Ketoprofen is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of ketoprofen can cause gastric irritation and adverse renal effects. Transdermal delivery of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug concentrations at the site of administration. The release of ketoprofen from proprietary gel products from three different countries was evaluated by comparing the in vitro release profiles. Twenty extemporaneously prepared ketoprofen gel formulations using Carbopol® polymers were manufactured. The effect of polymer, drug concentration, pH and solvent systems on the in vitro release of ketoprofen from these formulations were investigated. The gels were evaluated for drug content and pH. The release of the drug from all the formulations obeyed the Higuchi principle. Two static FDA approved diffusion cells, namely the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell, were compared by measuring the in vitro release rate of ketoprofen from all the gel formulations through a synthetic silicone membrane. High-performance liquid chromatography and ultraviolet spectrophotometric analytical techniques were both used for the analysis of ketoprofen. The validated methods were employed for the determination of ketoprofen in the sample solutions taken from the receptor fluid. Two of the three proprietary products registered under the same manufacturing license exhibited similar results whereas the third product differed significantly. Among the variables investigated, the vehicle pH and solvent composition were found have the most significant effect on the in vitro release of ketoprofen from Carbopol® polymers. The different grades of Carbopol® polymers showed statistically significantly different release kinetics with respect to lag time. When evaluating the proprietary products, both the modified Franz diffusion cell and the European Pharmacopoeia diffusion cell were deemed adequate although higher profiles were generally obtained from the European Pharmacopoeia diffusion cells. Smoother diffusion profiles were obtained from samples analysed by high-performance liquid chromatography than by ultraviolet spectrophotometry in both diffusion cells. Sample solutions taken from Franz diffusion cells and analysed by ultraviolet spectrophotometry also produced smooth diffusion profiles. Erratic and higher diffusion profiles were observed with samples taken from the European Pharmacopoeia diffusion cell and analysed by ultraviolet spectrophotometry. The choice of diffusion cells and analytical procedure in product development must be weighed against the relatively poor reproducibility as observed with the European Pharmacopoeia diffusion cell.

Alarmins and damage associated molecular pattern (DAMP) are endogenous proteins with distinct and various intracellular roles that when released extracellularly act as startingsignals for inflammatory immune responses. The endogenous protein High mobility group box 1 (HMGB1) acts as a DAMP and has been shown to drive progression of multiple inflammatory and autoimmune diseases. During homeostasis HMGB1 is localized in the nucleus of almost any cell, where its main function is organization of the DNA and regulation of transcription. Upon cell death or immune cell activation HMGB1 can be translocated into the cytoplasm for subsequent release into the extracellular space. Extracellular HMGB1 can act as a DAMP by activating several receptors of the immune system. Recent studies focus on HMGB1 release and functional regulation due to prost-translational modifications (PTMs) on cysteine residues. However, little is known about enzymatic regulation of HMGB1. The aim of this thesis was to investigate the possibility of proteolytic processing of HMGB1 by enzymes, which play a crucial role in inflammatory diseases and their progression. We utilized an in vitro model that mimics natural conditions of the autoimmune disease arthritis. Enzymatic digestion of HMGB1 was performed in kinetics studies using the neutrophilic enzymes cathepsin G, neutrophil Elastase as well as matrix metalloproteinase-3, which is released from tissues at the site of inflammation. We defined that HMGB1 is a novel substrate of all of the tested enzymes. All enzymes induced different cleavage pattern. In conclusion, my findings open up the possibility for future studies involving the observed fragments of HMGB1 and their functional features. It also demonstrated that HMGB1 is affected by protease modifications in a disease relevant environment.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martina Kobrlová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Pharmacogenetics in rheumatoid arthritis Based on scientific progress in the research of human genome and the discovery of polymorphisms, which are involved in the interindividual differences in human population, there is also a growing interest in pharmacogenetics. It is a field combining pharmacology and genetics with the aim of identifying specific features that could explain the different responses of patients to treatment by clinically used drugs. Applying this knowledge could contribute to a simpler choice of medication for a particular patient and it could reduce the risk of side effects or poor response. In this diploma thesis I dealt with the latest scientific knowledge on pharmacogenetics in rheumatology, in particular the rheumatoid arthritis. From available studies, reviews, and meta-analyzes that have been published, I summarized current data on the relationship between polymorphisms and disease modifying drugs (DMARDs) used for the treatment of this disease. The largest amount of data was found on the most commonly used methotrexate. Further, the work examines the leflunomide and other...

