The management of parallel and series resonance conditions is important for ensuring that harmonic levels are managed on utility networks, and that shunt compensators are able to operate without constraints for various network conditions (states). For these and similar problems, harmonic impedance assessment of the ac network is required for the design of ac filter or shunt capacitor bank installations. This is particularly important for large installations connected to HV or EHV systems, because resonances at these voltage levels tend to be highly un-damped resulting in potentially damaging voltage and current amplification. The objective of this dissertation was to develop and demonstrate a design methodology which makes use of network impedance assessment methods to provide robust harmonic integration of large shunt compensators into a transmission and HVDC systems. The design methodology has two aspects. The first part considers network modeling, evaluation of different models and simulation of harmonic impedance. In the second part, methods of analyzing and assessing the simulated harmonic impedance are developed. A detailed step-by-step approach was taken in the development of the design methodology. The methodology was documented as a guideline and accompanied by the development of an Excel tool that can be used to assess the simulated harmonic impedance. The Excel tool permits a systematic assessment of the simulated network impedance where shunt compensators are integrated into transmission systems. The tool also ensures that the design of transmission and HVDC ac shunt compensation is optimally robust in terms of harmonic resonances. The theoretical and computational review has been tested and demonstrated on the existing Eskom Transmission system through several case studies. The results have shown the merits of the design methodology. / Thesis (M.Sc.Eng.)-University of KwaZulu-Natal, Durban, 2013.

Τα τελευταία χρόνια έχει αρχίσει να διαδίδεται με γρήγορους ρυθμούς η μέθοδος μεταφοράς ισχύος μέσω συνεχούς ρεύματος. Προς αυτή την κατεύθυνση ώθηση έδωσε η ανάπτυξη νέων ημιαγωγικών διακοπτικών στοιχείων οδηγώντας σε περεταίρω ανάπτυξη και χρήση των συστημάτων μεταφοράς με συνεχές ρεύμα. Σε αυτή τη διπλωματική εργασία μελετάται ένα σύστημα μεταφοράς ισχύος με διασύνδεση συνεχούς ρεύματος (HVDC), που συνδέεται ανάμεσα σε δυο εναλλασσόμενα ηλεκτρικά δίκτυα με και χωρίς φορτίο. Την διασύνδεση συνεχούς ρέματος πραγματοποιούν δυο back-to-back AC/DC μετατροπείς VSC, που αναλαμβάνουν τους ρόλους του ανορθωτή και του αντίστροφα ισχύος. Οι μετατροπείς χρησιμοποιούν την διαμόρφωση πλάτους παλμού PWM. Αρχικά μελετάται θεωρητικά το μοντέλο των μετατροπέων και του back-to-back HVDC συστήματος και στην συνέχεια σχεδιάζεται και αναλύεται η λειτουργία του ανάμεσα σε δυο δίκτυα εναλλασσομένου ρεύματος με ή χωρίς την ταυτόχρονη παρουσία φορτίου. Τέλος προσομοιώνεται το σύστημα μέσω του λογισμικού Matlab και συγκεκριμένα της εφαρμογής Simulink για την εξαγωγή συμπερασμάτων. / In the past few years the method of power transmission by means of direct current has expanded rapidly. To this direction a push forward has been given by the development of new semi-conductive switching valves leading to a further development of transmission systems by direct current. In this thesis what is considered is a power transmission system via direct current HVDC connected between two AC electric networks with or without load. The direct current connection is achieved through back-to-back AC/DC converters VSC which undertake the role of rectifier and that of inverter of power. The converters use the Pulse Width Modulation (PWM). At first the converter model and the back-to-back HVDC system is theoretically approached and in the process what is designed and analyzed is its function between two networks of AC current with or without the simultaneous presence of load. Finally the system is simulated through software Matlab and specifically the application of simulink in order to draw conclusions.

Thesis (MScEng)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The worldwide increase in the popularity of high voltage direct current (HVDC) power transmission application has led to questions regarding the performance of high voltage alternating current (HVAC) insulators when energized under HVDC excitation. These questions have led researchers conduct numerous research projects worldwide. A particular question NamPower (the power utility in Namibia) has faced is: how do these insulators perform and age when energized under HVDC excitation in heavily polluted environments? This question was only partly answered by some insulator ageing tests conducted under laboratory conditions for HVDC excitation. However, the natural ageing tests on insulators, which are preferred, have to date been confined predominantly to HVAC excitation voltages. Thus, this research was initiated to investigate the natural ageing performance of insulators under both HVAC and HVDC excitations, when subjected to harsh marine pollution environments. This research project involved performance and ageing tests on three identical sets of line insulators made from different insulator materials, energised under HVAC and both polarities HVDC excitations respectively. The tests were conducted at Koeberg insulator pollution test station (KIPTS), which is a natural marine pollution insulator test station located near Cape Town, along the west coast of South Africa, approximately 50 m from the sea. The set of insulators consisted of EPDM silicone alloy rubber, HTV silicone rubber, RTV silicone rubber coated porcelain, Porcelain and Glass insulators. The HVAC excitation voltage was chosen as 12.7 kV r.m.s. phase-to-ground and it was decided to use a HVDC excitation voltage equal to this value. The research results showed