A-80426 suppresses CFA-induced inflammatory pain by suppressing TRPV1 activity via NFκB and PI3K pathways in mice

Abstract Objectives Pain is associated with many circumstances, including inflammatory reactions, which arise from modification of the features of signaling pathways. α2-adrenergic receptor antagonists are widely utilized in narcosis. Here, the authors focused on the narcotic effect of A-80426 (A8) on Complete Freund's Adjuvant (CFA) injections-triggered chronic inflammation pain in WT and TRPV1-/- mice and explored whether its antinociceptive impact was modulated via Transient Receptor Potential Vanilloid 1 (TRPV1). Method CFA with or without A8 was co-administered to the mice, which were categorized randomly into four groups: CFA, A8, control, and vehicle. Pain behaviors underwent evaluation through mechanical withdrawal threshold, abdominal withdrawal reflex, and thermal withdrawal latency of WT animals. Results Quantitative polymerase chain reaction revealed that inflammation-promoting cytokines (IL-1β, IL-6, and TNF-α) were upregulated in Dorsal Root Ganglion (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT animals. A8 administration reduced the pain behaviors and production of pro-inflammatory cytokines; however, this effect was significantly reduced in TRPV1-/- mice. Further analysis showed that CFA treatment reduced the TRPV1 expression in WT mice and A8 administration increased its expression and activity. The co-administration of SB-705498, a TRPV1 blocker, did not influence the pain behaviors and inflammation cytokines in CFA WT mice; however, SB-705498 the effect of A8 in WT mice. In addition, the TRPV1 block decreased the NFκB and PI3K activation in the Dorsal Root Ganglia (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT mice. Conclusions Together, A8 exerted a narcotic impact on CFA-supplemented mice via the TRPV1-modulated NFκB and PI3K pathway.

Therapeutic effects of Durian wood bark extract on a rat model of rheumatoid arthritis / Los efectos terapéuticos del extracto de corteza de madera durián en un modelo de rata de artritis reumatoide

ABSTRACT Background: Rheumatoid arthritis (RA) is a common immune-mediated inflammatory disease characterized by increased inflammation of synovial joint, and often associated with disability. Although several studies have demonstrated the medicinal properties of durian, little is known about the role of durian wood bark for medicinal purposes. Thus, this study investigated the anti-arthritic activity of durian wood bark extract in a rat model of rheumatoid arthritis. Methods: The rats were divided into five groups, including control, RA model, and RA model treated with durian wood bark extract (20, 30, and 40 mg/kg/day for 14 days). The effects of treatment were evaluated by clinical, as well as histological changes in the ankle joints, and the expression level of inducible nitric oxide synthase (iNOS). Results: A complete Freund's adjuvant (CFA)-induced RA model in rats was successfully, characterized by the swelling of hind limbs, histopathological changes in ankle joints, and the upregulation of iNOS expression. The administration of durian wood bark extract at a dose of 40 mg/kg attenuated all parameters analyzed in CFA-induced RA model in rats. Conclusion: Amelioration of hind limb swelling, histopathological changes, and iNOS expression in the RA model indicates that durian wood bark extract can be considered as a new treatment alternative that reduces joint symptoms, as well as a future area of research in humans.

RESUMEN Antecedentes: La artritis reumatoide (AR) es una enfermedad inflamatoria común mediada por el sistema inmunológico que se caracteriza por una mayor inflamación de la articulación sinovial, y a menudo se asocia con discapacidad. Aunque en varios estudios se han demostrado las propiedades medicinales del durián, se conoce poco sobre el papel de la corteza de madera de durián con fines médicos. Así pues, en este estudio se investigó la actividad antiartrítica del extracto de corteza de madera de durián en un modelo de AR en ratas. Métodos: Las ratas se dividieron en 5 grupos, incluyendo el control, el modelo de AR y el modelo de AR tratado con extracto de corteza de madera durián (20, 30 y 40mg/kg/día durante 14 días). Los efectos del tratamiento se evaluaron mediante cambios clínicos e histológicos en las articulaciones de los tobillos y el nivel de expresión de la sintasa de óxido nítrico inducible (iNOS). Resultados: Desarrollamos con éxito un modelo completo de AR inducida por adyuvantes de Freund (CFA) en ratas, caracterizado por la hinchazón de las extremidades posteriores, los cambios histopatológicos de las articulaciones del tobillo y el aumento de la expresión de la iNOS. La administración de extracto de corteza de madera de durián a una dosis de 40 mg/kg atenuó todos los parámetros analizados en el modelo de AR inducida por CFA en ratas. Conclusión: La mejora de la hinchazón de las extremidades traseras, los cambios histopatológicos y la expresión de iNOS en el modelo de AR indican que el extracto de corteza de madera dura puede considerarse una nueva alternativa de tratamiento para reducir los síntomas de las articulaciones, con un futuro campo de investigación en los seres humanos.