Reumatoid artrit är en progressiv inflammatorisk sjukdom som bland annat orsakar smärta och fatigue i kroppen där hela personen och dess liv påverkas. Brist på kunskap om hur det är att leva med reumatoid artrit kan leda till att personer inte får den vård de behöver. Syftet med litteraturstudien var att belysa erfarenheter av att leva med reumatoid artrit. Studien genomfördes som en litteraturstudie. Databassökningar gjordes systematiskt med sökord som var relevanta utifrån syftet. Litteraturstudien baserades på åtta kvalitativa artiklar som kvalitetsgranskades och analyserades, vilka resulterade i två teman, begränsningar och strategier. Erfarenheterna av att leva med reumatoid artrit var att symtomen begränsade personen i det dagliga livet. För att hantera begränsningarna och ta sig vidare i livet krävdes planering och acceptans. Genom att fokusera på det som var bra insåg personerna att de är så mycket mer än sjukdomen. Personcentrerad vård är en av sjuksköterskans kärnkompetenser som fokuserar på att se hela människan utifrån respekt och lyhördhet vilket leder till individualiserad vård där personer känner sig sedda och hörda. / Rheumatoid arthritis is a progressive inflammatory disease that causes pain and fatigue. The whole individual and their life is affected by living with rheumatoid arthritis. Lack of knowledge about living with rheumatoid arthritis can lead to that people don´t get the care they need. The purpose of the literature study was to highlight experiences of living with rheumatoid arthritis. The study was conducted as a literature study. Database searches were made systematically using keywords relevant to the purpose. The literature study was based on eight qualitative articles which were analyzed and graded for quality. The themes of the result were limitations and strategies. The experience of living with rheumatoid arthritis was that the symptoms limited the person and their daily life. To manage the constraints and move on in life, planning and acceptance were required. By focusing on what was good, the people realized that they were so much more than the disease. Person-centered care is one of the nurse's core competencies, focusing on seeing the whole human being based on respect and responsiveness, which leads to individualized care where people feel seen and heard.

There is little head-to-head evidence comparing interventions available for juvenile idiopathic arthritis (JIA). This review involved a series of systematic reviews and network meta-analyses (NMAs) to evaluate the comparative efficacy and safety of pharmacological and non-pharmacological interventions among patients with JIA. Outcomes were the American College of Rheumatology Pediatric 30 (ACR Pedi 30) (disease response), its six composite outcomes, pain relief, health-related quality of life, and physical and emotional functioning. There was some evidence that etanercept had greater reduction in the number of joints with active arthritis compared to abatacept for polyarticular-course JIA and that canakinumab had improved ACR Pedi 30 over rilonacept. Non-pharmacological interventions showed no significant results for efficacy but were safe overall. Most included studies were low-quality and many were excluded from analysis because of unclear reporting or no results for outcomes of interest. As more studies are conducted this will improve the estimates from the NMAs.