that the insulators made from HTV silicone rubber performed better than the insulators made from EPDM silicone alloy rubber under all excitation voltages. It is also showed that RTV silicone rubber coated porcelain insulators performed better than Glass and Porcelain insulators under all excitation voltages. / AFRIKAANSE OPSOMMING: Die wêreld wye toename in gewildheid van hoë spanning gelyk stroom (HSGS) krag transmisie aplikasie het gelei na vrae oor die effektieweteit van hoë spanning wissel stroom (HSWS) insolators in HSGS aplikasies. Hierdie vrae het gelei na baie navorsings projekte. Een vraag waarmee NamPower (die krag voorsienings maatskapy in Namibia) gekonfronteer was, was hoe gaan die insolators wat onderworpe is aan ’n HSGS toevoer reageer in ’n baie besoedelde omgewing. Hierdie vraag was slegs gedeeltelik beantwoord deur verouderings toetse op insolators wat gedoen is in ’n labaratorium met ’n HSGS toevoer. Inteendeel, die meeste natuurlike verouderings toetse op insolators, soos verkies, is meestal gedoen met ’n HSWS toevoer. Om hierdie rede was hierdie navorsing begin om natuurlike verouderings toetse te doen op insolators onderworpe beide aan HSWS en HSGS toevoere binne ’n marien besoedelde omgewing. Hierdie navorsings projek gaan oor prestering en verouderings toetse op drie, identiese, transmissie lyn insolator stelle, wat onderskeidelik onderworpe was aan HSWS en beide polariteite HSGS toevoere. Die toetse was gedoen by Koeberg insolator besoedeling toets stasie (KIBTS) wat naby Kaapstad geleë is langs die weskus van Suid Africa omtrent 50 m van die see. ’n Stel toets insolators bestaan uit EPDM silikon allooi rubber, HTV silikon rubber, RTV silikon rubber bedekte porselein, Porselein en Glas insolators. Die HSWS waarde waarmee die insolators getoets was, was 12.7 kV w.g.k., fase-na-grond, en dit was besluit om ’n HSGS waarde gelyk aan hierdie spannings waarde te gebruik. Die navorsings resultate wys dat insolators wat gemaak is met HTV silikon rubber presteer beter as insolators wat met EPDM silikon allooi rubber gemaak is onder al die verskillende toevoere. Dit wys ook dat RTV silikon rubber bedekte porselein presteer beter as Porselein en Glas insolators onder al die verskillende toevoere.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Revestimentos produzidos a partir de ligas de Zn-Co são comumente utilizados em indústrias (aeronáutica, de isoladores elétricos e automobilística, por exemplo) devido à sua ótima resistência à corrosão, principalmente quando comparados aos tradicionais revestimentos de Zn puro. Na co-deposição de zinco com metais, como o ferro, cobalto e níquel, ocorre o que se chama de deposição anômala, onde o metal menos nobre (zinco) é preferencialmente depositado, independente do modo de corrente aplicada (contínua ou pulsada). Recentemente, diversos trabalhos relacionam a produção de eletrodepósitos de liga Zn-Co a partir de banhos ambientalmente não agressivos, a fim de substituir os banhos alcalinos extremamente tóxicos, a base de cianeto. Na presente dissertação foram produzidos revestimentos de ligas de Zn-Co sobre substrato de aço carbono, empregando corrente contínua ou corrente pulsada simples, a partir de banhos contendo diferentes concentrações de Co2+ (0,05 mol/L e 0,10mol/L), 0,05 mol/l de Zn2+ e citrato de sódio (0,10 mol/L) como agente complexante, sob condições agitadas. Quatro diferentes valores de densidade de corrente (10 A/m2, 20 A/m2, 40 A/m2 e 80 A/m2) e de frequência de pulso (100 Hz, 500 Hz, 1000 Hz, 2000 Hz) foram aplicados para a produção da liga a partir dos dois banhos, tendo como objetivo avaliar a influência dos parâmetros de deposição(concentração de Co (II), densidade de corrente aplicada e, no caso de deposição por corrente pulsada simples, também da frequência de pulso), nas variáveis eficiência de corrente catódica, composição da liga, densidade de corrente de corrosão, microestrutura e morfologia dos depósitos de liga Zn-Co. As cores das camadas obtidas variaram do cinza claro ao escuro, quase sempre sem brilho, independente do modo de corrente empregado. Foi verificado que o processo normal de eletrodeposição foi prevalente na produção de revestimentos por corrente contínua, enquanto que apenas deposição anômala foi observada quando do uso de corrente pulsada. A maior eficiência de corrente catódica (60%) foi obtida, para corrente contínua, nas condições de menor concentração de Co2+ (0,05 mol/L) e maior densidade de corrente (80 A/m2). Nestas mesmas condições foi determinada uma eficiência de corrente catódica de 98% para corrente pulsada simples na freqüência de 2000 Hz. Maiores teores do metal mais nobre (cobalto) foram alcançados em maiores densidades de corrente para todas as condições empregadas. Os revestimentos assim obtidos apresentavam os menores valores de tamanho de grão, para cada uma das soluções estudadas. Os demais parâmetros estudados também influenciaram na granulometria e na morfologia das ligas obtidas. Revestimentos com melhor resistência à corrosão, contendo teores de cobalto entre aproximadamente 8 e 10% m/m, foram produzidos a partir do banho com maior concentração de Co2+, sob corrente pulsada simples / Zn-Co alloys coatings are commonly used in the industry (aerospace, automotive and electrical insulators, for example) due to their great corrosion resistance, mainly when compared to pure zinc coatings. In the zinc co-deposition with different metals, such as iron, cobalt or nickel, it is observed an anomalous deposition, in which the less noble metal (zinc) is preferably deposited, regardless the current type applied (direct or pulsed). Recently, several studies relate the production of electrodeposited Zn-Co alloys from environmentally non-aggressive baths to substitute the extremely toxic cyanide-based alkaline baths. In this dissertation, Zn-Co