Analgesic effect of Fengshi Qutong Capsules on mice with chronic inflammatory pain caused by complete Freund's adjuvant / 中国中药杂志

The aim was to observe the analgesic effect of Fengshi Qutong Capsules(FSQTC) on chronic inflammatory pain in mice, and investigate its effect on p-ERK/COX-2 signal molecular activity. A model of chronic inflammatory pain was induced in mice by complete Freund's adjuvant(CFA). The mice were divided into normal control group, model group, model+FSQTC 0.3, 0.6 and 1.2 g·kg~(-1 )groups, model+positive control drug ibuprofen(IBP, 0.34 mg·kg~(-1)·d~(-1)) group, and normal control+ FSQTC 1.2 g·kg~(-1)group. FSQTC or IBP was given once a day by oral administration. Standard Von Frey fiber was used to evaluate the mechanical pain threshold, and the acetone stimulation was used to induce inflammatory plantar and observe the cold pain reaction scores. The mechanical pain threshold and cold pain reaction scores were observed before administration and 1, 2, 3, 4, 6 h after administration on the first day, as well as 3 h after administration on the 3 rd to 7 th day. The protein levels of PGE_2, COXs-1,2 and p-ERK in the spinal cord of the inflammatory foot and lumbar 4-5 were detected by enzyme-linked immunosorbent assay, Western blot, immunohistochemistry and immunofluorescence. The results showed that the mechanical pain threshold of the model group decreased and the cold pain reaction score increased as compared with the normal group. FSQTC application could dose-dependently increase the mechanical pain threshold and decrease the cold pain reaction score. The effect lasted for 6 h, most significant at 3 h. The effect of ibuprofen was similar to that of the 0.6 g·kg~(-1) dose group. In addition, FSQTC could reduce the abnormally increased protein content of PGE_2, COX-2 and p-ERK in the inflammatory foot and/or spinal cord of the model group, and the effect was most significant in middle and high dose groups. However, it had no effect on COX-1 in the inflammatory foot and spinal cord of mice. The results suggest that FSQTC has ob-vious analgesic effect on chronic inflammatory pain in mice, which may be related to inhibition of p-ERK/COX-2 signaling pathway.

Evaluation of antiarthritic activity of ginkgolic acid against Freund's adjuvant induced arthritic rat model

This study aimed to analyze the antiarthritic activity of ginkgolic acid against the Complete Freund's Adjuvant (CFA)-induced arthritis in rats. Arthritis was induced through an intradermal injection of CFA (0.1 mL) at the right hind footpad of adult Wistar Albino rats. Ginkgolic acid was administered orally at doses of 25 mg/kg and 50 mg/kg, respectively, once daily via gavage for 25 days upon inducing arthritis. Indomethacin was administered orally at a dose of 3 mg/kg twice in a week which served as positive control group. The animals were sacrificed and subjected to biochemical and histopathological analysis upon completion of treatment. Ginkgolic acid was able to reverse the arthritic effect (p < 0.01) induced by CFA in a dose dependent manner. Swelling of paw, thymus and spleen index, serum biomarker levels, and pro-inflammatory cytokines were significantly reduced (p < 0.01) by the acid whereas the antioxidant enzyme activities were remarkably restored. The histopathological findings were in agreement with the biochemical results. The results indicate that the antioxidant and anti-inflammatory properties of ginkgolic acid can be credited to the antiarthritic effects, and it can be promoted as a potential agent for therapeutic use against osteoarthritis

Development and validation of instrument for assessing patients’ knowledge, attitude, and practice (KAP) on uncomplicated malaria management