Les monocytes inflammatoires Ly-6Chigh murins, et leurs homologues humains CD14+CD16-, jouent un rôle important dans l'initiation et la persistance des maladies inflammatoires chroniques. Leur action délétère dans ces pathologies a mené au développement de stratégies thérapeutiques visant à les éliminer ou empêcher leur recrutement aux sites inflammatoires. Toutefois, ces méthodes se sont avérées peu spécifiques des monocytes et surtout d'une faible efficacité compte tenu de l'aspect hautement inflammatoire des monocytes. Le besoin de développer de nouvelles stratégies est donc nécessaire. Les objectifs de ma thèse ont donc été dans un premier temps de caractériser in vivo le ciblage spécifique des monocytes inflammatoires par la formulation liposomale DMAPAP. Dans un second temps, l'utilisation de DMAPAP pour formuler des siRNA a permis d'évaluer l'efficacité thérapeutique d'une stratégie basée sur l'inhibition spécifique de gènes jouant un rôle clef dans l'inflammation dans les monocytes inflammatoires. Mon travail a permis de montrer dans un modèle préclinique d'arthrite que l'inhibition de gènes régulateurs de l'inflammation dans les monocytes Ly-6Chigh est une approche thérapeutique efficace permettant d'induire une immunomodulation des réponses pathogéniques des lymphocytes T effecteurs, aboutissant au défaut de recrutement des cellules immunitaires dans les articulations et à une amélioration des signes cliniques. J'ai également validé le transfert de cette technologie ex vivo sur cellules humaines primaires. L'inhibition de gènes clefs dans les monocytes inflammatoires représente donc une stratégie prometteuse pour le développement de futures thérapies dans la polyarthrite rhumatoïde. Par ailleurs, mes résultats confirment le rôle central des monocytes inflammatoires dans les pathologies inflammatoires chroniques. / Inflammatory mouse Ly6Chigh monocyte subset and its human counterpart, defined as CD14+ CD16-, play key roles in the initiation and chronicization of immune-mediated inflammatory disorders (IMID). Deleterious effects of monocytes led to the development of therapeutic strategies aiming at depleting them or preventing their recruitment to inflamed tissues. However, these methods are poorly specific with weak efficacy considering the high number of inflammatory monocytes and their marked level of activation. The need for developing new therapeutic approaches is obvious. The aim of my thesis was to characterize selective delivery of a siRNA-containing lipid formulation to the Ly-6Chigh monocyte population and at evaluating the therapeutic potential of this targeted strategy. Using the cationic lipid-based DMAPAP vehicle for in vivo RNAi-mediated gene silencing, my work allowed demonstrating, in a preclinical mouse model of arthritis, the efficacy to inhibit master genes of inflammation specifically within Ly-6Chigh monocytes upon systemic injection. Reduced disease severity in mice was associated with an overall systemic immunomodulation of the pathogenic T cell populations and led to defective mobilization of immune cells to arthritic joints. Importantly, the formulation was successfully optimized in a perspective of clinical application and the targeting of human CD14+CD16- inflammatory monocytes was validated ex vivo. Overall, my findings demonstrate that the silencing of a key gene within Ly-6Chigh monocytes is a promising strategy for future therapeutic intervention in the context of IMID and reinforces the pivotal role of Ly-6Chigh monocytes in inflammatory processes.

Immunomodulation de l'arthrite expérimentale par les cellules dendritiques tolérogènes. Les cellules dendritiques (DCs) sont des cellules présentatrices d'antigènes jouant un rôle clé dans l'initiation et la modulation des réponses immunitaires. En effet, en parallèle de leur capacité à initier une réponse immunitaire adaptative, les DC sont également impliquées dans les mécanismes de tolérance périphérique. Elles sont utilisées depuis 10 ans maintenant en clinique dans des stratégies thérapeutiques anti-tumorale et leurs propriétés tolérogènes ouvrent aujourd'hui leur champ d'applications à des pathologies autoimmunes, l'asthme et la transplantation afin de restaurer une homéostasie de la réponse immune. Les objectifs de ma thèse ont consisté à :- renforcer le potentiel tolérogène des DCs par manipulation in vitro- tester la capacité de DCs tolérogènes à induire une protection de l'arthrite expérimentale- identifier les mécanismes cellulaires et moléculaires impliqués dans la tolérance induite par les DCs. Mon travail de thèse a permis de montrer l'efficacité de la vaccination de souris arthritiques avec des DCs immatures conservant leurs propriétés tolérogènes in vitro et in vivo, grâce au traitement préalable avec un agent immunosuppresseur, la rapamycine. L'injection répétée de DCs immatures induit la génération de lymphocytes T régulateurs CD4+ CD49b+ sécrétant de l'IL-10 ayant de fortes capacités immunosuppressives. Ce projet a permis de mettre en évidence l'efficacité des DCs dans le traitement d'une pathologie autoimmune déjà établie et l'implication d'une population cellulaire régulatrice originale. / Tolerogenic dendritic cells for immumodulation in experimental arthritis.Dendritic cells (DCs) are the most potent antigen-presenting cells that play critical roles in the initiation and regulation of immune responses. Based on their tolerogenic properties, DCs offer potential as therapeutic tools to ameliorate or prevent graft rejection or graft-versus-host disease, or to treat autoimmune disorders.The objectives of my PhD consisted to:- reinforce the tolerogenic potential of DCs by in vitro handling.- assess the capacity of such tolerogenic DCs to induce a protective response in experimental autoimmune arthritis- identify cellular and molecular mechanisms implied in the tolerogenic DCs-induced protectionOur results suggest that, in contrast with conventional DCs, the rapamycin-conditioned iDCs maintain their tolerogenic potential upon injection in inflammatory settings and are able to dampen an already Th1-primed immune response, conferring a protection from arthritis. The protection of the mice was associated with an expansion of the IL-10-secreting CD49b+ Treg in the spleen and liver of the injected mice and a decrease of the Th1 immune response. These results underscore the therapeutic potential of tolerogenic DCs in an established autoimmune disease as well as the anti-inflammatory potential of the CD49b+ Treg cell population induced following DC vaccination.