alloy coatings were produced on carbon steel substrate using direct or simple pulsed currents, from baths with different Co2+ concentrations (0.05 mol/L and 0.10 mol/L), 0.10 mol/L of Zn2+and sodium citrate (0.10 mol/L) as a complexing agent, under stirring. Four different current densities values (10 A/m2, 20 A/m2, 40 A/m2 and 80 A/m2) and four different pulse frequencies values (100 Hz, 500 Hz, 1000 Hz and 2000 Hz) were applied in order to obtain the alloys from both baths, aiming to assess the influence of the deposition parameters (Co (II) concentration, current density applied, and also pulse frequency, for the simple pulsed current process) in the variables cathodic current efficiency, alloy composition, current corrosion density, and Zn-Co alloy deposit microstructure and morphology. The obtained layers colours varied from light to dark grey, normally dull, regardless the current type used. Normal electrodeposition process was predominant when direct current was used, whereas only anomalous deposition was observed when using pulsed current. The highest cathodic current efficiency (60%) was obtained in direct current for the lowest Co2 + concentration (0.05 mol / L). Under these same conditions it was determined a cathodic current efficiency of 98% for single pulsed current, employing the frequency of 2000 Hz Higher content of the noblest metal (cobalt) were achieved for higher current densities for all conditions studied. These coatings presented the smallest grain sizes, for each of the evaluated solutions. The other studied parameters have also influenced in the granulometry and the morphology of the obtained alloys. Coatings presenting the best corrosion resistance, showing the cobalt content between 8 and 10% m/m, were obtained from the highest Co2+ concentration bath, using simple pulsed current

O transtorno do déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento e sua prevalência na vida adulta é em torno de 2,5%. O tratamento farmacológico, apesar de efetivo, possui importantes limitações, justificando a busca por outras estratégias terapêuticas. A estimulação elétrica transcraniana (EETC) é uma técnica não invasiva de neuroestimulação que tem apresentado resultados promissores em melhorar o desempenho cognitivo em vários distúrbios neuropsiquiátricos, no entanto, poucos estudos avaliaram a sua eficácia e tolerabilidade no TDAH. Foi realizado um ensaio clínico randomizado, duplo-cego e controlado, com estimulação falsa para avaliar a eficácia da EETC nos sintomas de TDAH. Dezessete adultos com TDAH foram randomizados em dois grupos, nove receberam EETC verdadeira e oito, falsa. No grupo da EETC verdadeira foi aplicada estimulação com intensidade de corrente de 2 mA, durante 20 minutos, em cinco dias consecutivos. O ânodo foi posicionado sobre o córtex pré-frontal dorsolateral (CPFDL) direito e o cátodo sobre o CPFDL esquerdo. O grupo controle recebeu estimulação falsa durante o mesmo período. Os sintomas do TDAH foram mensurados por meio da escala Adult ADHD Self-Report Scale (ASRS) e a incapacidade com a escala Sheehan Disability Scale (SDS). As duas escalas foram aplicadas nos seguintes momentos: antes de iniciar (t0) as estimulações, ao final do protocolo (t1) e uma (t2), duas (t3) e quatro semanas (t4) após a intervenção. Observamos redução, estatisticamente significativa, na pontuação das escalas ASRS desatenção (p = 0,02) e SDS (p = 0,04) entre t0 e t1 após a intervenção em comparação ao grupo controle. Na ASRS total também observamos essa tendência, mas não se mostrou estatisticamente significativa (p = 0,07). Ampliando a análise dos dados observamos interação positiva entre tempo e tratamento na pontuação da ASRS total (p = 0,003), ASRS desatenção (p = 0,0001) e SDS (p = 0,001). Os dados deste estudo apontam que a EETC é eficaz para melhorar a atenção em adultos com TDAH. Contudo, mais pesquisas são necessárias para avaliar a eficácia clínica da ETCC nessa população. / Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with 2,5% prevalence in adulthood. Pharmacological treatment, although effective, has important limitations, justifying the search for other therapeutic strategies. Transcranial direct-current stimulation (tDCS) is a non-invasive neurostimulation technique which has show promising results to improve cognitive performance in several neuropsychiatric disorders, nonetheless few studies have evaluated their efficacy and tolerability in ADHD. A randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on ADHD symptoms. in adults with ADHD. Seventeen adults with ADHD were randomized into two groups, nine received active EETC eight, false. In the active group was applied EETC with 2mA current intensity, for 20 minutes, in five consecutive days. Anode was positioned on the right dorsolateral prefrontal cortex (DLPFC) and cathode over the left DLPFC. Control group received false stimulation during the same period. ADHD symptoms were measured using the scale Adult ADHD Self-Report Scale (ASRS) and the disability with Sheehan Disability Scale Scale (SDS). Both scales were applied at the following times: before starting the stimulation, the end of the protocol, and one, two and four weeks after the intervention. Subjects in the active group achieved significant reduction in ASRS inattention (p = 0,02) and SDS (p = 0,04) scores after intervention compared to control group. At ASRS total score was also observed this trend, without statistical significance (p = 0.07). Extending data analysis shows there are positive interaction between time and treatment on ASRS total score (p = 0,003), ASRS inattention (p = 0,0001) and SDS (p = 0,001). These data indicate that tDCS is effective to improving attention in adults with ADHD. However, further research is needed to assess the clinical efficacy of tDCS in this population.

