through suppression of MDA, NO, TNF-α, IL-1β, IL-6 and MPO activity, and increase of TAC status in the hind paw tissue. Therefore, milnacipran holds important potential as an anti-inflammatory and anti-nociceptive drug. Although, further clinical trials to confirm this issue, is required.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Cytokines; Disease Models, Animal; Edema; Hyperalgesia; Indomethacin; Inflammation; Interleukin-1beta; Interleukin-6; Male; Malondialdehyde; Milnacipran; Nitric Oxide; Nitrosative Stress; Oxidative Stress; Pain; Peroxidase; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The aim of this study was to synthesise the novel di-tert-butylphenol compound, 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxo-dihydropyrimidine-4,6(1H, 5H)-dione (LQFM218), and evaluate the potential anti-nociceptive and anti-inflammatory activities in acute (mice) models in vivo. The compound was tested on acute models of pain such as acetic acid-induced abdominal writhing, formalin-induced nociception and carrageenan-induced mechanical hyperalgesia. The anti-inflammatory activity was observed in paw oedema, carrageenan-induced pleurisy tests and inflammatory mediator quantification. Key findings: oral treatment with the LQFM218 (50, 100 or 200 mg/kg) reduced abdominal writhing (18.8%, 31.6% and 48.3%). The dose intermediate (100 mg/kg) reduced the nociception in the second phase of the formalin test (61.4%), and also showed anti-hyperalgic activity in carrageenan-induced mechanical hyperalgesia (until 42.3%). In acute inflammation models, the treatment of mice LQFM218 (100 mg/kg) reduced the paw oedema all the time (33.8%, 42.6%, 37.4% and 36%) and in pleurisy test reduced: polymorphonuclear cell migration (35.4%), myeloperoxidase activity (52.2%) and the levels of inflammatory mediators such as PGE

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Edema; Hyperalgesia; Inflammation Mediators; Male; Mice; Neutrophils; Pain; Pain Measurement; Peroxidase; Pleurisy

To investigate the role of IL-33 in gouty arthritis.. 174 Balb/c (wild-type) and 54 ST2. Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM.. Synovial fluid of gout patients showed higher IL-33 levels and neutrophil counts than osteoarthritis patients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1β and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1β and TNF-α, and BMDMs from ST2. IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus.

Topics: Animals; Arthritis, Gouty; Female; Humans; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-1beta; Interleukin-33; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Middle Aged; Neutrophil Infiltration; Pain; Peroxidase; Superoxides; Synovial Membrane; Uric Acid

This study investigated the gastroprotective effects of N-acetylcysteine (NAC) against indomethacin-induced gastric ulcer in rats. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg). 50 male albino rats were allocated into 5 equal groups: control group received normal saline orally, indomethacin group rats received normal saline orally for 5 days and indomethacin (50 mg/kg) on the last day, ranitidine group received ranitidine (reference drug) orally for 5 days (50 mg/kg) before receiving indomethacin (50 mg/kg) on the last day, and NAC groups received NAC orally at 300 and 500 mg/kg, respectively, for 5 days before receiving indomethacin (50 mg/kg) on the last day. Gastric tissue interleukin-1β (IL-1β), interferon-γ (IFN-γ), and caspase-3 levels were immunoassayed. Total thiol (T-SH), myeloperoxidase (MPO), and glucose-6-phosphate dehydrogenase (G6PD) were determined by spectrophotometry. Cytokine-induced neutrophil chemoattractant 2α (CINC-2α) gene expression was evaluated in addition to Bcl-2 immunohistochemistry. Pretreatment with NAC improved the inflammatory, apoptotic, and redox status in a dose-dependent manner particularly in NAC 500 mg/kg pretreated group. These results show a role for NAC in improving indomethacin-induced gastric ulceration via antioxidative, antiapoptotic, and anti-inflammatory interactive mechanisms.

Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Apoptosis; Caspase 3; Chemical and Drug Induced Liver Injury; Chemokines, CXC; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Gastric Mucosa; Glucosephosphate Dehydrogenase; Humans; Indomethacin; Interferon-gamma; Interleukin-1beta; Male; Oxidation-Reduction; Pain; Peroxidase; Proto-Oncogene Proteins c-bcl-2; Ranitidine; Rats; Rats, Wistar; Stomach Ulcer

This study investigated the effects of the long-term dietary fish oil supplementation or the acute administration of the omega-3 fatty acid docosahexaenoic acid (DHA) in the mouse hemorrhagic cystitis (HC) induced by the anticancer drug cyclophosphamide (CYP). HC was induced in mice by a single CYP injection (300mg/kg ip). Animals received four different diets containing 10% and 20% of corn or fish oil, during 21days. Separated groups received DHA by ip (1μmol/kg) or intrathecal (i.t.; 10μg/site) routes, 1h or 15min before CYP. The behavioral tests (spontaneous nociception and mechanical allodynia) were carried out from 1h to 6h following CYP injection. Bladder inflammatory changes, blood cell counts and serum cytokines were evaluated after euthanasia (at 6h). Immunohistochemistry analysis was performed for assessing spinal astrocyte and microglia activation or GPR40/FFAR1 expression. Either fish oil supplementation or DHA treatment (ip and i.t.) markedly prevented visceral pain, without affecting CYP-evoked bladder inflammatory changes. Moreover, systemic DHA significantly prevented the neutrophilia/lymphopenia caused by CYP, whereas this fatty acid did not significantly affect serum cytokines. DHA also modulated the spinal astrocyte activation and the GPR40/FFAR1 expression. The supplementation with fish oil enriched in omega-3 fatty acids or parenteral DHA might be interesting nutritional approaches for cancer patients under chemotherapy schemes with CYP.

Topics: Animals; Cyclophosphamide; Cystitis; Fatty Acids, Omega-3; Hemorrhage; Male; Mice; Pain; Peroxidase; Urinary Bladder

Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti-inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti-inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan-induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose-dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis 3-ethylbenzothiazoline 6-sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50 : 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Female; Free Radical Scavengers; Inflammation; Male; Mice; Pain; Peroxidase; Phytotherapy; Plant Components, Aerial; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Urticaceae

Neural cross-sensitization has been postulated as a mechanism underlying overlaps of chronic pelvic pain disorders such as bladder pain syndrome/interstitial cystitis (BPS/IC) and irritable bowel syndrome (IBS). Animals with experimental colitis have been used to study the underlying mechanisms for overlapped pelvic pain symptoms, and shown to exhibit bladder overactivity evidenced by frequent voiding; however, it has not directly been evaluated whether pain sensation derived from the lower urinary tract is enhanced in colitis models. Also, the cross-sensitization between the colon and urethra has not been studied previously. In the present study, we therefore investigated pain behaviors induced by nociceptive stimuli in the lower urinary tract and the involvement of C-fiber afferent pathways using rats with colitis induced by intracolonic application of 2,4,6-trinitrobenzenesulfonic acid (TNBS). In TNBS-induced colitis rats at 10 days, intravesical application of resiniferatoxin (RTx) induced a significantly greater number of episodes of both licking and freezing behaviors, which were reduced by capsaicin-sensitive C-fiber afferent desensitization. Histochemical studies using fluorescent dye tracers injected into the colon, bladder or urethra showed that dichotomized afferent neurons comprised 6.9-14.5% of L1, L6 and S1 dorsal root ganglion (DRG) neurons innervating the colon or the lower urinary tract. Transient receptor potential vanilloid 1 (TRPV1) mRNA expression was significantly increased in, the bladder, urethra and S1 DRG in colitis rats. An increase in myeloperoxidase (MPO) activity was found in the colon, but not in the bladder or urethra after intracolonic TNBS treatment. These results indicate that TNBS-induced colitis increased pain sensitivity in the bladder and urethra via activation of C-fiber afferent pathways due to colon-to-bladder and colon-to-urethral cross-sensitization, suggesting the contribution of pelvic organ cross-sensitization mechanisms to overlapped pain symptoms in BPS/IC and IBS.