OBJETIVOS: Avaliar o perfil e o número absoluto e percentual de células NK verdadeiras (CD56+CD16+CD3-) e de células NK e NKT (CD56+) no sangue periférico de uma coorte de pacientes com artrite reumatóide (AR) antes e durante o tratamento com rituximabe (RTX). MÉTODOS: Foram analisados dez pacientes do grupo controle (doadores de sangue) e dez pacientes com AR que receberam duas infusões de RTX 1g separadas por intervalo de 14 dias. As análises imunofenotípicas para avaliação do perfil e quantificação de células NK foram realizadas pré e após a infusão ou até a recaída clínica. Pacientes respondedores e não respondedores foram classificados de acordo com os critérios do Colégio Americano de Reumatologia (ACR) em 6 meses. RESULTADOS: A quantidade de células NK verdadeiras não demonstrou variação significativa pré e após o tratamento com RTX. Contudo, houve aumento percentual de células CD56+ entre o primeiro e o segundo mês após a infusão com RTX. Além disso, os pacientes respondedores apresentaram uma tendência de aumento do número absoluto de células NK verdadeiras após dois meses de tratamento. Já em relação ao grupo controle, observou-se um aumento significativo do número de células NK basais nos pacientes com AR (p<0,05). CONCLUSÕES: Foi identificada uma tendência de aumento nos valores absolutos de células NK verdadeiras entre os pacientes respondedores no segundo mês após a infusão com RTX. Não foi identificada uma variação significativa no perfil e quantidade de células NK nos pacientes com AR pré e após o tratamento com RTX. Contudo, foi observado que os pacientes com AR possuem uma quantidade maior de células NK do que os controles, sugerindo um possível envolvimento destas células na AR. / OBJECTIVES: To assess the profile as well as the absolute number and percentage of true NK cells (CD56+CD16+CD3-), and NK and NKT cells (CD56+) in the peripheral blood of a cohort of patients with rheumatoid arthritis (RA) before and during rituximab (RTX) therapy. METHODS: Ten control patients (blood donors) and ten patients with RA were assessed. The latter group received two intravenous infusions of 1g RTX, separated by a 14 day interval. Immunophenotypic analyses of NK cells were conducted before and after infusion, or until clinical relapse. After six months, respondents and nonrespondents were reassessed according to American Rheumatology Criteria (ARC). RESULTS: The number of true NK cells did not significantly change after treatment with RTX. However, an increase in the percentage of CD56+ cells was observed between the first and second month after RTX infusion. Respondents also displayed a tendency toward an increased number of true NK cells after two months of treatment. At baseline, the number of NK cells was also found to be significantly higher in patients with RA than in control individuals (p<0.05). CONCLUSIONS: Respondents displayed a tendency toward an increase in the absolute number of true NK cells in the second month after RTX infusion. No significant changes in the profile and frequency of NK cells were found between preand post-RTX treatment assessments of patients with RA. However, it was found that patients with RA have a higher number of NK cells than control partcipants, suggesting a possible role of these cells in RA.