Les réseaux multi-terminaux à courant continu sont une solution efficace pour intégrer l’énergie électrique produite en grande quantité par de grands parcs éoliens offshore. Bien que le recours à la technologie HVDC soit maitrisé pour des applications point-à-point, des verrous technologiques sont encore à lever pour permettre une exploitation sûre d’un réseau à courant continu. La protection est le principal domaine technique pour lequel des progrès sont encore attendu. Des stratégies de protection fiables et assurant le meilleur ratio technico-économique sont à l’étude. Ces travaux de thèse ont pour objectif la mise en œuvre d’une philosophie de protection à sélectivité totale, identique à celle utilisée dans les réseaux de transport traditionnels. Cette étude considère l’utilisation de liaison par câbles uniquement, de convertisseurs VSC-MMC composées de sous-modules en demi-pont et de disjoncteurs hybrides à courant continu. Une association de deux algorithmes de détection de défaut a été proposée. Une étude du temps disponible pour l’élimination du défaut a été menée. Enfin, des simulations numériques avec le logiciel EMTP ont permis d’évaluer la fiabilité de la stratégie de protection. / In a near future, multi-terminal High Voltage Direct Current grids (MT-HVDC grids) appear to be a suitable solution for the integration of power electricity produced by remote offshore windfarms into the AC transmission system. Though the recourse to HVDC point-to-point links is well-known, challenges still remain for a safe operation of HVDC grids. Protection is the main technical field still under study and reliable protection strategies ensuring the best technological and economic ratio are investigated. This thesis focused on a full selective protection philosophy similar to the one applied to AC transmission systems. The consideration of cable links, Half-Bridge VSC-MMC converters and hybrid DC circuit breakers defines the frame of the study. An association of two algorithms for the identification of faults is suggested. The time available for the fault clearing process has been investigated. Simulations performed with EMTP software have been used to evaluate the reliability of the suggested strategy.

Les inductances et interconnexions des composants passifs intégrés pour la téléphonie mobile, sont sujettes à des défaillances dues à l’électromigration et l’auto-échauffement. L’électromigration n’est pas un risque majeur, au regard des grandes dimensions de cuivre de la technologie étudiée et de l’application. L’auto-échauffement est, en revanche, le principal phénomène qui limite le choix des dimensions des inductances et interconnexions lors de leurs conceptions.L’effet Joule pour les interconnexions et les inductances, a été étudié par le biais de caractérisations et de simulations électrothermiques. La méthodologie des plans d’expériences a été utilisée afin de modéliser le comportement électrothermique des inductances et des interconnexions. Un modèle prédictif de l’auto-échauffement en fonction des dimensions et de l’intensité, a été déterminé permettant d’étudier et de déterminer l’influence de chaque facteur dimensionnel, en régime continu. En radiofréquence, une méthodologie de mesure de l’auto-échauffement a été déterminée permettant sa caractérisation sur des composants sur plaquette. Une corrélation entre les régimes continus et alternatifs ne donnant pas de résultat concluant, une méthodologie de couplage faible, entre un simulateur électromagnétique et électrothermique a été effectuée, permettant la simulation du phénomène d’auto-échauffement sous contrainte radiofréquentielle. / Electrothermal and electromigration failure are likely to occur on copper inductor and interconnection in integrated passive devices for wireless telephony application. Electromigration is not a concern considering the high thickness of the copper and the application but the Joule heating is the main restriction on the dimensions during the component design. Joule heating on interconnections and inductors has been studied by electrothermal characterization and simulation. We have shown that Joule heating depends of several parameters such as material layers parameters and component dimensions. Design of experiments methodology has been used in order to model the inductor and interconnection electrothermal behavior. A self-heating predictive model has been determined allowing the study and the determination of dimensions impact in direct current.In radiofrequency, a self-heating measurement methodology has been determined allowing its characterization at wafer level. A correlation between direct current and radiofrequency is not satisfactory and a weak coupling between an electromagnetic and electrothermal simulator has been performed, providing the self-heating simulation under radiofrequency stress.