Topics: Animals; Colitis; Colon; Disease Models, Animal; Diterpenes; Female; Freezing Reaction, Cataleptic; Ganglia, Spinal; Grooming; Neurons, Afferent; Pain; Peroxidase; Rats, Sprague-Dawley; RNA, Messenger; Trinitrobenzenesulfonic Acid; TRPV Cation Channels; Urethra; Urinary Bladder

Inflammatory hyperalgesia is a complex process that depends on the sensitization of primary nociceptive neurons triggered by proinflammatory mediators, such as interleukin 1β (IL-1β). Recently, the peripheral activation of caspase-1 (previously known as IL-1β-converting enzyme) was implicated in the induction of acute inflammatory pain by promoting the processing of IL-1β from its precursor form, pro-IL-1β. Caspase-1 activation in several systems requires the assembly of an intracellular molecular platform called an inflammasome. Inflammasomes consist of 1 nucleotide-binding oligomerization domain-like receptor (NLR), the adapter molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), and caspase-1. NLRP3 and NLRC4 inflammasomes are well described. However, the identity of the inflammasome that is involved in the peripheral activation of caspase-1 that accounts for acute inflammatory hyperalgesia has not been described. The present findings demonstrated that mice deficient in NLRC4 or ASC, but not in NLRP3, present reduced mechanical and thermal acute inflammatory hyperalgesia induced by carrageenan. The reduced hyperalgesia was accompanied by significant impairments in the levels of mature forms of IL-1β (p17) and caspase-1 (p20) compared to wild-type mice at the inflammatory site. Therefore, these results identified the inflammasome components NLRC4 and ASC as the molecular platform involved in the peripheral activation of caspase-1 and IL-1β maturation, which are responsible for the induction of acute inflammatory pain. In conclusion, our study provides new therapeutic targets for the control of acute inflammatory pain.

Topics: Animals; Apoptosis Regulatory Proteins; Calcium-Binding Proteins; Caspase 1; Caspases; Caspases, Initiator; Cytokines; Dinoprostone; Disease Models, Animal; Gene Expression Regulation; Hyperalgesia; Inflammation; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pain; Pain Measurement; Pain Threshold; Peroxidase; Receptors, Interleukin-1 Type I

In response to lipopolysaccharide (LPS), tissue resident macrophages and recruited neutrophils produce inflammatory mediators through activation of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. These mediators include inflammatory cytokines and reactive oxygen species that, in turn, sensitize nociceptors and lead to inflammatory pain. Vinpocetine is a nootropic drug widely used to treat cognitive and neurovascular disorders, and more recently its anti-inflammatory properties through inhibition of NF-κB activation have been described. In the present study, we used the intraplantar and intraperitoneal LPS stimulus in mice to investigate the effects of vinpocetine pre-treatment (3, 10, or 30mg/kg by gavage) in hyperalgesia, leukocyte recruitment, oxidative stress, and pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-33). LPS-induced NF-κB activation and cytokine production were investigated using RAW 264.7 macrophage cell in vitro. Vinpocetine (30mg/kg) significantly reduces hyperalgesia to mechanical and thermal stimuli, and myeloperoxidase (MPO) activity (a neutrophil marker) in the plantar paw skin, and also inhibits neutrophil and mononuclear cell recruitment, superoxide anion and nitric oxide production, oxidative stress, and cytokine production (TNF-α, IL-1β and IL-33) in the peritoneal cavity. At least in part, these effects seem to be mediated by direct effects of vinpocetine on macrophages, since it inhibited the production of the same cytokines (TNF-α, IL-1β and IL-33) and the NF-κB activation in LPS-stimulated RAW 264.7 macrophages. Our results suggest that vinpocetine represents an important therapeutic approach to treat inflammation and pain induced by a gram-negative bacterial component by targeting NF-κB activation and NF-κB-related cytokine production in macrophages.

Topics: Animals; Cytokines; Lipopolysaccharides; Macrophages; Male; Mice; Neutrophils; NF-kappa B; Oxidative Stress; Pain; Peritoneal Cavity; Peroxidase; Vinca Alkaloids

Bosentan is a mixed endothelin receptor antagonist widely used to treat patients with pulmonary arterial hypertension, and the emerging literature suggests bosentan as a potent anti-inflammatory drug. Superoxide anion is produced in large amounts during inflammation, stimulates cytokine production, and thus contributes to inflammation and pain. However, it remains to be determined whether endothelin contributes to the inflammatory response triggered by the superoxide anion. The present study investigated the effects of bosentan in a mouse model of inflammation and pain induced by potassium superoxide, a superoxide anion donor. Male Swiss mice were treated with bosentan (10-100 mg/kg) by oral gavage, 1 h before potassium superoxide injection, and the inflammatory response was evaluated locally and at spinal cord (L4-L6) levels. Bosentan (100 mg/kg) inhibited superoxide anion-induced mechanical and thermal hyperalgesia, overt pain-like behavior (abdominal writhings, paw flinching, and licking), paw edema, myeloperoxidase activity (neutrophil marker) in the paw skin, and leukocyte recruitment in the peritoneal cavity. Bosentan also inhibited superoxide anion-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) production, while it enhanced IL-10 production in the paw skin and spinal cord. Bosentan inhibited the reduction of antioxidant capacity (reduced glutathione, ferric reducing antioxidant power, and ABTS radical scavenging ability) induced by the superoxide anion. Finally, we demonstrated that intraplantar injection of potassium superoxide induces the mRNA expression of prepro-endothelin-1 in the paw skin and spinal cord. In conclusion, our results demonstrated that superoxide anion-induced inflammation, pain, cytokine production, and oxidative stress depend on endothelin; therefore, these responses are amenable to bosentan treatment.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Bosentan; Cytokines; Endothelin Receptor Antagonists; Hyperalgesia; Leukocytes; Male; Mice; Pain; Peritoneal Cavity; Peroxidase; Skin; Spinal Cord; Sulfonamides; Superoxides

Inhibition of tumor necrosis factor-alpha (TNFα) and superoxide anion production reduces inflammation and pain. The present study investigated whether superoxide anion-induced pain depends on TNFα signaling and the role of superoxide anion in TNFα-induced hyperalgesia to clarify the interrelation between these two mediators in the context of pain. Intraplantar injection of a superoxide anion donor (potassium superoxide) induced mechanical hyperalgesia (0.5-5h after injection), neutrophil recruitment (myeloperoxidase activity), and overt pain-like behaviors (paw flinching, paw licking, and abdominal writhings) in wild-type mice. Tumor necrosis factor receptor 1 deficiency (TNFR1-/-) and treatment of wild-type mice with etanercept (a soluble TNFR2 receptor that inhibits TNFα actions) inhibited superoxide anion-induced pain-like behaviors. TNFR1(-/-) mice were also protected from superoxide anion donor-induced oxidative stress, suggesting the role of this pathway in the maintenance of oxidative stress. Finally, we demonstrated that Apocynin (an NADPH oxidase inhibitor) or Tempol (a superoxide dismutase mimetic) treatment inhibited TNFα-induced paw mechanical hyperalgesia and neutrophil recruitment (myeloperoxidase activity). These results demonstrate that TNFα/TNFR1 signaling is important in superoxide anion-triggered pain and that TNFα/TNFR1 signaling amplifies the oxidative stress triggered by superoxide anion, which contributes to sustaining pain and inflammation.

Topics: Animals; Anti-Inflammatory Agents; Etanercept; Hyperalgesia; Inflammation; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Neutrophils; Oxidative Stress; Pain; Peroxidase; Physical Stimulation; Receptors, Tumor Necrosis Factor, Type I; Superoxides; Touch; Tumor Necrosis Factor-alpha

To confirm whether class I histone deacetylase inhibitors (HDACIs) are effective in relief of peripheral inflammatory pain, the effects of two selective inhibitors, MS-275 and MGCD0103, were studied in rats inflamed by subcutaneous (s.c.) injection of bee venom (BV). The BV test is characterized by displaying both persistent spontaneous nociception (PSN) and primary hypersensitivity. Intrathecal (i.t.) pre-treatment of either MS-275 or MGCD0103 with a single dose of 60 nmol/20 μL resulted in profound suppression of both PSN and primary thermal hypersensitivity but without significant influence upon the primary mechanical hypersensitivity and mirror-image thermal hypersensitivity. Moreover, the up-regulation of both HDAC1 and HDAC2 induced by s.c. BV injection was completely suppressed by i.t. pre-treatment of MS-275. The present results provide with another new line of evidence showing involvement of epigenetic regulation of chromatin structure by HDAC1/2-mediated histone hypoacetylation in the BV-induced PSN and thermal hypersensitivity and demonstrate the beneficial effects of class I HDACIs in prevention of peripheral inflammatory pain from occurring.