Objectives: To develop and validate patients’ knowledge, attitudes, and practice instrument for uncomplicated malaria(PKAPIUM).Material and Methods: A draft PKAPIUM scale was developed after the review of relevant literature and malariatreatment guidelines, and six experts validated its content. Monte Carlo simulation principle was followed in arrivingat 300 patients populations whose data were used to reduce the items based on “Kaiser’s eigenevalue-greater-than-onerule.” This was followed by the test of validity and reliability to assess the psychometric properties of the instrument.Results: The items content validity indices (I-CVI) and the scale CVI (S-CVI) using universal agreement (UA) withinexperts (S-CVI/UA) and average CVI (S-CVI/Ave) approaches were good (0.8–1.00), with absence of items’ floor orceiling effects. Twenty-one items were retained in the new scale arranged under four factors with average varianceextracted (AVE) and square root AVE values of 0.58–0.70 and 0.76–0.84, respectively, suggesting convergent anddiscriminant validities. The goodness-of-fit results [Chi-square (CMIN/DF) = 3.07, p = 0.00], standardized root meansquare residual = 0.070, root mean square error approximation = 0.08 confirmed the hypothesized factor structuresof the scale whose internal consistency of Cronbach’s alpha and composite reliability values were 0.74 and 0.82,respectively, and stability of ICC = 0.92 [95% confidence interval : 0.87–0.95, F = 43 (p = 0.51)].Conclusion: The validity and reliability of the PKAPIUM were in acceptable ranges.

Confirmatory Factor Analysis of the Malay-Language Transtheoretical Model of Physical Activity among Malaysian Primary School Children

@#Introduction: The transtheoretical model (TTM) is an integrative model of intentional change consisting of stages of change, processes of change, decisional balance and self-efficacy. This study aimed at validating the TTM questionnaires on physical activity for Malaysian children using confirmatory factor analysis. Methods: The participants were 381 Malay students (188 male; 193 female), aged 10–12 years old, with a mean age of 10.94 (SD = 0.81). The original version of the TTM was translated into the Malay language using forward and backward translation. Certain phrases were adapted based on the local culture and vocabulary suitable for primary school students. Results: The final measurement models and their fit indices were: processes of change (CFI = 0.939, TLI = 0.925, SRMR = 0.040, RMSEA = 0.030); decisional balance (CFI = 0.897, TLI = 0.864, SRMR = 0.045, RMSEA = 0.038); and self-efficacy (CFI = 0.934, TLI = 0.915, SRMR = 0.042, RMSEA = 0.032). Conclusion: Care must be taken when using the TTM with children, as it has been prevalently validated with adults. The final version of the TTM questionnaire for Malay primary school children had 24 items for process of changes, 13 items for self-efficacy and 10 items for decisional balance.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles

Nanoparticles are considered to be a powerful approach for the delivery of poorly water-soluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation (FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles, polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer (CIJM), multi-inlet vortex mixer (MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly water-soluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.

Effect of Xiao Chaihutang on NF-κB Signaling Pathway in Synovial Tissue of CFA Rats / 中国实验方剂学杂志

Objective:To observe the expression of tumor necrosis factor receptor-associated death domain (TARDD), nuclear transcription factor-κB inhibiting protein α(IκBα)IκB kinase-α (IKKα) and nuclear transcription factor (NF)-κB p65 protein in the NF-κB signaling pathway of synovial tissues of complete Freund's adjuvant (CFA) rats after treatment with Xiao Chaihutang (XCHT). Method:In animal experiments, SPF health adult female Wistar rats were used to prepare the CFA animal model of rats with rheumatoid arthritis with Freund's complete adjuvant and cattle Ⅱ collagen type. According to the random number table, the rats were randomly divided into the normal group, the model group, the low-dose XCHT group, the medium-dose XCHT group, the high-dose XCHT group, and the Tripterygium glucosides group. The drugs were given at 7 d after the model was built. Both normal group and model group were given water for injection,and low-dose XCHT group(5.94 g·kg-1),medium-dose XCHT group(11.88 g·kg-1),high-dose XCHT group(23.76 g·kg-1),Tripterygium glucosides group(0.006 3 g·kg-1) were given corresponding drugs by gavage for three times a day, 2 mL/time. The histopathology of rat ankle joint was observed, and the protein expressions of TARDD,IKKα,IκBα,NF-κB p65 in the NF-κB signaling pathway in synovial tissue of CFA rats were detected by Western blot. Result:With the increase of the dosage of XCHT, the histopathological score of the right posterior ankle joint of the experimental rats was increased. And in the protein expressions of TARDD,IKKα,IκBα,NF-κB p65 in NF-κB signaling pathway in Synovial Tissue of CFA rats, compared with the model group, the statistical results of the low-dose XCHT group showed decreased protein expressions (PPPα, IκB α, NF-κB p65 in the NF-κB signaling pathway were significantly increased (PPα, IκBα, NF-κB p65 key protein expressions in the NF-κB signaling pathway and protein expressions in low-dose XCHT group were obviously lower (PPConclusion:This study shows that as the dose of Xiao Chaihutang increases, it could effectively improve synovitis, and suppress the expressions of key proteins in the inflammatory signaling pathway of NF-κB, thereby preventing inflammation and suppressing bone erosion.