O transtorno do déficit de atenção e hiperatividade (TDAH) é um transtorno do neurodesenvolvimento e sua prevalência na vida adulta é em torno de 2,5%. O tratamento farmacológico, apesar de efetivo, possui importantes limitações, justificando a busca por outras estratégias terapêuticas. A estimulação elétrica transcraniana (EETC) é uma técnica não invasiva de neuroestimulação que tem apresentado resultados promissores em melhorar o desempenho cognitivo em vários distúrbios neuropsiquiátricos, no entanto, poucos estudos avaliaram a sua eficácia e tolerabilidade no TDAH. Foi realizado um ensaio clínico randomizado, duplo-cego e controlado, com estimulação falsa para avaliar a eficácia da EETC nos sintomas de TDAH. Dezessete adultos com TDAH foram randomizados em dois grupos, nove receberam EETC verdadeira e oito, falsa. No grupo da EETC verdadeira foi aplicada estimulação com intensidade de corrente de 2 mA, durante 20 minutos, em cinco dias consecutivos. O ânodo foi posicionado sobre o córtex pré-frontal dorsolateral (CPFDL) direito e o cátodo sobre o CPFDL esquerdo. O grupo controle recebeu estimulação falsa durante o mesmo período. Os sintomas do TDAH foram mensurados por meio da escala Adult ADHD Self-Report Scale (ASRS) e a incapacidade com a escala Sheehan Disability Scale (SDS). As duas escalas foram aplicadas nos seguintes momentos: antes de iniciar (t0) as estimulações, ao final do protocolo (t1) e uma (t2), duas (t3) e quatro semanas (t4) após a intervenção. Observamos redução, estatisticamente significativa, na pontuação das escalas ASRS desatenção (p = 0,02) e SDS (p = 0,04) entre t0 e t1 após a intervenção em comparação ao grupo controle. Na ASRS total também observamos essa tendência, mas não se mostrou estatisticamente significativa (p = 0,07). Ampliando a análise dos dados observamos interação positiva entre tempo e tratamento na pontuação da ASRS total (p = 0,003), ASRS desatenção (p = 0,0001) e SDS (p = 0,001). Os dados deste estudo apontam que a EETC é eficaz para melhorar a atenção em adultos com TDAH. Contudo, mais pesquisas são necessárias para avaliar a eficácia clínica da ETCC nessa população. / Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with 2,5% prevalence in adulthood. Pharmacological treatment, although effective, has important limitations, justifying the search for other therapeutic strategies. Transcranial direct-current stimulation (tDCS) is a non-invasive neurostimulation technique which has show promising results to improve cognitive performance in several neuropsychiatric disorders, nonetheless few studies have evaluated their efficacy and tolerability in ADHD. A randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on ADHD symptoms. in adults with ADHD. Seventeen adults with ADHD were randomized into two groups, nine received active EETC eight, false. In the active group was applied EETC with 2mA current intensity, for 20 minutes, in five consecutive days. Anode was positioned on the right dorsolateral prefrontal cortex (DLPFC) and cathode over the left DLPFC. Control group received false stimulation during the same period. ADHD symptoms were measured using the scale Adult ADHD Self-Report Scale (ASRS) and the disability with Sheehan Disability Scale Scale (SDS). Both scales were applied at the following times: before starting the stimulation, the end of the protocol, and one, two and four weeks after the intervention. Subjects in the active group achieved significant reduction in ASRS inattention (p = 0,02) and SDS (p = 0,04) scores after intervention compared to control group. At ASRS total score was also observed this trend, without statistical significance (p = 0.07). Extending data analysis shows there are positive interaction between time and treatment on ASRS total score (p = 0,003), ASRS inattention (p = 0,0001) and SDS (p = 0,001). These data indicate that tDCS is effective to improving attention in adults with ADHD. However, further research is needed to assess the clinical efficacy of tDCS in this population.

Introdução: Os quadros de dores crônicas são prevalentes, relacionados a alterações físicas e psicológicas, que induzem prejuízos na qualidade de vida. Mais especificamente, a dor inflamatória crônica caracteriza-se por desencadear sustentada hiperexcitabilidade de neurônios no corno dorsal da medula espinhal. O processo nociceptivo da dor crônica inflamatória reduz a atividade do sistema melatonérgico que pode estar associada com dessincronização dos ritmos biológicos. Objetivo: Avaliar o uso pré-clínico de novas opções terapêuticas (melatonina e ETCC) para o tratamento de dor inflamatória crônica. Métodos: A inflamação crônica foi induzida por uma injeção de Adjuvante completo de Freund (ACF). No primeiro experimento, os ratos receberam 60 mg/kg de melatonina ou de veículo (1% de álcool em soro fisiológico), por via intraperitoneal, por três dias consecutivos. No segundo experimento, quinze dias após a injeção os animais foram tratados com injeção intraperitoneal (ip) de dexametasona (0,25 mg/kg) ou seu veículo (solução salina) por 8 dias. No terceiro experimento, os animais foram tratados com dexametasona (0,25 mg/kg) ou seu veículo, melatonina (50 mg/kg) ou seu veículo (8% de etanol em solução salina), e melatonina mais dexametasona ou seus veículos, por 8 dias. No quarto experimento, todos os ratos apresentavam inflamação crônica e foram divididos em dois grupos: estimulação transcraniana por corrente contínua (ETCC) e estimulação sham. Resultados: No primeiro experimento, a administração de melatonina durante 3 dias consecutivos, mostrou um efeito analgésico significativo sobre a dor inflamatória. No segundo experimento, a dexametasona produziu um aumento significativo na latência no teste da placa quente (ANOVA de uma via, P<0,05) e no limiar de retirada no teste de von Frey eletrônico (P <0,005). O grupo dexametasona apresentou aumento dos níveis de BDNF em medula espinhal comparado aos outros grupos (ANOVA de uma via P<0,05). No terceiro experimento, os animais inflamados apresentaram uma desregulação