Topics: Animals; Bee Venoms; Benzamides; Epigenesis, Genetic; Histone Deacetylase 1; Histone Deacetylase 2; Histone Deacetylase Inhibitors; Hot Temperature; Hyperalgesia; Inflammation; Injections, Subcutaneous; Nociception; Pain; Pain Measurement; Pyridines; Pyrimidines; Rats; Rats, Sprague-Dawley; Up-Regulation

Nitric oxide is a key signalling molecule in the pathogenesis of inflammation, but its role in acute pancreatitis and related abdominal pain induced by secretory phospholipase A2 (sPLA2 ) from Crotalus durissus terrificus (Cdt) venom has not been investigated.. Male Wistar rats were i.v. injected with L-NAME (20 mg/kg), aminoguanidine (AG, 50 mg/kg), 7-nitroindazole (7-NI, 10 mg/kg) or vehicle 10 min before or 60 min after the injection of sPLA2 (300 μg/kg) into the common bile duct. After 4 h of sPLA2 injection, abdominal hyperalgesia and inflammation were assessed in addition to serum amylase, nitrite/nitrate (NOx), pancreas lipoperoxidation and 3-nitrotyrosine (3-NT) contents.. sPLA2 -induced acute pancreatitis, related abdominal hyperalgesia, hyperamylasemia and increased concentration of NOx were not correlated with lipoperoxidation or increased 3-NT in the pancreas. Pretreatment with all the nitric oxide synthase (NOS) inhibitors significantly reduced abdominal mechanical hyperalgesia, but only iNOS blockade by AG suppressed pancreas oedema and serum NOx increase. The therapeutic approach with all the NOS inhibitors produced a similar reduction pattern of the abdominal hyperalgesia, but AG treatment also inhibited serum hyperamylasemia and NOx concentrations and pancreatic myeloperoxidase. The nNOS blockade by 7-NI treatment also inhibited myeloperoxidase activity in both pancreas and lung.. Therapeutic blockade of iNOS or nNOS provides benefits in terms of inhibition of the acute pancreatitis-related abdominal hyperalgesia, while iNOS inhibition also ameliorates the inflammatory cell influx to the pancreas and reduces the resultant hyperamylasemia and NOx levels, thus representing alternative pharmacological strategies for treatment of clinical pancreatitis associated with increased PLA2 .

Topics: Animals; Enzyme Inhibitors; Hyperalgesia; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; Pain; Pancreas; Pancreatitis; Peroxidase; Phospholipases A2, Secretory; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Tyrosine

The present study aimed to investigate the potential anti-inflammatory and anti-nociceptive effects of carvacryl acetate, a derivative of carvacrol, in mice.. The anti-inflammatory activity was evaluated using various phlogistic agents that induce paw edema, peritonitis model, myeloperoxidase (MPO) activity, pro and anti-inflammatory cytokine levels. Evaluation of antinociceptive activity was conducted through acetic acid-induced writhing, hot plate test, formalin test, capsaicin and glutamate tests, as well as evaluation of motor performance on rotarod test.. Pretreatment of mice with carvacryl acetate (75 mg/kg) significantly reduced carrageenan-induced paw edema (P<0.05) when compared to vehicle-treated group. Likewise, carvacryl acetate (75 mg/kg) strongly inhibited edema induced by histamine, serotonin, prostaglandin E2 and compound 48/80. In the peritonitis model, carvacryl acetate significantly decreased total and differential leukocyte counts, and reduced levels of myeloperoxidase and interleukin-1 beta (IL-1β) in the peritoneal exudate. The levels of IL-10, an anti-inflammatory cytokine, were enhanced by carvacryl acetate. Pretreatment with carvacryl acetate also decreased the number of acetic acid-induced writhing, increased the latency time of the animals on the hot plate and decreased paw licking time in the formalin, capsaicin and glutamate tests. The pretreatment with naloxone did not reverse the carvacryl acetate-mediated nociceptive effect.. In conclusion, the current study demonstrated that carvacryl acetate exhibited anti-inflammatory activity in mice by reducing inflammatory mediators, neutrophil migration and cytokine concentration, and anti-nociceptive activity due to the involvement of capsaicin and glutamate pathways.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Edema; Immune System Diseases; Inflammation; Inflammation Mediators; Leukocyte Disorders; Male; Mice; Monoterpenes; Pain; Peritonitis; Peroxidase

The sulfated polysaccharide (PLS) fraction of Agardhiella ramosissima was characterized by microanalysis, infrared spectroscopy, NMR and gas-liquid-chromatography-mass-spectrometry. The main constituent of PLS was the ι carrageenan. The monosaccharide composition of the PLS showed galactose, 3,6-anhydrogalactose and 6-O-methylgalactose. The PLS (30 mg kg(-1)) significantly reduced the paw oedema induced by carrageenan, dextran, histamine and serotonin and also was able to significantly inhibit leucocyte migration into the peritoneal cavity and decrease the concentration of myeloperoxidase (MPO) in paw tissue. In the antinociceptive tests, the pre-treatment with PLS reduced the number of writhes, the licking time but did not increase the latency time of response. This study demonstrates for the first time the anti-inflammatory and anti-nociceptive effects of PLS from A. ramosissima. Thus, we concluded that PLS could be a new natural tool in pain and acute inflammatory conditions.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cell Movement; Dextrans; Edema; Galactose; Hindlimb; Histamine; Inflammation; Male; Methylgalactosides; Mice; Nociception; Pain; Peroxidase; Plant Extracts; Polysaccharides; Rhodophyta; Serotonin; Spectroscopy, Fourier Transform Infrared

Cyane-carvone (CC) was studied to elucidate its anti-inflammatory, antinociceptive, and antioxidant effects in Mus musculus. Anti-inflammatory (bradykinin, histamine, prostaglandin E2, serotonin, and carrageenan) and antinociceptive (acetic acid and formalin) models were utilized. Myeloperoxidase activity, interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), and glutathione (GSH) levels were evaluated. Analysis of variance followed by Student-Newman-Keuls' test was done. Results were compared with control groups (significantly when p < 0.05). In bradykinin, histamine, prostaglandin E2, and serotonin tests, 75 mg/kg CC decreased significantly paw edema (t = 30, 60, 90, and/or 120 min). In carrageenan test, 50 and 75 mg/kg CC (t = 3 h and t = 4 h) and 25 mg/kg CC (t = 4 h) decreased significantly paw edema. CC (75 mg/kg) inhibited significantly mieloperoxidase activity and decreased IL-1β and TNF-α, and all doses increased GSH levels. CC (75 mg/kg) decreased significantly the number of contortions of animals and time of licking (phase 2). CC showed anti-inflammatory, antinociceptive, and antioxidant effects in mice.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Bradykinin; Carrageenan; Cyclohexane Monoterpenes; Cytokines; Dinoprostone; Edema; Glutathione; Histamine Antagonists; Inflammation; Interleukin-1beta; Male; Mice; Monoterpenes; Oxidative Stress; Pain; Peroxidase; Serotonin Antagonists; Tumor Necrosis Factor-alpha

Marine algae are abundant sources of sulfated polysaccharides with various biological activities. Consequently, their biomolecules are of great of commercial interest. In this study, we investigated the potential antinociceptive activity of a sulfated polysaccharide obtained from the green seaweed Caulerpa racemosa (CrII) and the involvement of the hemoxigenase-1 (HO-1) pathway in its anti-inflammatory effect.. We used a systemic evaluation to verify possible toxic effects of Crll after consecutive treatments. Swiss mice and Wistar rats were used for all experiments.. In Swiss mice, CrII (0.01, 0.1 and 1.0 mg/kg) significantly reduced the number of abdominal contortions and the duration of paw licking in the second phase after treatment with acetic acid and formalin, respectively. However, CrII was unable to prolong the reaction time of thermally stimulated animals. The anti-inflammatory effect of CrII (0.01, 0.1 and 1.0 mg/kg) was evidenced by a decreased number of leukocytes in the peritoneal cavities of the rats. CrII (0.01, 0.1 and 1.0 mg/kg) also reduced the amount of paw edema induced by carrageenan (Cg) and dextran. The anti-inflammatory effect of CrII was confirmed by reduced levels of myeloperoxidase in the paw tissue of the Cg groups. After inhibition with ZnPP IX, a specific HO-1 phenotype inhibitor, the anti-inflammatory effect of CrII was no longer observed in Cg-induced paw edema tests. Consecutive Crll (1.0 mg/kg) for 14 days did not change any biochemical or histopathological parameters, or cause mortality of mice.. CrII did not produce any signs of toxicity and effectively decreased nociception and inflammation. Also, the anti-inflammatory effect of Crll is at least in part dependent on the integrity of the HO-1 pathway.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Caulerpa; Dextrans; Edema; Female; Formaldehyde; Heme Oxygenase (Decyclizing); Hot Temperature; Male; Mice; Pain; Peritonitis; Peroxidase; Phytotherapy; Polysaccharides; Rats, Wistar; Seaweed; Sulfates

Sulphated polysaccharides from marine algae are widely used in biotechnological and pharmaceutical areas. In this study, we evaluated the effects of sulphated polysaccharides from the green marine alga Caulerpa mexicana (Cm-SPs) in nociceptive and inflammatory models in rodents. Cm-SPs (10 or 20 mg/kg), administered i.v. in Swiss mice, significantly reduced nociceptive responses, as measured by the number of writhes in response to acetic acid. Cm-SPs (10 or 20 mg/kg) also reduced second-phase responses in the formalin test, but did not exhibit a significant antinociceptive effect in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. Cm-SPs (5, 10 or 20 mg/kg), administered s.c. in wistar rats 1 hr before carrageenan, dextran, histamine or serotonin, were tested in paw oedema models. Cm-SPs (10 or 20 mg/kg) reduced carrageenan-induced paw oedema and myeloperoxidase activity in the paw. In addition, Cm-SPs (20 mg/kg) inhibited dextran- or histamine-induced paw oedema, but not serotonin-induced oedema, suggesting that histamine is the major target of Cm-SPs anti-oedematogenic activity. Finally, Cm-SPs (20 mg/kg) administered in mice did not show significant signs of toxicity. In conclusion, Cm-SPs appear to be promising natural modulatory agents for pain and inflammatory conditions.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Caulerpa; Dextrans; Disease Models, Animal; Edema; Female; Histamine; Inflammation; Male; Mice; Pain; Pain Measurement; Peroxidase; Polysaccharides; Rats; Rats, Wistar; Serotonin