In vivo anti-arthritic and antioxidant effects from the standardized ethanolic extract of Moussonia deppeana

ABSTRACT Moussonia deppeana (Schltdl. & Cham.) Klotzsch ex Hanst., Gesneriaceae, known as tlachichinole, is a Mexican medicinal plant used for treatment of chronic inflammation-related diseases such as arthritis. In this paper, the main metabolite verbascoside was quantified in ethanolic extract; anti-arthritic and antioxidant activities were also evaluated in Complete Freund's Adjuvant induced arthritis in mice, with complete hematological evaluation, and oxidative stress measure in edema and ganglionic tissues on day 28. In popliteal ganglion, CD4+ lymphocytes and tumor necrosis factor alpha concentration were measured in addition to histological analysis. Ethanolic extract contained 79.2 mg of verbascoside/g extract, and this extract at 450 mg/kg generated an inhibition of 24% over paw edema development and increased body weight gain on final day. For hematological parameters, same dose decreased total leukocytes and lymphocytes, as well as decreased oxidation rate over biomolecules in edema and ganglionic tissues, and increased antioxidant enzyme activity. In ganglionic tissue, CD4+ lymphocytes and tumor necrosis factor alpha level showed no differences at any tested dose compared to complete Freund's adjuvant untreated group. Histological analysis of popliteal ganglion revealed moderate reduction of follicular hyperplasia, leukocyte infiltration and lipid inclusions at 450 mg/kg dose. Ethanolic extract of M. deppeana possesses anti-edematous activity associated to a moderate reduction in follicular hyperplasia, with immune-modulatory and antioxidant effects during experimental arthritis in mice.

Psychometric properties of the Brief-COPE for the evaluation of coping strategies in the Chilean population

Abstract The Brief-COPE is an abbreviated version of the COPE (Coping Orientation to Problems Experienced) Inventory, a self-report questionnaire developed to assess a broad range of coping responses. Currently, it is one of the best validated and most frequently used measures of coping strategies. The aim of this study was to validate a culturally appropriate Chilean version of the Brief-COPE, assess its psychometric properties and construct and congruent validity. The Spanish version of the Brief-COPE was administrated in a community sample of 1847 Chilean adult (60.4% women) exposed to a variety of stressful experiences. The factorial structure of the inventory was examined by comparing four different models found in previous studies in Latin American population. The results of confirmatory factor analyses revealed, as in the original studies, a 14-factor structure of the Brief-COPE. These dimensions showed adequate internal structure and consistency. The factorial invariance comparing women and men confirmed strict invariance. Additionally, the results showed significant correlation between some Brief-COPE scales, such as denial and substance use, with perceived stress and emotional support and active coping with subjective well-being. Overall, the present work offers a valid and reliable tool for assessing coping strategies in the Chilean population.

Validez y confiabilidad de la Escala de Percepción de Riesgo de Deslave en la Ciudad de México / Validation and reliability of the Scale of Landslide Risk Perception in Mexico City

Resumen: El objetivo del estudio fue generar un instrumento confiable y válido que permita evaluar la percepción del riesgo de deslave en habitantes de asentamientos urbanos vulnerables a riesgos geológicos en la ciudad de México. Se construyó una escala conformada por 9 reactivos con 5 opciones de respuesta; para obtener las propiedades psicométricas óptimas se aplicó a 217 habitantes de entre 18 y 86 años de edad, 126 mujeres y 91 hombres. El análisis de la estructura factorial y la confiabilidad proporcionan una escala final constituida por 6 reactivos organizados en 2 factores, con apropiados índices de bondad de ajuste. Se concluye que la Escala de Percepción de Riesgo de Deslave proporciona información relevante para la toma de decisiones ante fenómenos naturales extremos en la ciudad de México.