do ritmo de atividade repouso que foi reestabelecido apos o tratamento farmacológico com melatonina que demonstrou ritmo atividade repouso sincronizado. Adicionalmente os animais tratados com dexametasona isolada ou associada a melatonina mostraram inibição acentuada de parâmetros inflamatórios nos achados histológicos, enquanto a melatonina mostrou uma discreta inibição nos mesmos. Ao final do tratamento foi observado um aumento significativo no limiar de retirada da pata no teste de von Frey em grupos tratados (ANOVA de uma via, P<0,05 para todos). No quarto experimento, após oito sessões de 20 minutos de 500 mA de ETCC anódica foi observado efeito antinociceptivo avaliado pelo teste da placa quente imediatamente (P= 0,04) e 24 horas após a última sessão de ETCC (P=0,006). Foi observado também, um aumento de latência de retirada no teste de Von Frey, 24 horas após a última sessão (P= 0,01). Conclusão: Nossos achados confirmam as propriedades antinociceptiva e antiinflamatórias da dexametasona; e podemos sugerir uma relação entre a analgesia e o aumento nos níveis de BDNF em espinhal medula observados apos o tratamento. Por outro lado, a melatonina demonstrou fortes efeitos cronobiótico e antinociceptivo, associados a discreto efeito anti-inflamatório. A associação dexametasona+melatonina não potencializou seus efeitos. Já, a ETCC mostrou-se eficaz induzindo efeito analgésico de longa duração no modelo em estudo. Sendo assim, as propostas de novas terapêuticas abordadas nesta tese parecem ser interessantes opções como adjuvante no tratamento da dor crônica. / Background: Chronic pain is related to physical and psychological changes that induce losses in quality of life. More specifically, chronic pain is characterized by trigger sustained hyperexcitability of neurons in the dorsal horn of the spinal cord. The nociceptive process of chronic inflammatory pain reduces the activity of melatonergic system that can be associated with desynchronization of biological rhythms. Objective: Evaluate the pre-clinical use of new therapeutic options (melatonin and tDCS) for the treatment of chronic inflammatory pain. Methods: Chronic inflammation was induced by injection of complete Freund's adjuvant (CFA). In the first experiment, rats received 60 mg/kg of melatonin or vehicle (1% ethanol in saline) intraperitoneally for three consecutive days.In the second experiment, fifteendays after the injection the animals were treated with intraperitoneal (ip) injection of dexamethasone (0.25 mg/kg) or its vehicle (saline) for 8 days. In the third experiment, animals were treated with dexamethasone (0.25 mg/kg) or its vehicle, melatonin (50 mg/kg) or its vehicle (8% ethanol in saline), and melatonin plus dexamethasone or its vehicle for 8 days. In the fourth experiment, all rats had chronic inflammation and were divided into two groups: transcranial direct current stimulation (tDCS) and sham stimulation. Results: In the first experiment, administration of melatonin for 3 consecutive days showed a significant analgesic effect on inflammatory pain. In the second experiment, dexamethasone produced a significant increase in latency in hot plate test (one-way ANOVA, P<0.05) and in withdrawal threshold in the electronic von Frey test (P<0.005). The dexamethasone group had increased levels of BDNF in the spinal cord when compared to the other groups (one-way ANOVA P<0.05). In the third experiment, the inflamed animals showed a dysregulation of the rest-activity rhythm that was restored after pharmacological treatment with melatonin. Additionally, the animals treated with dexamethasone alone or associated with melatonin showed marked inhibition of inflammatory parameters in histological findings, while melatonin showed a slight inhibition in them. At the end of treatment there was a significant increase in paw withdrawal threshold to von Frey test in treated groups (one-way ANOVA, P<0.05 for all). In the fourth experiment, after eight 20-minute sessions of 500 mA of anodal tDCS, it was observed an antinociceptive effect assessed by the hot plate test immediately (P = 0.04) and 24 hours after the last session of tDCS (P = 0.006). It was also observed an increase in withdrawal latency in the von Frey test, 24 hours after the last session (P= 0.01). Conclusion: Our findings confirm the antinociceptive and anti-inflammatory properties of dexamethasone, and we can suggest a relationship between analgesia and increased levels of BDNF in spinal cord observed after treatment. Furthermore, melatonin has demonstrated strong chronobiotic and antinociceptive effects associated with mild anti- inflammatory effect. Dexametasone plus melatonin didn’t potentiate its effects. The tDCS was an effective analgesic inducing long-lasting effect. Therefore, proposals for new therapies discussed in this thesis seem to be interesting choices as an adjunct in the treatment of chronic pain.

Introdução: Estimulação transcraniana com corrente contínua (ETCC) é um método não invasivo de estimulação cerebral que modifica o potencial de repouso da membrana neuronal através de uma corrente elétrica de baixa intensidade. Trata-se de uma técnica neuromodulatória aplicável ao contexto terapêutico de disfunções do sistema nervoso implicados na fisiopatologia da dor e transtornos neuropsiquiátricos, com baixo custo, mínimos efeitos adversos e fácil aplicação. A ETCC tem se mostrado eficaz no tratamento de dores crônicas incluindo a fibromialgia (FM) em curto prazo. Seu uso se sustenta na melhor compreensão dos mecanismos fisiopatológicos dessa síndrome, os quais incluem processos de desinibição em nível cortical e infracortical, demonstrado por medidas neurofisiológicas como facilitação e desinibição, assim como redução da potência dos sistemas modulatórios descendentes da dor, além de alterações nas vias nociceptivas periféricas, como as fibras nervosas finas. No entanto, essa alteração isolada não foi previamente associada à disfunção no sistema de modulação descendente da dor (SMDD), observado na FM. As áreas de aplicação da ETCC dependem