The fatty acid amide palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory and neuroprotective actions. The lipidic nature and large particle size of PEA in the native state may limit its solubility and bioavailability when given orally, however. Micronized formulations of a drug enhance its rate of dissolution and reduce variability of absorption when orally administered. The present study was thus designed to evaluate the oral anti-inflammatory efficacy of micronized/ultramicronized versus nonmicronized PEA formulations.. Micronized/ultramicronized PEA was produced by the air-jet milling technique, and the various PEA preparations were subjected to physicochemical characterization to determine particle size distribution and purity. Each PEA formulation was then assessed for its anti-inflammatory effects when given orally in the carrageenan-induced rat paw model of inflammation, a well-established paradigm of edema formation and thermal hyperalgesia.. Intraplantar injection of carrageenan into the right hind paw led to a marked accumulation of infiltrating inflammatory cells and increased myeloperoxidase activity. Both parameters were significantly decreased by orally given micronized PEA (PEA-m; 10 mg/kg) or ultramicronized PEA (PEA-um; 10 mg/kg), but not nonmicronized PeaPure (10 mg/kg). Further, carrageenan-induced paw edema and thermal hyperalgesia were markedly and significantly reduced by oral treatment with micronized PEA-m and ultramicronized PEA-um at each time point compared to nonmicronized PeaPure. However, when given by the intraperitoneal route, all PEA formulations proved effective.. These findings illustrate the superior anti-inflammatory action exerted by orally administered, micronized PEA-m and ultramicronized PEA-um, versus that of nonmicronized PeaPure, in the rat paw carrageenan model of inflammatory pain.

Topics: Administration, Oral; Amides; Analgesics; Animals; Carrageenan; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Disease Models, Animal; Edema; Ethanolamines; Hyperalgesia; Inflammation; Male; Microscopy, Electron, Scanning; Pain; Palmitic Acids; Peroxidase; Rats; Rats, Sprague-Dawley

Visceral afferents expressing transient receptor potential (TRP) channels TRPV1 and TRPA1 are thought to be required for neurogenic inflammation and development of inflammatory hyperalgesia. Using a mouse model of chronic pancreatitis (CP) produced by repeated episodes (twice weekly) of caerulein-induced AP (AP), we studied the involvement of these TRP channels in pancreatic inflammation and pain-related behaviors. Antagonists of the two TRP channels were administered at different times to block the neurogenic component of AP. Six bouts of AP (over 3 wks) increased pancreatic inflammation and pain-related behaviors, produced fibrosis and sprouting of pancreatic nerve fibers, and increased TRPV1 and TRPA1 gene transcripts and a nociceptive marker, pERK, in pancreas afferent somata. Treatment with TRP antagonists, when initiated before week 3, decreased pancreatic inflammation and pain-related behaviors and also blocked the development of histopathological changes in the pancreas and upregulation of TRPV1, TRPA1, and pERK in pancreatic afferents. Continued treatment with TRP antagonists blocked the development of CP and pain behaviors even when mice were challenged with seven more weeks of twice weekly caerulein. When started after week 3, however, treatment with TRP antagonists was ineffective in blocking the transition from AP to CP and the emergence of pain behaviors. These results suggest: (1) an important role for neurogenic inflammation in pancreatitis and pain-related behaviors, (2) that there is a transition from AP to CP, after which TRP channel antagonism is ineffective, and thus (3) that early intervention with TRP channel antagonists may attenuate the transition to and development of CP effectively.

Topics: Amidines; Analgesics, Opioid; Analysis of Variance; Animals; Antigens, Differentiation; Calcitonin Gene-Related Peptide; Calcium; Ceruletide; Disease Models, Animal; Disease Progression; Exploratory Behavior; Extracellular Signal-Regulated MAP Kinases; Ganglia, Spinal; Gene Expression Regulation; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Monocytes; Morphine; Neutrophil Infiltration; Nodose Ganglion; Oximes; Pain; Pain Measurement; Pancreas; Pancreatitis, Chronic; Peroxidase; Pyridines; RNA, Messenger; Sensory Receptor Cells; Time Factors; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPV Cation Channels

Valproic acid (VA) is a major antiepileptic drug, used for several therapeutic indications. It has a wide activity spectrum, reflecting on mechanisms of action that are not fully understood. The objectives of this work were to study the effects of VA on acute models of nociception and inflammation in rodents. VA (0.5, 1, 10, 25, and 50 mg/kg, p.o.) effects were evaluated on the carrageenan-induced paw edema, carrageenan-induced peritonitis, and plantar tests in rats, as well as by the formalin test in mice. The HE staining and immunohistochemistry assay for TNF-α in carrageenan-induced edema, from paws of untreated and VA-treated rats, were also carried out. VA decreased paw edema after carrageenan, and maximum effects were seen with doses equal to or higher than 10 mg/kg. VA also preserved the tissue architecture as assessed by the HE staining. Immunohistochemical studies revealed that VA significantly reduced TNF-α immunostaining in carrageenan-inflamed rat paws. In addition, the anti-inflammatory action of VA was potentiated by pentoxifylline (a phosphodiesterase inhibitor, known to inhibit TNF-α production), but not by sodium butyrate or by suberoylanilide hydroxamic acid (SAHA), nonspecific and specific inhibitors, respectively, of histone deacetylase. However, the decrease in the number of positive TNF-α cells in the rat paw was drastically potentiated in the VA + SAHA associated group. VA also reduced leukocytes and myeloperoxidase (MPO) releases to the peritoneal exudate, in the carrageenan-induced peritonitis. Although in the formalin test, VA inhibited both phases, the inhibition was mainly on the second phase. Furthermore, VA significantly increased the reaction time to thermal stimuli, as assessed by the plantar test. VA is a multi-target drug, presenting potent antinociceptive and anti-inflammatory properties at a lower dose range. These effects are partly dependent upon its inhibitory action on TNF-α-related pathways. However, the participation of the HDAC inhibition with the VA anti-inflammatory action cannot be ruled out. Inflammatory processes are associated with free radical damage and oxidative stress, and their blockade by VA could also explain the present results.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Anticonvulsants; Butyric Acid; Carrageenan; Drug Synergism; Edema; Foot; Formaldehyde; Hot Temperature; Hydroxamic Acids; Leukocyte Count; Male; Mice; Pain; Pentoxifylline; Peritonitis; Peroxidase; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Valproic Acid; Vorinostat

Anethole has been reported to have antioxidant, antibacterial, antifungal, antiinflammatory, and anesthetic properties. In the present study, we evaluated the effects of anethole in two pain models of inflammatory origin: acute inflammation induced by carrageenan and persistent inflammation induced by Complete Freund's adjuvant. We evaluated the effects of anethole (125, 250, and 500 mg/kg) on the development of paw oedema and mechanical hypernociception. The liver was collected for histological analysis. Paw skin was collected to determine the levels of the cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-17 (IL-17), and myeloperoxidase activity. Blood was collected to assess alanine transaminase (ALT) and aspartate transaminase (AST). The chemical composition of star anise oil was determined by gas chromatography/mass spectrometry (GC/MS), showing a presence of anethole of 98.1%. Oral pretreatment with anethole in mice inhibited paw oedema, mechanical pernociception, myelopewroxidase activity, TNF-α, IL-1β and IL-17 levels in acute and persistent inflammation models. Additionally, anethole treatment did not alter prostaglandin E2-induced mechanical hypernociception. Possible side effects were also examined. Seven-day anethole treatment did not alter plasma AST and ALT levels, and the histological profile of liver tissue was normal. The present study provides evidence of the antiinflammatory and analgesic activities of anethole in acute and persistent inflammation models.