Abstract: The main objective of this study was to develop a valid and reliable scale that assessed the risk perception in urban settlements vulnerable to geological hazards in Mexico City. The scale included 9 items with 5 optional answers. In order to obtain optimum psychometric properties, the scale was applied to 217 inhabitants between the ages of 18 and 86, from which 126 were women and 91 men. The analysis of factorial structure and the reliability provide a final scale made up from 6 items organized in 2 factors with satisfactory goodness of fit (df = 8; χ2 = 14.138; P = .078; CFI = .990; RMSEA = .060). It is concluded that the Scale of Landslide Risk Perception provides relevant information for decision-making to extreme natural phenomena in Mexico City.

Inventario de Conductas Infantiles en preescolares: propiedades psicométricas del Inventario de Conductas Infantiles (CBCL/1. 5-5) y del informe del cuidador/educador (C-TRF) en preescolares chilenos / Psychometric properties of the Child Behavior Checklist and the caregiver /teacher report form in Chilean preschoolers

El Inventario de Conductas Infantiles 1.5-5 años (CBCL/1.5-5 por su acrónimo en inglés) y el informe del cuidador/educador (C-TRF por su acrónimo en inglés), son de los instrumentos más ampliamente reconocidos internacionalmente para evaluar conductas desadaptativas que pueden afectan el desarrollo presente y futuro de niños y niñas preescolares. Se evaluó el comportamiento psicométrico de ambos instrumentos en una muestra diversa socioeconómicamente de 550 preescolares chilenos. En general, ambos mostraron un comportamiento psicométrico análogo al obtenido con estudios en otras sociedades. Los análisis factoriales confirmatorios mostraron un ajuste adecuado del modelo bifactorial original. Sin embargo, en el CBCL/1.5-5 los puntajes obtenidos son más altos que en la mayoría de los países y, comparativamente, en ambos instrumentos, se observó un mayor efecto de género. Se analizan los hallazgos obtenidos, y se dan sugerencias normativas y conceptuales para el empleo de ambos instrumentos en niños y niñas preescolares en nuestro país.

The child Behavior checklist/1.5-5 and the caregiver/teacher report Form are one of the most widely internationally recognized instruments to evaluate desadaptative behaviors which may affect the current and future development of preschool children. The psychometric behavior of both instruments was evaluated in a socioeconomically diverse sample of 550 chilean preschool children. In general, it was observed an analog behavior of both compared to the one obtained with studies in other societies. The confirmatory factor analysis showed a suitable adjustment of the original bifactor model. However, in the CBCL, the scores obtained are higher than in most of the countries and, comparatively, in both instruments, a greater effect of gender was observed. The findings obtained are analyzed and, normative and conceptual suggestions are given for the use of both instruments in preschool children in our country.

In vitro and In vivo Anti-Arthritic Activity of Combined Ethanolic Extracts of Pisonia grandis and Cardiospermum halicacabum in Wistar Rats.

The combined Bi-herbal ethanolic extract (BHE) made up of equal quantities of leaves of Pisonia grandis and Cardiospermum halicacabum was evaluated for its synergistic in vitro and in vivo Anti-arthritic effects and was compared with its individual ethanolic extracts of Pisonia grandis (EPG) and Cardiospermum halicacabum (ECH). The inhibition of protein denaturation, membrane stabilization and proteinase enzyme inhibition were studied as in vitro and Freund’s adjuvant arthritis model in Wistar rats was used to study the in vivo Anti-arthritic activity. The three extracts (BHE, EPG, and ECH) at the dose level of 300mg/kg b.w.in 2%CMC were ingested orally to the CFA treated rats once daily for 40 days and the percentage inhibition of the paw volume increase due to the drug treatment was calculated. All the three plant extracts exhibited dose dependent stabilization of the RBC membranes, inhibition of protein denaturation and protease inhibition. The BHE has got a significant reduction in the paw volume and oedema when comparable to EPG and ECH in these intoxicant treated animals. These observed effects may be due to its inhibition of free radical production due to the immunological and inflammatory reactions or minimizing protein denaturation or proteinase enzyme or stabilizing the membranes.

Participation of IL-1β in temporomandibular nociception in rats with CFA-induced inflammation

The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of IL-1β in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, IL-1β plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of IL-1β is a potential therapeutic target for inflammatory TMJ pain.

Characterization of coal fly ash nanoparticles and their induced in vitro cellular toxicity and oxidative DNA damage in different cell lines.