Orientador: Evanisi Teresa Palomari / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-27T08:27:28Z (GMT). No. of bitstreams: 1 Lemos_GeorgeAzevedo_M.pdf: 2430384 bytes, checksum: e0763d6d63c12784a5888085434f8dd8 (MD5) Previous issue date: 2015 / Resumo: A Disfunção temporomandibular (DTM) é uma expressão coletiva que engloba vários sinais e sintomas clínicos relacionados aos músculos da mastigação, articulações temporomandibulares (ATMs) e estruturas associadas. As principais queixas relatadas são ruídos e dor na região da ATM, com maior prevalência em adultos jovens, especialmente mulheres. A inflamação intra-articular é considerada uma das mais importantes fontes de dor nesta disfunção. O processo inflamatório pode se localizar na membrana sinovial, cápsula articular ou tecidos retrodiscais, e na presença de alterações degenerativas articulares recebe o nome de artrite. Assim, o laser de baixa potência (LBP) e o hialuronato de sódio de alto peso molecular (HSAPM) tem sido utilizados para o tratamento de distúrbios inflamatórios da ATM e, resultados clínicos promissores têm sido descritos. Estudos experimentais, sob a óptica da biologia celular e molecular, fazem-se necessários para melhor compreensão de seus respectivos efeitos biológicos e elaboração de protocolos clínicos seguros. Desta forma, o objetivo do presente estudo foi caracterizar a ação morfológica e bioquímica da terapia com LBP e HSAPM sobre a artrite induzida na ATM. Utilizou-se 48 ratos machos, Wistar, divididos nos grupos: GA, animais com artrite induzida por meio de injeção intra-articular de adjuvante completo de Freund (CFA); GL, animais com artrite e tratados com LBP; GH, animais com artrite e tratados com HSAPM e; GHL, animais com artrite e tratados com LBP e HSAPM. Todos os experimentos ocorreram na ATM esquerda. As ATMs direitas no GA foram utilizadas como controle (GC). Foram realizadas análises morfológicas por meio de cortes corados em hematoxilina-eosina (HE), azul de toluidina e Picrosirius. Nos discos articulares, também foram realizadas análises histomorfométricas e birrefringência de fibras colágenas (microscopia de polarização). As análises bioquímicas dos tecidos da ATM foram realizadas por meio de dosagens de glicosaminoglicanos sulfatados (GAGs) e zimografia para avaliação das metaloproteinases (MMPs) 2 e 9. Os dados obtidos foram analisados por meio dos testes ANOVA one-way com pós-teste de Tukey e, Kruskal-Wallis seguido do pós-teste de Dunn. O GA exibiu acentuadas alterações morfológicas nos componentes da ATM tais como: elevada espessura do disco articular; hiperplasia da membrana sinovial e formação de pannus; reabsorção óssea da fossa mandibular; aplainamento do côndilo mandibular e presença de intenso infiltrado de células inflamatórias mononucleares no tecido subsinovial. A microscopia de polarização mostrou menor birrefringência das fibras colágenas, indicando alto grau de desorganização das fibras colágenas. Os GL, GH e GHL apresentaram menor espessura do disco articular e maior birrefringência das fibras colágenas em comparação ao GA (p<0,05). Na análise bioquímica, ficou demonstrado que a concentração de GAGs e atividades de MMP-2 e MMP-9 foram estatisticamente maiores no GA em comparação ao GC (p<0,05). Os GL, GH e GHL exibiram menores atividades das isoformas ativas da MMP-2 e MMP-9 em comparação ao GA (p<0,05). Com base nos resultados, concluiu-se que o LBP e HSAPM demonstraram efeitos anti-inflamatórios e protetores sobre as estruturas articulares. A terapia com uso simultâneo do LBP e HSAPM não foi superior aos respectivos tratamentos isolados / Abstract: Temporomandibular disorder (TMD) is a collective term that encompasses several clinical signs and symptoms related to mastigation muscles, temporomandibular joint (TMJ) and its associated structures. The main complaints reported are noise and pain at TMJ region showing higher prevalence in young adults, especially women. The intra-articular inflammation is considered one of the main sources of pain in the development of TMD. The inflammatory process may be located in the synovial membrane, articular capsule or retrodiskal tissues, and the presence of degenerative joint changes is called arthritis. Currently, Low-level laser (LLL) and high molecular weight sodium hyaluronate (HMWSH) have been used for treating TMJ disorders and promising clinical results have been reported. Experimental studies, from the perspective of cellular and molecular biology, are needed for better understanding of their respective biological effects allowing the development of secure clinical protocols. Thus, the aim of this study was to characterize the morphological and biochemical action of the therapy with LLL and HMWSH on a TMJ with induced arthritis. 