Topics: Alanine Transaminase; Allylbenzene Derivatives; Analgesics; Animals; Anisoles; Anti-Inflammatory Agents; Aspartate Aminotransferases; Edema; Illicium; Inflammation; Interleukin-17; Interleukin-1beta; Liver; Male; Mice; Neutrophils; Nociception; Oils, Volatile; Pain; Peroxidase; Tumor Necrosis Factor-alpha

Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice.. Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO).. The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls.. Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Blotting, Western; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Diterpenes, Clerodane; Gastrointestinal Motility; Male; Mice; Naltrexone; Pain; Peroxidase; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Opioid, kappa; Salvia; Trinitrobenzenesulfonic Acid

Myrsinoic acid B (MAB) is a diprenylated benzoic acid widely found in the vegetal kingdom. Recent studies demonstrate that MAB has important antinociceptive effects in models of chemically or thermally induced nociception in mice.. In the present study we evaluated the effect of MAB in different models of inflammatory and neuropathic hypersensitivity in mice.. This study demonstrates that the pretreatment with MAB, given orally (8.4 to 83.8 μmol/kg), inhibited carrageenan- and complete Freund adjuvant-induced mechanical hypersensitivity. When administered after the induction of hypersensitivity, MAB also reduced the mechanical hypersensitivity in the ipsilateral and in the contralateral hindpaws of mice injected with complete Freund adjuvant, interfering with a signaling cascade already established. MAB reversed the hypersensitivity (mechanical and thermal) of operated animals, with similar results to those observed with gabapentin. MAB activity was evident when administered either systemically (PO or IV) or intrathecally, suggesting interference in the central pathways of pain control. Furthermore, MAB seems to present an antiinflammatory effect evidenced by the interference in both the neutrophil migration and in the increase of interleukin-1β levels after carrageenan injection. Of note, MAB treatment did not interfere with mechanical or thermal sensitivity in healthy mice, a frequent characteristic of commonly used analgesics, such as morphine or gabapentin. Side effects including interference in locomotor activity, motor performance, and body temperature in animals treated with MAB were absent.. MAB reduced mechanical and thermal hypersensitivity in mice submitted to models of inflammatory and neuropathic pain, showing excellent potential for treating persistent pain in humans.

Topics: Administration, Oral; Alkenes; Analgesics; Animals; Behavior, Animal; Benzofurans; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Freund's Adjuvant; Hyperalgesia; Inflammation; Injections, Intravenous; Interleukin-1beta; Mice; Motor Activity; Neuralgia; Neutrophil Infiltration; Pain; Pain Measurement; Pain Threshold; Peroxidase; Time Factors

This study investigated the antinociceptive effect of Aleurites moluccana dried extract (DE; 125 to 500 mg/kg, p.o.) and the isolated flavonoid 2″-O-rhamnosylswertisin (5 to 50.6 μmol/kg, p.o.) using different models of long-lasting inflammatory and neuropathic pain in mice. Attempts were made to analyse the mechanisms through which A. moluccana exerted its effects. A. moluccana DE inhibited complete Freund's adjuvant (CFA)-induced mechanical nociception. It was also evidenced by a reduction of sensitization in the contralateral hindpaw. The extract reversed the mechanical hypersensitivity of partial ligation of sciatic nerve (PLSN)-treated animals, similar to gabapentin. In PLSN model, the opioid, dopaminergic and oxidonitrergic pathways were involved in the A. moluccana DE antinociceptive effects. A single dose of 2″-O-rhamnosylswertisin inhibited the carrageenan- and CFA-induced mechanical nociception. Furthermore, the compound caused expressive antinociception in PLSN-mice, with inhibition value greater than obtained with gabapentin. Oral treatment with the extract or the isolated compound attenuated the neutrophil migration and IL-1β levels following carrageenan injection. Of note, A. moluccana DE did not interfere with thermal sensitivity in healthy mice. The absence of side effects, including interference in locomotor activity, motor performance in animals treated with the extract, showed excellent potential for the therapeutic use of this medicinal plant in treating persistent pain in humans.

Topics: Aleurites; Analgesics; Animals; Female; Flavones; Interleukin-1beta; Mice; Mice, Inbred C57BL; Pain; Peroxidase; Rhamnose

D-002, a mixture of six higher aliphatic alcohols purified from beeswax, displayed anti-inflammatory effects in carrageenan-induced pleurisy and cotton pellet granuloma in rats. The aim of the present study was to confirm the anti-inflammatory properties of D-002 and to explore its potential analgesic effects. Xylene-induced mouse ear oedema was used to assess the anti-inflammatory effect, acetic acid-induced writhing and hot plate responses for the analgesic activity, and the open field and horizontal rotarod tests for motor performance. For anti-inflammatory tests, mice were randomised into a negative vehicle control and five xylene-treated groups: the vehicle, D-002 (25, 50 and 200 mg/kg) and indomethacin 1 mg/kg (reference drug). Treatments were given for 15 days. Effects on oedema formation and myeloperoxidase (MPO) activity were tested. For analgesia and motor performance tests, mice were randomised into a vehicle control and D-002-treated groups (25, 50 and 200 mg/kg). Two sets of experiments were done, which included acute and repeat (15 days) dosing. D-002 (25, 50 and 200 mg/kg) significantly decreased xylene-induced ear oedema (44.7, 60.8 and 76.4%, respectively) and the increase of MPO activity induced by xylene (38.0, 47.0 and 57.0%, respectively), while indomethacin significantly inhibited xylene-induced oedema (59.9%) and MPO activity (57.5%). Single and repeat doses of D-002 (25, 50 and 200 mg/kg) decreased the acetic acid-induced writhing responses by 21.2, 28.2 and 40.1%, for the single doses; 25.2, 35.1 and 43.2%, respectively, for the repeat doses, but did not affect the hot plate, open field and rotarod behaviours. Aspirin 100 mg/kg significantly decreased acetic acid-induced abdominal constrictions and morphine (5 mg/kg) significantly increased the latency of the hot plate response. This study confirmed the anti-inflammatory effects of D-002 and demonstrated its analgesic effects on the acetic acid-induced writhing, but not on the hot plate response, which suggests that the antinociceptive effects of D-002 could be related to its anti-inflammatory activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Edema; Fatty Alcohols; Male; Mice; Pain; Peroxidase; Random Allocation

Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay.. In the formalin test although Mino and Dox (1, 5, 10 and 25 mg/kg, i.p.) inhibited the first phase, they acted predominantly on the second phase of the test, where inhibition of the licking time close to 80% were observed. Mino and Dox were very efficacious in reducing the carrageenan-induced paw oedema in rats (10, 25 and 50 mg/kg, i.p.) and carrageenan-induced leucocyte migration (1 and 5 mg/kg, i.p.) to mice peritoneal cavities. Besides, they also significantly inhibited MPO and LDH releases at doses ranging from 0.001 to 1 μg/ml. Thus, in general, the anti-inflammatory activity of Dox was higher as compared to that of Mino, although the radical scavenging activity of Mino was of a magnitude 10 times higher.. Our data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.

Topics: alpha-Tocopherol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biphenyl Compounds; Carrageenan; Cell Movement; Doxycycline; Edema; Formaldehyde; Inflammation; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred Strains; Minocycline; Neutrophils; Nitric Oxide Synthase Type II; Oxidation-Reduction; Pain; Pain Measurement; Peritonitis; Peroxidase; Picrates; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The present study was designed to evaluate the antinociceptive profile of caffeic acid in mice and rats. Caffeic acid (5-100 mg/kg, p.o.), in a dose dependent manner inhibited acetic acid-induced writhing and late phase of formalin-induced pain in mice, with an ED(50) of 22.38 and 10.92 mg/kg, respectively. However, caffeic acid was ineffective in the hot plate and tail flick tests. Analgesic activity was also examined in carrageenan and lipopolysaccharide (LPS)-induced mechanical hyperalgesia in rats, where locally induced myeloperoxidase (MPO), malondialdehyde (MDA) and nitrite levels in foot pad were estimated by colorimetric assay. Oral administration of caffeic acid (200mg/kg, p.o.) showed analgesic activity similar to nimesulide (4 mg/kg, p.o.) and inhibited MPO, MDA and nitrite generation in the inflamed paw. Histological examination revealed reduction in neutrophil infiltration and protection of tissue damage by caffeic acid. These results suggest that caffeic acid exhibits peripheral analgesic effect in mice and rats and could be further examined for the treatment of chronic painful episodes.

Topics: Acetates; Animals; Behavior, Animal; Caffeic Acids; Carrageenan; Formaldehyde; Inflammation; Lipopolysaccharides; Male; Malondialdehyde; Mice; Nitrites; Pain; Peroxidase; Rats

We report herein a case of microscopic polyangiitis (MPA), presenting onset with a spiking fever, liver/biliary dysfunction without jaundice and calf pain without elevation of serum creatine phosphokinase. During 1 month of careful examinations for initial diagnosis, the patient developed renal dysfunction and pulmonary hemorrhage. Based on the results of positive MPO-ANCA, renal and pulmonary involvements, the patient was diagnosed with MPA and treated with high-dose prednisolone and oral cyclophosphamide. Soon after initiation of the treatment, symptoms such as fever, calf pain, liver/biliary dysfunction and renal dysfunction disappeared with decrease of MPO-ANCA titer to the normal level.