Coal combustion generates considerable amount of ultrafine particles and exposure to such particulate matter is a major health concern in the developing countries. In this study, we collected nano sized coal fly ash (CFA) and characterized them by scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX), particle size analyzer (PSA) and transmission electron microscope (TEM), and investigated its toxicity in vitro using different cell lines. The imaging techniques showed that the coal fly ash nanoparticles (CFA-NPs) are predominately spherical shaped. The analyses have revealed that the CFA-NPs are 7-50 nm in diameter and contain several heavy metals associated with CFA particles. The studies showed significant amount of toxicity in all cell lines on treatment with CFA-NPs. The cytotoxicity and oxidative DNA damage caused by CFA-NPs were determined by inhibition of cellular metabolism (MTT), total intracellular glutathione (GSH), reactive oxygen species (ROS) and DNA fragmentation in cultured cell lines (Chang liver, HS294T and LL29). The cellular metabolism was inhibited in a dose-dependent manner in CFA-NPs treated cell lines. The CFA-NPs induced ROS and decreased the total intracellular glutathione with increased dose. Further, the CFA-NPs treated cells showed severe DNA laddering as a result of DNA fragmentation.

Botulinum Toxin Type A Attenuates Activation of Glial Cells in Rat Medullary Dorsal Horn with CFA-induced Inflammatory Pain

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of 40 microL CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

Efeitos de um minuto e dez minutos de deambulação em ratos com artrite induzida por adjuvante completo de Freund sobre os sintomas de dor e edema / Effects of one minute and ten minutes of walking activity in rats with arthritis induced by complete Freund's adjuvant on pain and edema symptoms

Este estudo avaliou o efeito de dois protocolos de exercício na nocicepção, edema e migração celular em ratos com artrite induzida por CFA. Ratos Wistar fêmeas (200 - 250 g, n = 50) foram induzidos à monoartrite por adjuvante completo de Freund (CFA, Mycobacterium butyricum; 0,5 mg/mL; 50 μL) na articulação do joelho direito (TF; n = 24) ou tornozelo direito (TT; n = 26). A incapacitação articular foi mensurada pelo tempo de elevação da pata (TEP; s) em 1 minuto de avaliação. O edema do joelho ou tornozelo foi avaliado pela medida do diâmetro articular (AD, cm) e pelo edema de pata (EP, mL), respectivamente. Ambos foram avaliados durante 10 dias consecutivos. Dois protocolos de exercício foram realizados: (a) exercício constante (TF, n = 6; TT, n = 6), realizando 1 minuto diário de exercício no cilindro (3 r.p.m.); (b) exercício variável (TF, n = 6; TT, n = 7), exercício com aumento de 1 minuto por dia, totalizando 10 minutos no último dia. Os grupos-controle (TF, n = 12; TT, n = 13) não realizaram exercício. Após 10 dias, os animais foram eutanasiados para contagem total (células/mm3) e diferencial (mononucleares e polimorfos nucleares; células/mm3) de leucócitos do tecido inflamado. O exercício variável inibiu a incapacitação e o edema em ambas as articulações. Entretanto, reduziu a migração total de leucócitos apenas na articulação TF. O exercício constante inibiu o edema nas duas articulações e reduziu a migração total de leucócitos da articulação TT. Porém, não reduziu a incapacitação. O exercício variável pareceu ser mais efetivo em reduzir os parâmetros inflamatórios em comparação com o exercício constante.

This study evaluated the effects of two protocols of exercise on nociception, edema and cell migration in rats with CFA-induced arthritis. Female Wistar rats (200 - 250 g, n = 50) was monoarthritis-induced by complete Freund's adjuvant (CFA; Mycobacterium butyricum, 0.5 mg/mL; 50 μL) into the right knee joint (TF; n = 24) or right ankle joint (TT; n = 26). Incapacitation was measured by the paw elevation time (TEP; s) in 1-min periods of observation. The edema of the knee or ankle joints was evaluated by the variation of the articular diameter (DA, cm) and by the paw volume variation (EP, mL), respectively. Both were measured during 10 consecutive days. Two protocols of exercise were performed: (a) in the constant exercise group (TF, n = 6; TT, n = 6) performing 1 minute of daily exercise on the cylinder; (b) variable exercise group (TF, n = 6; TT, n = 7), the exercise increased by 1 minute per day. The control groups (TF, n = 12; TT, n = 13) didn´t perform the exercise. After 10 days, the animals were euthanized for total (CT; cells/mm3) and differential leukocyte counts (mononuclear - MON, and polymorphonuclear - PMN, cells/mm3) of the articular inflammatory exudate. The variable exercise protocol inhibited incapacitation and edema for both joints. However, cell migration decreased only in the TF.The constant exercise reduced edema in both joints, and cell migration was decreased in the TT. However, the incapacitation was not reduced. Variable exercise seemed to be more effective in reducing the inflammatory parameters than constant exercise.