48 male rats were divided into the following groups: GA, animals with arthritis induced by an intra-articular complete Freund's adjuvant (CFA) injection; GL, animals with arthritis treated with LLL; GH, animals with arthritis treated with HMWSH; and GHL, animals with arthritis treated with LLL and HMWSH. All experiments occurred in the left TMJ. The right TMJs in GA were used as controls (GC). Morphological analysis were performed using slices stained with hematoxylin-eosin (HE), toluidine blue and Picrosirius. Histomorphometric analysis and quantification of birefringence collagen fibers (polarization microscopy) were performed on the articular disc. The biochemical analysis of the TMJ tissues were performed by dosing sulfated glycosaminoglycans (GAGs) and zymography to assess the matrix metalloproteinases (MMP) 2 and 9. Data were statistically analyzed using the one-way ANOVA test with the Tukey's post hoc test and Kruskal-Wallis test followed by the Dunn's post hoc test. GA exhibited marked morphological changes in the components of the TMJ such as thickness of the joint disk; hyperplasia of the synovial membrane and pannus formation; bone resorption of mandibular fossa; flattening of the mandibular condyle and the presence of intense inflammatory infiltrate of mononuclear cells in the subsynovial tissue. The polarization microscopy showed lower birefringence of collagen fibers, indicating a high degree of collagen fibers disorganization. The GL, GH and GHL showed narrower articular disc and higher birefringence of collagen fibers compared to GA (p<0,05). In biochemical analysis, it was demonstrated that the concentration of GAGs and MMP-2 and MMP-9 activities were statistically higher in GA compared to GC (p<0,05). The GL, GH and GHL showed lower activity of the active isoform of MMP-2 and MMP-9 in comparison to GA (p<0,05). Based on the results, it is concluded that The LLL and HMWSH demonstrated anti-inflammatory and protective effects on joint structures. Therapy with concurrent use of LLL and HMWSH was not superior to the respective single treatments / Mestrado / Anatomia / Mestre em Biologia Celular e Estrutural

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-06-21T15:40:31Z No. of bitstreams: 1 Ana Carolina Araruna Alves.pdf: 1155545 bytes, checksum: 5e9fda24285778105d5ac0d8276f9036 (MD5) / Made available in DSpace on 2018-06-21T15:40:31Z (GMT). No. of bitstreams: 1 Ana Carolina Araruna Alves.pdf: 1155545 bytes, checksum: 5e9fda24285778105d5ac0d8276f9036 (MD5) Previous issue date: 2016-03-29 / Rheumatoid Arthritis (RA) treatment in the last decades has evolved medications with cytokine inhibitors, which though they are today considered the gold standard in RA treatment, still do not guarantee complete remission from the disease or from hyperalgesia, and it is know that the Photobiostimulation (PBM) is also capable of acting on the expression of pro-inflammatory cytokines, being in this way an alternative treatment for RA. This research had as its objective the analysis and comparison of the effects of PBM in the acute phase of experimental RA in terms of nociception, of the number of inflammatory cells (neutrophils, macrophages, lymphocytes), and of the protein expression of inflammatory mediators (TNF-α, IL-6, IL-10), in the lavage and joint cartilage of rats. 49 male Wistar rats were used, with an approximate age of 90 days and a body weight varying from 250 to 300g. The animals were randomly distributed in 3 groups, with 21 animals in each experimental group (Rheumatoid arthritis group – RA) and the group treated with PBM (RA-LLLT), and with 7 animals in the control group. Each group was arrranged in three distinct experimental