Topics: Administration, Oral; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Dose-Response Relationship, Drug; Female; Fever of Unknown Origin; Humans; Leg; Liver Diseases; Microscopic Polyangiitis; Middle Aged; Pain; Peroxidase; Prednisolone; Treatment Outcome

Cot/tpl2 (also known as MAP3K8) has emerged as a new and potentially interesting therapeutic anti-inflammatory target. Here, we report the first study of Cot/tpl2 involvement in acute peripheral inflammation in vivo. Six hours after an intraplantar injection of zymosan, Cot/tpl2(-/-) mice showed a 47% reduction in myeloperoxidase activity, concomitant with a 46% lower neutrophil recruitment and a 40% decreased luminol-mediated bioluminescence imaging in vivo. Accordingly, Cot/tpl2 deficiency provoked a 25-30% reduction in luminol-mediated bioluminescence and neutrophil recruitment together with a 65% lower macrophage recruitment 4 h following zymosan-induced peritonitis. Significantly impaired levels of G-CSF and GM-CSF and of other cytokines such as TNFα, IL-1β, and IL-6, as well as some chemokines such as MCP-1, MIP-1β, and keratinocyte-derived chemokine, were detected during the acute zymosan-induced intraplantar inflammatory response in Cot/tpl2(-/-) mice. Moreover, Cot/tpl2 deficiency dramatically decreased the production of the hypernociceptive ligand NGF at the inflammatory site during the course of inflammation. Most importantly, Cot/tpl2 deficiency significantly reduced zymosan-induced inflammatory hypernociception in mice, with a most pronounced effect of a 50% decrease compared with wild type (WT) at 24 h following intraplantar injection of zymosan. At this time, Cot/tpl2(-/-) mice showed significantly reduced NGF, TNFα, and prostaglandin E(2) levels compared with WT littermates. In conclusion, our study demonstrates an important role of Cot/tpl2 in the NGF, G-CSF, and GM-CSF production and myeloperoxidase activity in the acute inflammatory response process and its implication in inflammatory hypernociception.

Topics: Animals; Chemokines; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Inflammation; Interleukin-1beta; Interleukin-6; Male; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pain; Peroxidase; Proto-Oncogene Proteins; Tumor Necrosis Factor-alpha

Post-inflammatory pain is a poorly understood phenomenon. G protein-coupled receptors are involved in regulating pain signaling in the context of inflammation. G protein-coupled receptor kinases (GRK) modulate signaling through these receptors. We investigated whether GRK6 contributes to post-inflammatory visceral hyperalgesia. Colitis was induced in female mice by 1% dextran sodium sulphate in drinking water for 7 days. Disease score, colon length, and colonic cytokines were determined. On day 49, when animals had recovered from colitis, we induced visceral pain by intracolonic capsaicin instillation. Behavioral responses to capsaicin were monitored for 20 min. Referred hyperalgesia was measured using von Frey hairs. Spinal cord c-Fos was visualized by immunohistochemistry. In contrast to our earlier observations in male GRK6-/- and wild type (WT) mice, we did not detect differences in the course of colitis or in expression of colonic cytokines between female GRK6-/- and WT mice. After recovery from colitis, capsaicin-induced behavioral pain responses and spinal cord c-Fos expression were more pronounced in female GRK6-/- than WT mice. Naive GRK6-/- and WT animals did not differ in pain and c-Fos responses to capsaicin. Capsaicin-induced referred hyperalgesia post-colitis was increased in GRK6-/- compared to WT mice. However, referred hyperalgesia post-colitis was not affected by ablation of GRK6. Furthermore, in vitro IL-1beta sensitized the capsaicin receptor TRPV1 and this process was inhibited by over-expression of GRK6. We describe the novel concept that GRK6 inhibits post-inflammatory visceral hyperalgesia but does not contribute to visceral pain in naive animals. We propose that GRK6 regulates inflammation-induced sensitization of TRPV1.

Topics: Analysis of Variance; Animals; Blotting, Western; Capsaicin; Cell Line; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Female; G-Protein-Coupled Receptor Kinases; Hyperalgesia; Inflammation; Mice; Mice, Inbred C57BL; Pain; Pain Measurement; Pain Threshold; Peroxidase; Proto-Oncogene Proteins c-fos; Visceral Afferents

Temporomandibular disorders represent one of the major challenges in dentistry therapeutics. This study was undertaken to evaluate the time course of carrageenan-induced inflammation in the rat temporomandibular joint (TMJ) and to investigate the role of tachykinin NK(1) receptors. Inflammation was induced by a single intra-articular (i.art.) injection of carrageenan into the left TMJ (control group received sterile saline). Inflammatory parameters such as plasma extravasation, leukocyte influx and mechanical allodynia (measured as the head-withdrawal force threshold) and TNFalpha and IL-1beta concentrations were measured in the TMJ lavages at selected time-points. The carrageenan-induced responses were also evaluated after treatment with the NK(1) receptor antagonist SR140333. The i.art. injection of carrageenan into the TMJ caused a time-dependent plasma extravasation associated with mechanical allodynia, and a marked neutrophil accumulation between 4 and 24h. Treatment with SR140333 substantially inhibited the increase in plasma extravasation and leukocyte influx at 4 and 24h, as well as the production of TNFalpha and IL-1beta into the joint cavity, but failed to affect changes in head-withdrawal threshold. The results obtained from the present TMJ-arthritis model provide, for the first time, information regarding the time course of this experimental inflammatory process. In addition, our data show that peripheral NK(1) receptors mediate the production of both TNFalpha and IL-1beta in the TMJ as well as some of the inflammatory signs, such as plasma extravasation and leukocyte influx, but not the nociceptive component.

Topics: Animals; Carrageenan; Data Interpretation, Statistical; Extravasation of Diagnostic and Therapeutic Materials; Inflammation; Interleukin-1beta; Leukocyte Count; Male; Neurokinin-1 Receptor Antagonists; Pain; Peroxidase; Piperidines; Quinuclidines; Radiopharmaceuticals; Rats; Rats, Wistar; Receptors, Neurokinin-1; Serum Albumin, Radio-Iodinated; Substance P; Temporomandibular Joint Disorders; Tumor Necrosis Factor-alpha

To examine a possible involvement of reactive oxygen species (ROS) in visceral pain, the levels of ROS in the colon and the effect of a ROS scavenger phenyl N-t-butylnitrone (PBN) on pain were examined in zymosan-induced colitis rats. Zymosan was instilled into the colon of adult rats. The electromyograms (EMGs) of abdominal muscle contractions in response to colorectal distension (CRD) were recorded as an indicator of visceral pain. After zymosan treatment, the rats showed enhanced EMG and elevated levels of H2O2 in the colon. PBN treatment (intraperitoneal, intrathecal or intracolonic) significantly reduced the enhanced EMGs induced by zymosan. The results suggest that elevated ROS in the spinal cord and the colon are involved in visceral pain.

Topics: Analysis of Variance; Animals; Cyclic N-Oxides; Dose-Response Relationship, Drug; Drug Interactions; Electromyography; Hydrogen Peroxide; Male; Neuroprotective Agents; Pain; Pain Measurement; Pain Threshold; Peroxidase; Rats; Rats, Sprague-Dawley; Time Factors; Zymosan

In this study, we tested the potential use of a lectin from Lonchocarpus sericeus seeds (LSL), to control neutrophil migration and inflammatory hypernociception (decrease of nociceptive threshold). Pretreatment of the animals intravenously (15 min before) with LSL inhibited neutrophil migration to the peritoneal cavity in a dose-dependent fashion confirmed by an inhibition of rolling and adhesion of leukocytes by intravital microscopy. We also tested the ability of the pretreatment with LSL to inhibit neutrophil migration on immunised mice, and it was observed that a strong inhibition of neutrophil migration induced by ovoalbumin in immunized mice. Another set of experiments showed that pretreatment of the animals with LSL, inhibited the mechanical hypernociception in mice induced by the i.pl. injection of OVA in immunized mice and of carrageenan in naïve mice, but not that induced by prostaglandin E(2) (PGE(2)) or formalin. This anti-nociceptive effect correlated with an effective blockade of neutrophil influx, as assessed by the hind paw tissue myeloperoxidase levels. In addition, we measured cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1alpha [CCL3] and KC [CXCL1]) from the peritoneal exudates and i.pl. tissue. Animals treated with LSL showed inhibition of cytokines and chemokines release in a dose-dependent manner. In conclusion, we demonstrated that the inhibitory effects of LSL on neutrophil migration and mechanical inflammatory hypernocicepetion are associated with the inhibition of the production of cytokines and chemokines.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Cell Adhesion; Cell Movement; Cytokines; Dinoprostone; Fabaceae; Formaldehyde; Immunoglobulin G; Male; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; Pain; Peroxidase; Plant Lectins