Análisis factorial de las puntuaciones del CADRI en adolescentes universitarios españoles / Factor Analysis of Scores CADRI in Spanish College Teenagers

El estudio de la violencia en las relaciones de pareja adolescentes suscita interés, si bien el número de instrumentos disponibles para tal fin es reducido. El objetivo del estudio es examinar la validez estructural del Conflict in Adoslescent Dating Relationship Inventory (CADRI). En el estudio, participan 571 sujetos de nacionalidad española (171 hombres y 400 mujeres) de 17 a 21 años de edad (M = 18.76; DE = 1.204). Los resultados establecen un modelo de violencia sufrida y un modelo estructural de violencia cometida con valores de ajuste adecuados, saturaciones significativas e índices de consistencia interna elevados. Cada uno de los modelos propuestos está formado por cuatro factores: violencia física, violencia verbal, violencia relacional y estilo de solución de conflictos.

The study of adolescent relationship violence arouses vast interest but unfortunately the tools available for this purpose are limited. This study aims to verify the structural validity of the Conflict in Adolescent Dating Relationship Inventory (CADRI). 571 Spaniards subjects (171 males and 400 females) aged 17 to 21 (M = 18.76; SD = 1.208) took part in the study. Results show a model for suffered violence and another structural one for committed violence, both revealing adequate fit indexes, significant saturations and high internal consistency indexes. Each one of the models proposed comprises four factors: physical violence, verbal violence, relational violence and style of conflict resolution.

Participation of Central P2X7 Receptors in CFA-induced Inflammatory Pain in the Orofacial Area of Rats

We investigated the role of central P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawley rats weighing 230-280g. Complete Freund's adjuvant (CFA, 40 microL) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. The intracisternal administration of iso-PPADS tetrasodium salt, a non-selective P2X receptor antagonist, A317491 sodium salt hydrate, a P2X2/3 receptor antagonist, 5-BDBD, a P2X4 receptor antagonist, or A438079 hydrochloride, a P2X7 receptor antagonist, was performed 5 days after CFA injection. Subcutaneous injections of CFA produced increases in thermal hypersensitivity. Intracisternal injections of iso-PPADS (25 microg) or A438079 (25 or 50 microg) produced significant anti-hyperalgesic effects against thermal stimuli compared to the vehicle group. A317491 or 5-BDBD did not affect the head withdrawal latency times in rats showing an inflammatory response. Subcutaneous injections of CFA resulted in the up-regulation of OX-42, a microglia marker, and GFAP, an astrocyte marker, in the medullary dorsal horn. The intracisternal administration of A438079 reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that a blockade of the central P2X7 receptor produces antinociceptive effects, mediated by inhibition of glial cell function in the medullary dorsal horn. These data also indicate that central P2X7 receptors are potential targets for future therapeutic approaches to inflammatory pain in the orofacial area.

Effectiveness of GABA agonist for treatment in mice with complete freud’s adjuvants induced chronic pain: molecular modeling approach.

The present study was designed to investigate the effectiveness of gaba agonist in behavioral changes of inflammatory mice with molecular docking approach. Forty mice were divided into 8 groups i.e. sham, gabapentin (10, 30 and 100 nmol), baclofen (1, 10 and 30 nmol) and negative control. Chronic pain was induced by inflammatory agent such as Complete Freud’s Adjuvant (CFA). On day 8 after intraplantar injection of CFA, mice were treated by intrathecal with normal saline (sham and negative control groups), gabapentin and baclofen with three different doses, once a day for seven consecutive days. Latency time toward thermal stimulus was measured on days 1,2,8,9,11 and 15 after induction. The molecular docking was examined by Mollegro virtual docker program. The result showed that intrathecal injection of gabapentin and baclofen increased time latency toward thermal stimulus compared to negative control. There were differences between gabapentin and baclofen doses for chronic pain treatment. Molecular docking showed that the differences of effective dose were related to type of amino acid binding between gabapentin and baclofen.