periods according to the time of euthanasia (6 hours, 24 hours, and 48 hours). For the reproduction of the lesion the animals were submitted to two inductions: the first consisted in a subcutaneous infiltration in the dorsal of each animal (in the RA and RA-LLLT groups) using 500 µg of mBSA diluted in a solution of 100 µL of complete Adjuvant de Freund (CFA), and 100 µL of PBS, with this procedure being repeated weekly for 21 days. On the 28th day, an intrajoint induction was carried out with 10 µg of mBSA diluted in 10µL of PBS, in the joint space of the right hind paw of each animal. After the joint induction, the treatment on the RA-LLLT group began, using a DMC® brand Photon Laser III, with a wave length of λ 808 nm, active medium of Gallium Arsenide, and Aluminium (AsGaAI), with a potency of 50 mW (potency density of 1,78 W/cm2) and area of the beam 0,028cm2. The final dose was of 2J, the density of energy of 71,2 J/cm2, and time of 40s by point. At the end of each test period (6 hours, 24 hours, and 48 hours) the animals were submitted to an evaluation of their nociception, followed by the extraction of joint lavage and joint cartilage, which were sent for analysis of the total count and differential cells, and for protein expression of the inflammatory mediators described. The results demonstrate biomodulation in the expression of neutrophils and macrophages amongst the control group and RA, as well as in the cytokines IL-6 and IL-10, contributing daily to the attenuation of hyperalgesia by the PBM. / O tratamento para Artrite Reumatoide (AR) com inibidores de citocinas tem sido considerado padrão-ouro nas últimas décadas embora ainda não garantam a remissão completa da doença ou da hiperalgesia, sabe-se que a Laserterapia de Baixa Intensidade (LBI) também é capaz de atuar na expressão das citocinas pró-inflamatórias, podendo ser assim, uma alternativa de tratamento para a AR. Este trabalho teve como objetivo analisar os efeitos da LBI na fase aguda de AR experimental sobre a nocicepção, sobre o número de células inflamatórias (neutrófilos, macrófagos, e linfócitos), e sobre a expressão proteica de mediadores inflamatórios (TNF-α, IL-6, IL-10) no lavado e cartilagem articular de ratos. Foram utilizados 49 ratos Wistar, machos, com idade aproximada de 90 dias e peso corporal variando de 250 a 300 g. Os animais foram distribuídos aleatoriamente em 3 grupos, com 21 animais em cada grupo experimental (grupo Artrite Reumatoide - RA e o grupo tratado com laser AR-LBI), e 7 animais no grupo controle. Cada grupo foi composto por 3 tempos experimentais distintos de acordo com o tempo da eutanásia (6 horas, 24 horas e 48 horas). Para a reprodução da lesão os animais foram submetidos a duas induções: a primeira consistiu em uma infiltração subcutânea no dorso de cada animal (nos grupos AR e AR-LBI) utilizando-se 500 µg de mBSA diluído em uma solução de 100 µL de Adjuvante completo de Freund (CFA), e 100µL de PBS, esse procedimento foi repetido semanalmente por 21 dias. No 28º dia, foi realizada uma indução intra-articular com 10 µg de mBSA diluído em 10µL PBS, no espaço articular da pata direita traseira de cada animal. Após a indução articular, deu-se início ao tratamento no grupo AR-LBI, por meio do laser da marca DMC® modelo Photon Laser III, com comprimento de onda de λ 808 nm, meio ativo de Arsenieto de Gálio e Alumínio (AsGaAI), com potência de 50 mW (densidade de potência de 1,78 W/cm2), área do feixe de 0,028cm2 e aplicação sob a forma de dois pontos pelo método transcutâneo nos compartimentos medial e lateral da articulação, dose final foi de 2J, densidade de energia de 71,2 J/cm2, e tempo 40s, por ponto. Ao final de cada período experimental (6 horas, 24 horas e 48 horas) os animais foram submetidos à avaliação da nocicepção, seguido de extração do lavado articular e da cartilagem articular, que foram encaminhados às análises de contagem total e diferencial de células, e da expressão proteica dos mediadores inflamatórios descritos. Os resultados demonstram biomodulação da LBI principalmente na expressão de neutrófilos e macrófagos entre os grupos controle e AR, bem como nas citocinas IL-6 e IL-10, contribuindo diretamente para a atenuação da hiperalgesia.