The present study examined the anti-hypernociceptive effects of agmatine (AGM) in acute and chronic models of behavioural pain in mice. Agmatine (30 mg/kg, i.p. 30 min early), produced time-dependent inhibition of mechanical hypernociception induced by Complete Freund's Adjuvant (CFA) injected in the mice paw (inhibition of 52+/-7%) after 4 h. Given chronically (twice a day) during 10 days, AGM significantly reversed the mechanical hypernociception caused by CFA (inhibition of 43+/-6% to 67+/-5%). Moreover, AGM also significantly reduced the mechanical hypernociception caused by partial sciatic nerve ligation (PSNL) during 6 h, with inhibition of 81+/-8%. In thermal hypernociception (cold stimuli) caused by PSNL the antinociceptive effect of AGM was prolonged by 4 h with inhibition of 97+/-3% observed 1 h after the treatment. Nevertheless, AGM failed to inhibit the paw oedema caused by CFA and the myeloperoxidase enzyme activity. Of note, AGM (10-100 mg/kg, i.p., 30 min before) also elicited a pronounced inhibition of the biting response induced by TNF-alpha and IL-1beta in mice, with mean ID(50) values of 61.3 mg/kg (47.7-78.6 mg/kg) and 30.4 mg/kg (18.6-49.8 mg/kg) and inhibitions of 75+/-5% and 66+/-6%, respectively. Together, present and previous findings show that AGM given systemically is effective in inhibiting mechanical and thermal hypernociception present in chronic inflammatory processes caused by CFA and also the neuropathic pain caused by PSNL.

Topics: Agmatine; Analgesics; Analysis of Variance; Animals; Behavior, Animal; Cytokines; Disease Models, Animal; Edema; Female; Freund's Adjuvant; Inflammation; Mice; Neutrophils; Pain; Pain Measurement; Peroxidase; Sciatic Neuropathy

1. The present study evaluated the participation of tumour necrosis factor-alpha (TNF-alpha) in the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw. 2. The intraplantar injection of carrageenan (300 microg paw-1) induced a marked and biphasic paw oedema formation (peaks at 6 and 72 h), which was accompanied by a long-lasting mechanical allodynia (that remained elevated for up to 72 h) and a significant increase of myeloperoxidase (MPO) activity (peak at 6 h) in both Swiss and C57/BL6 mice. 3. The paw oedema, the elevation of MPO activity and to a lesser extent the mechanical allodynia elicited by carrageenan were found to be significantly reduced in TNF-alpha p55 receptor knockout mice. 4. Of interest, the systemic administration of an anti-TNF-alpha antibody produced a significant inhibition of paw oedema, mechanical allodynia and MPO activity. A noteworthy decrease in inflammatory and nociceptive responses caused by carrageenan was also observed when mice were previously treated with the preferential inhibitor of TNF-alpha synthesis, thalidomide. 5. The present results clearly indicate that the proinflammatory cytokine TNF-alpha plays a critical role in the oedema formation, as well as in the mechanical allodynia and the neutrophil migration, following carrageenan administration into the mouse paw. Intraplantar injection of carrageenan in mice could constitute a useful model for assessment of the in vivo effects of potential inhibitors of TNF-alpha-related pathways.

Topics: Animals; Carrageenan; Edema; Foot; Foot Diseases; Foot Injuries; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pain; Pain Measurement; Peroxidase; Tumor Necrosis Factor-alpha

There is evidence that sensitization of neurons in dorsal root ganglia (DRG) may contribute to pain induced by intestinal injury. We hypothesized that obstruction-induced pain is related to changes in DRG neurons and satellite glial cells (SGCs). In this study, partial colonic obstruction was induced by ligation. The neurons projecting to the colon were traced by an injection of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate into the colon wall. The electrophysiological properties of DRG neurons were determined using intracellular electrodes. Dye coupling was examined with an intracellular injection of Lucifer yellow (LY). Morphological changes in the colon and DRG were examined. Pain was assessed with von Frey hairs. Partial colonic obstruction caused the following changes. First, coupling between SGCs enveloping different neurons increased 18-fold when LY was injected into SGCs near neurons projecting to the colon. Second, neurons were not coupled to other neurons or SGCs. Third, the firing threshold of neurons projecting to the colon decreased by more than 40% (P < 0.01), and the resting potential was more positive by 4-6 mV (P < 0.05). Finally, the number of neurons displaying spontaneous spikes increased eightfold, and the number of neurons with subthreshold voltage oscillations increased over threefold. These changes are consistent with augmented neuronal excitability. The pain threshold to abdominal stimulation decreased by 70.2%. Inflammatory responses were found in the colon wall. We conclude that obstruction increased neuronal excitability, which is likely to be a major factor in the pain behavior observed. The augmented dye coupling between glial cells may contribute to the neuronal hyperexcitability.

Topics: Action Potentials; Animals; Axotomy; Behavior, Animal; Cell Size; Colonic Diseases; Electrophysiology; Female; Ganglia, Spinal; Gap Junctions; Intestinal Obstruction; Male; Membrane Potentials; Mice; Mice, Inbred BALB C; Pain; Pain Measurement; Pain Threshold; Peroxidase; Satellite Cells, Perineuronal

The leaves of Pimenta racemosa var. ozua (Urban & Ekman) Landrum L. (Myrtaceae) are used against the pain and the inflammation in popular medicine of the Caribe area. In the present work, the antinociceptive, anti-inflammatory effect, and acute toxicity of the aqueous extract from leaves of Pimenta racemosa have been investigated. The antinociceptive action was assayed in several experimental models in mice: acetic acid, formalin, and hot plate tests. The aqueous extract (125 and 250 mg/kg) significantly and in a dose-dependent manner reduced the nociception induced by the acetic acid intraperitoneal injection (P<0.001). In the formalin test, the extract also significantly reduced the painful stimulus in both phases of the test (P<0.001). On the contrary, the extract neither significantly increased the latency time of licking nor jumping in the hot plate test. In the anti-inflammatory study, the plant also showed an interesting effect. Aqueous extract (125 and 250 mg/kg) orally administered, significantly reduced the carrageenan-induced edema in rat paw at 1, 3, and 5 h (P<0.001). In the TPA test the edema was dose-dependent and significantly reduced by the extract (0.5, 1, and 3 mg per ear) when it was topically applied (P<0.01; P<0.001). The levels of myeloperoxidase enzyme also were reduced in the inflamed tissue by the extract. Acute toxicity also was investigated and the results indicated a moderate toxicity (LD50: 287 +/- 12.9 mg residue/kg; 1.854 +/- 0.083 g plant/kg). These results revealed that the extract from leaves of Pimenta racemosa var. ozua exerts an important antinociceptive activity, associated to an anti-inflammatory effect which to appear be markedly influenced by the inhibition of neutrophil migration into inflamed tissue and that lack of toxic effects at usual doses.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Inflammation; Male; Mice; Pain; Peroxidase; Phytotherapy; Pimenta; Plant Leaves; Rats; Rats, Wistar

This study investigated the anti-allodynic and anti-oedematogenic effects of the hexanic extract, lignan-rich fraction and purified lignans from a plant used in the traditional medicine, Phyllanthus amarus, in the inflammatory and neuropathic models of nociception. The hexanic extract inhibited the allodynia and the oedema induced by the intraplantar injection of complete Freund's adjuvant (CFA). The inhibition observed was 76 +/- 7% (ipsilateral paw), 64 +/- 7% (contralateral paw), and 41 +/- 2% (oedema). Otherwise, the lignan-rich fraction or the pure lignans did not affect CFA-induced allodynia. Administered chronically, the lignan fraction reduced CFA-induced paw oedema (39 +/- 9%). When evaluated in the model of neuropathic pain caused by partial ligation of sciatic nerve, the hexanic extract inhibited the mechanical allodynia (77 +/- 7%), with a similar efficacy to the gabapentin (71 +/- 10%). The anti-allodynic effects of hexanic extract of P. amarus seem not to be associated with the impairment of motor co-ordination or with the development of tolerance. Finally, the treatment with hexanic extract inhibited the increase of myeloperoxidase activity, either following intraplantar injection of CFA or after sciatic nerve injury. It is concluded that, apart from its anti-inflammatory actions, which are probably linked to the presence of lignans, another as yet unidentified active principle(s) present in the hexanic extract of P. amarus produces pronounced anti-allodynia in two models of inflammatory and neuropathic pain. Considering that few drugs are currently available for the treatment of chronic pain, especially of the neuropathic type, the present results may have clinical relevance and open new possibilities for the development of new anti-allodynic drugs.