do objetivo terapêutico. O córtex motor primário (M1) é o alvo mais estudado e com maior contingente de evidências para o tratamento da dor e reabilitação motora, enquanto o córtex pré-frontal dorsolateral esquerdo (DLPFC) tem sido eficaz na depressão e melhora dos componentes psicoafetivos dos pacientes com dor crônica. Seu principal limitador prático é a necessidade de ir ao centro de atendimento durante dias consecutivos, pois o efeito terapêutico sustentado da ETCC necessita repetição das sessões Objetivos: Esta tese está constituída por dois estudos. O primeiro objetiva examinar se a disfunção de fibras finas que ocorre em pacientes com FM está ligada a um mau funcionamento do sistema modulador descendente da dor. No segundo, o objetivo é avaliar a eficácia do uso em longo prazo da ETCC em nível domiciliar na FM, com o objetivo de facilitar o uso e permitir a disponibilização desta técnica a pacientes do Sistema Único de Saúde. Estudo I: No primeiro estudo avaliamos se a disfunção de fibras nervosas finas periféricas está ligada a um mau funcionamento do sistema modulador descendente da dor (SMD) na FM. Métodos: Foi realizado um estudo exploratório no qual 41 mulheres com FM e 28 voluntárias saudáveis foram submetidas a testes psicofísicos que avaliaram a função de fibras sensitivas envolvidas na nocicepção. O teste quantitativo sensorial (QST) foi utilizado para medir o limiar perceptivo térmico (HTT), o limiar de dor térmica (HPT) e o limiar de tolerância à dor térmica (HPTo), bem como avaliar a mudança na Escala Numérica de Dor (NPS0-10) durante uma tarefa de modulação da dor condicionada (CPM-task). A algometria foi utilizada para determinar o limiar de pressão de dor (PPT). Escalas para avaliação de catastrofização, ansiedade, depressão e distúrbios do sono também foram aplicadas. O fator neurotrófico derivado do cérebro (BDNF) foi medido como um marcador de neuroplasticidade. Realizamos modelos de regressão linear multivariada por grupo (saudáveis e FM) para estudar a relação entre a função do SMD e sua relação com as medidas psicofísicas. Resultados: As amostras diferiram em seu perfil psicológico, e nas medidas psicofísicas, o grupo e pacientes com FM apresentou menor sensibilidade e limiares de dor. Na FM, mas não nos saudáveis, os modelos de regressão revelaram que o HTT estava relacionado ao BDNF e ao CPM-Task (Hotelling's Trace = 1,80, P<0,001, poder=0,94, R2=0,64). HTT foi correlacionado positivamente com a CPM-task (B = 0,98, P= 0,004, Partial-ƞ2=0,25), e ao HPT (B=1,61, P=0,008, parcial -ƞ2= 0,21). No entanto PPT não foi correlacionado com o HTT. Na FM a relação do BDNF com CPM-Task teve uma relação negativa (B=-0,04, P=0,043, parcial-ƞ2=0,12) e a HPT foi diretamente proporcional (B= - 0,08, P=0,03, parcial-ƞ2 = 0,14). O BDNF não influenciou no modelo. E os efeitos adversos relatados foram maiores no grupo ativo (17,8%) em comparação com o grupo sham (6,6%). Conclusão: A disfunção sensorial periférica está associada positivamente à disfunção do sistema modulatório descendente da dor e aos níveis séricos de BDNF na FM, o que não ocorre em indivíduos saudáveis. Estudo II: O segundo estudo teve como objetivo avaliar a eficácia do uso domiciliar de 60 sessões da ETCC-ativa e ETCC-simulada aplicadas sobre a área DLPFC esquerda, nas pacientes com diagnóstico de FM. Métodos: Foi realizado um ensaio clínico randomizado, duplo cego, em paralelo, controlado com ETCC-simulada em 20 mulheres com diagnóstico de fibromialgia. A estimulação foi realizada durante cinco dias consecutivos na semana, durante 30 min, com a intensidade de 2 mA, por 12 semanas, totalizando 60 sessões. As pacientes receberam treinamento para uso do equipamento especialmente desenvolvido para uso domiciliar e mantinham contato com o pesquisador responsável por meio de mensagem de texto diariamente. Os efeitos foram medidos por meio da escala visual de dor (EAV) durante o curso de 12 semanas de tratamento, bem como o uso de analgésicos e possíveis eventos adversos, diariamente. Foram avaliados os níveis de depressão, catastrofismo e capacidade funcional para tarefas diárias, QST para verificar limiar de dor e tolerância ao calor, PPT e dosagem dos níveis séricos de BDNF no início, após 30 sessões e no final do tratamento. Um modelo linear misto com efeitos fixos foi usado para comparar mudanças nos escores de dor na EAV ao longo do tratamento. Resultados: A ETCC ativa domiciliar reduziu os escores de dor pela EAV (p<0.001) quando comparado ao sham, com uma redução média de dor de 64% (p<0.001). Além disso, ETCC ativa reduziu significativamente a incapacidade relacionada a dor [B-PCP:S escore total (p=0.023);-ƞ2=0.61]. Também reduziu os escores nas medidas clínicas de depressão, catastrofismo e qualidade do sono [BDI-II, PCS e PSQI (p<0.05)]. No entanto, ETCC ativa aumentou os escores na algometria (PPT) e tolerância térmica (HPTo) (p<0.01). O BDNF não influenciou no modelo. Os efeitos adversos relatados foram maiores no grupo ativo (17,8%) em comparação com o grupo sham (6,6%). Conclusão: A ETCC para uso domiciliar mostrou-se segura e eficaz na redução da dor, incapacidade relacionada a dor, sintomas depressivos e catastróficos e redução do uso de analgésicos. O conjunto de dados desta tese sugere que em pacientes fibromiálgicas, o nível de disfunção do sistema modulador descendente da dor está relacionado ao nível de disfunção de fibras nervosas finas periféricas envolvidas na nocicepção. Além disso, a ETCC de longo prazo em fibromiálgicas foi eficaz na melhora dos sintomas disfuncionais relacionados à dor crônica e se mostrou adequada para uso domiciliar. / Introduction: Transcranial direct current stimulation (tDCS) is a noninvasive method of brain stimulation that modifies the resting potential of the neuronal membrane through a low intensity electrical current. It is a neuromodulatory technique to the therapeutic context of dysfunctions of the nervous system implicit in physiotherapy and neuropsychological disorders, with low cost, adverse effects and easy application. tDCS has been