Topics: Acetates; Amines; Analgesics; Animals; Anti-Inflammatory Agents; Cyclohexanecarboxylic Acids; Edema; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Freund's Adjuvant; Gabapentin; gamma-Aminobutyric Acid; Hexanes; Inflammation; Ligation; Lignans; Male; Mice; Motor Activity; Neutrophil Infiltration; Pain; Peripheral Nervous System Diseases; Peroxidase; Phyllanthus; Physical Stimulation; Plant Extracts; Psychomotor Performance; Sciatica; Solvents

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility. There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS, which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided.. Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats. The extent of inflammation was assessed by histological examination and myeloperoxidase (MPO) activity assay. After subsidence of colitis, the rats were subjected to rectal distension and restraint stress, then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively.. At 2 days post-induction of colitis, the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity. At 7 days post-induction of colitis, the histological features and MPO activity returned to normal. The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompanying change in rectal compliance, and defecated more stools than control animals when under stress.. These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.

Topics: Acetic Acid; Animals; Biomarkers; Colitis; Disease Models, Animal; Inflammation; Irritable Bowel Syndrome; Male; Pain; Peroxidase; Rats; Rats, Sprague-Dawley

In human, digestive disorders are often associated with visceral pain. In these pathologies, visceral pain threshold is decreased indicating a visceral hypersensitivity. Pregabalin [CI-1008; S-(+)-3-isobutylgaba] presents antihyperalgesic actions in inflammatory somatic pain models. This study was designed to evaluate 1) the effect of injection of TNBS into the colon on visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS-induced chronic colonic allodynia. A significant decrease in the colonic pain threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals (17.8 +/- 1.27 versus 43.4 +/- 1.98 mm Hg). Pregabalin (30-200 mg/kg s.c.) and morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.) significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS-induced colonic allodynia but did not modify the colonic threshold in normal conditions. The ability of pregabalin to block the chronic colonic allodynia indicates that it is effective in abnormal colonic hypersensitivity, suggesting a possible effect in chronic pain in irritable bowel syndrome.

Topics: Analgesics, Opioid; Animals; Chronic Disease; Colon; Colonic Diseases; gamma-Aminobutyric Acid; Hyperemia; Male; Morphine; Organ Size; Pain; Peroxidase; Pregabalin; Rats; Rats, Sprague-Dawley; Time Factors; Trinitrobenzenesulfonic Acid

Extracts obtained from aerial parts of Stachys inflata have been used in Iranian folk medicine in infective, rheumatic and other inflammatory disorders. In the present study, the anti-inflammatory properties of total methanol extract isolated from aerial parts of Stachys inflata were investigated in two well-characterised inflammatory models in rats, carrageenan-induced paw oedema and formalin-induced paw licking. Intraperitoneal injection of the extract, 60 min before induction of inflammation, revealed a dose-related inhibition of carrageenan-induced rat paw oedema over the dose range 50-200 mg/kg. In the formalin test, the extract (50, 100 and 200 mg/kg) had no effect against the first phase (0-5 min) of the formalin-induced pain, but all three doses produced a significant blockade of the second phase (P < 0.001). Myeloperoxidase (MPO) activity was determined, and a histopathological study was carried out in paw tissue 4 h after induction of inflammation. The hydroalcoholic extract (200 mg/kg) substantially reduced MPO activity (P < 0.05), which was increased in the control group. Histological examination showed a marked reduction in tissue injury and inhibition in neutrophil infiltration in rats treated with the extract (200 mg/kg).

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Dose-Response Relationship, Drug; Edema; Formaldehyde; Lamiaceae; Male; Methanol; Pain; Peroxidase; Plant Extracts; Rats; Rats, Wistar

The leukotrienes are potent inflammatory mediators, which may have a role in inflammatory diseases such as allergic rhinitis, inflammatory bowl disease and asthma. Zafirlukast, a cysteinyl leukotriene receptor antagonist, is claimed to be effective in asthma. However, it is not known whether these leukotrienes are involved in nociceptive and peripheral inflammation. The present study aimed to assess the role of cysteinyl leukotrienes in nociceptive and inflammatory conditions in experimental animals. Central nociception was assessed with tail-flick and hot-plate methods and peripheral nociception was assessed by acetic acid-induced chemonociception in mice. Local administration (intraplantar) of carrageenan-induced hyperalgesia and inflammation, measured by paw withdrawal latency and paw volumes, respectively. Zafirlukast (2.5--20 mg/kg, p.o.) produced a significant and dose-dependent antinociceptive and antiinflammatory effect against acetic acid-induced chemonociception in mice and carrageenan-induced paw oedema in rats, respectively. Zafirlukast (2.5 and 5.0 mg/kg, p.o.) also attenuated the carrageenan-provoked hyperalgesia but did not alter the pain threshold in central nociception up to 20 mg/kg. Zafirlukast (5 and 10 mg/kg ) significantly inhibited exudate formation and migration of polymorphonuclear leukocytes in carrageenan-induced pleurisy. Further, zafirlukast (5 mg/kg) also reduced myeloperoxidase activity in carrageenan-treated paw. When nimesulide (2 mg/kg, p.o.) was co-administered with zafirlukast, the antinociceptive, antihyperalgesic and antiinflammatory effects of nimesulide were significantly increased as compared to the per se effect. The results indicate that cysteinyl leukotrienes are involved in nociceptive/inflammatory conditions. It is expected that combination of cysteinyl leukotriene receptor antagonist with cyclooxygenase inhibitor would prove to be a novel approach to treat complex inflammatory conditions.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Cell Migration Inhibition; Cell Movement; Cysteine; Dose-Response Relationship, Drug; Drug Synergism; Female; Indoles; Inflammation; Leukocytes; Leukotriene Antagonists; Leukotrienes; Male; Mice; Nociceptors; Pain; Pain Measurement; Peroxidase; Phenylcarbamates; Rats; Rats, Wistar; Sulfonamides; Time Factors; Tosyl Compounds

A-57-year-old woman had suffered from high fever, general malaise, and loss of weight (6 kg) since January, 2000. She was admitted to our hospital in May, 2000, because of gait disturbance following to swelling of bilateral calves with severe pain beside the above symptoms. Laboratory data showed leukocytosis (WBC 10,000/microliter), high ESR (98 mm/hr), positive CRP (3.43 mg/dl), positive ANA (x160), high titer of RA (266 IU/l), and a low titer of MPO-ANCA (18 EU). T 2-weighted magnetic resonance image (MRI) showed intensity area of the M. gastrocnemius. Skin biopsy specimens of the right leg demonstrated necrotizing arteritis of small-sized arteries. These findings supported the diagnosis of limited type of polyarteritis nodosa (PN). In this report, we demonstrate a rare case of PN limited to both calves with characteristic MRI findings and a low titer of MPO-ANCA.

Topics: Antibodies, Antineutrophil Cytoplasmic; Female; Humans; Leg; Middle Aged; Pain; Peroxidase; Polyarteritis Nodosa

Loose ligation of a rat sciatic nerve (chronic constriction injury (CCI) model) provokes signs and symptoms like those observed in reflex sympathetic dystrophy (RSD) patients. Primary afferent nociceptive C-fibers seem to be involved in an afferent orthodromic as well as in an efferent antidromic manner. In this study we hypothesize that consequent to development of antidromic impulses in C-nociceptive afferents, neuropeptides released from peripheral endings of these fibers, increase skin blood flow (SBF), vascular permeability, and tissue accumulation of polymorphonuclear leukocytes (PMNs). Collectively, these phenomena have been referred to as neurogenic inflammation. To investigate the presence of neurogenic inflammation in the CCI-model, we assessed skin blood flow (SBF) as well as the level of edema and accumulation of PMNs in muscle tissue obtained from the affected hindpaw. SBF was measured, by means of laser Doppler flowmetry, before ligation as well as at day 4 after ligation. At day 4, SBF measurements were performed before and after abolition of the capability of C-fibers to mediate a vasodilator response. To this end, capsaicin was applied perineurally. Increased vascular permeability was inferred from the level of edema of muscle tissue as determined by assessment of wet/dry weight ratios of muscle biopsies. PMN accumulation was investigated by enzymatic detection of myeloperoxidase (MPO) activity in muscle biopsies. Compared with preligation values, at day 4 SBF was increased more than twofold (p < 0.05). The latter response was annihilated by capsaicin application. Compared with sham operated controls, wet/dry ratios were higher in the ligated animals (1.104 vs. 1.068; p < 0.05). Likewise, when compared with sham operated controls, MPO activity was found to be increased in the ligated hindpaw (Optic Density 0.15 vs. 0.89; p < 0.001). In conclusion, the findings of this study indicate that loose ligation of a sciatic nerve induces an inflammatory response in the ipsilateral hindpaw, which most likely is mediated by release of neuropeptides from the peripheral endings of antidromically acting nociceptive C-fibres.

Topics: Animals; Disease Models, Animal; Edema; Laser-Doppler Flowmetry; Ligation; Male; Muscle, Skeletal; Neuritis; Neutrophils; Nociceptors; Organ Size; Pain; Peroxidase; Rats; Rats, Inbred Lew; Reflex Sympathetic Dystrophy; Sciatic Nerve; Skin