effective without a chronic fight process, including fibromyalgia (FM), in which the processes of disinhibition are cortical and infracortical, demonstrated by neurophysiological as intracortical facilitation and desinhibition, as well as reduction of the power of the systems descending pain modulators. In addition, studies have shown a severity of inhibition of central positive correlation with BDNF (Brain Derived Neurotrophic Factor) levels and seems to have some relation to the peripheral nociceptive pathways, as the areas of application of the stimulation depend on the primary motor cortex (M1) is the most studied target and the largest contingent of selection for the treatment of pain and motor reaction, while the dorsolateral prefrontal cortex (DLPFC) was effective in the treatment of depression and psychoaffective components in cases of patients with the chronic condition. Although tDCS has been successful in treating FM, its main limiter is a need for the service center for consecutive days as it has cumulative effect. In fact, the erasure of the sessions guaranteed the therapeutic effect of the ETCC. The application of measures on consecutive days motivated the study of its value when applied at the household level, in order to allow the large-scale treatment technique to be adopted in the Unified Health System. This is proved by two studies. The first objective is to examine whether a fine-fiber dysfunction that occurs in patients with FM is linked to an operation of the pain-modulating system. Neuropathy of long nerve fibers has been implicated by a descriptor of pain, neurophysiological and psychophysiological neurophysiology, as well as skin biopsy studies. However, this comparison was not associated with dysfunction in the descending pain system (DPMS) not on FM. Objective did the study explore the association of dysfunction of small fibers with the DPMS and other substitutes for nociceptive changes in FM. In the second, the term is a measure of long-term use of ETCC at household level in FM Study I: In this first study evaluating the presence of nerve and peripheral fiber failure, it is linked to the functioning of the descending pain modulator system (DPMS) in FM Methods: It was performed an exploratory study with 41 FM women and 28 healthy volunteers whose were evaluated in psychophysical tests that evaluated a function of sensory fibers involved in nociception. The quantitative sensory test (QST) was used to measure the Heat thermal threshold (HTT), the heat pain threshold (HPT) and the thermal pain tolerance (HPTo), as well as the numerical scale of pain (NPS0 -10 ) over a task of modulation of conditioned pain (CPM-task). Algometry was used to determine the pain pressure threshold (PPT). Scales for evaluation of catastrophic, anxiety, depression and sleep disorders were also applied. Brain-derived neurotrophic factor (BDNF) was measured as a marker of neuroplasticity. Multivariate linear regression models by group (health and FM) for a relationship between a descending modulatory system function and its relationship with psychophysical measures. Results: The samples differed in their psychological profile, and in the psychophysical measures, the group and the patients with FM had lower sensitivity and pain thresholds. At FM, regression models revealed that HTT was related to BDNF and CPM-Task (Hotelling's Trace = 1.80, P <0.001, power = 0.94, R2 = 0.64). HTT was positively correlated with a CPM task (B = 0.98, P = 0.004, partial-ƞ2 = 0.25), and HPT (B = 1.61, P = 0.008, partial -ƞ2 = 0.21) . However PPT was not correlated with HTT. In FM, the relationship of BDNF with CPM, a negative relation was found (B = -0.04, P = 0.043, partial- = 2 = 0.12) and HPT was proportionally (B = -0.08, P = 0.03, partial-ƞ2 = 0.14). BDNF did not influence the model. And the adverse effects reported were higher in the active group (17.8%) compared to the sham group (6.6%). Conclusion: Peripheral sensory dysfunction is positively associated with the modulating dysfunction of BDNF levels in FM, which does not occur in isolated individuals. Study II: The second study had the purpose of evaluating the home use of 60 sessions of atDCS and s-tDCS on a left DLPFC area in patients with FM. Methods: A randomized, double-blind, parallel-sham controlled study in 20 women with FM. Stimulation was performed for five consecutive days in the week for 30 min at the intensity of 2 mA for 12 weeks, totaling 60 sessions. Patients were trained to use equipment specially designed for home use and maintained contact with the researcher responsible through daily text message. The effects were measured through visual pain scale (VAS) daily during the course of 12 weeks of treatment, as well as the use of analgesics and possible adverse events daily. The levels of depression, catastrophism and disability for daily tasks were assessed. The QST was used to check pain threshold and tolerance to heat, an algometry was used to check pressure pain threshold (PPT) and blood collection was performed to evaluate serum BDNF levels at baseline, after 30 sessions and at the end of treatment. A Mixed Linear Model with fixed effects was used to compare changes in pain scores in VAS throughout the treatment. Results: Home-based tDCS reduced dairy pain VAS scores (p<0.001), with cumulative mean pain drop of 64% (p<0.001). Furthermore, active home-based tDCS reduced significantly disability due to pain [B-PCP:S total scores (p=0.023; partial-ƞ2=0.61]. And also reduced scores in clinical measures like depression scores, catastrophizing pain scores and sleep quality scores [BDI-II and PCS (p<0.05), PSQI (p<0.05)]. However, active homebased tDCS enhance scores in algometry (PPT) and heat pain tolerance (HPTo) (p<0.01). Conclusion: Home-based anodal tDCS applied over the DLPFC in FM had a baseline neuroplasticity-dependent reduction effect on pain. In addition, it improved the disability due to pain, depressive symptoms and pain catastrophizing. It reduced the analgesic use and increased pressure and heat pain tolerance.