Introdução: o desenvolvimento de uma vacina contra a esquistossomose será um importante avanço no controle desta doença crônica e muitas vezes debilitante, afetando milhões de pessoas em todo o mundo. Neste trabalho, descrevemos o uso da subunidade B da toxina colérica (CTB) geneticamente fusionada com Sm14 - uma proteína ligadora de ácidos graxos de Schistosoma mansoni - como uma tentativa de desenvolver uma vacina antiesquistossomose. Métodos: proteínas recombinantes foram expressas em um sistema procariótico, purificadas por diferentes métodos cromatográficos e caracterizadas tanto por métodos imunoquímicos como por métodos espectroscópicos. Experimentos de imunização foram realizados em camundongos fêmeas, da linhagem BALB/c e a eficácia da vacina determinada através da análise da carga parasitária após o desafio com cercárias de S. mansoni e através da análise histopatológica das reações granulomatosas ao redor dos ovos aprisionados no tecido hepático dos camundongos. Resultados: a administração subcutânea de Sm14 reduziu em 27% a carga parasitária nos animais vacinados. Por outro lado, a vacinação intranasal apenas demonstrou uma redução estatisticamente significativa quando CTB esteve presente na formulação. Além disso, a co-administração de CTB e Sm14 reduziu em média 30% a área das lesões granulomatosas hepáticas. Conclusão: o uso de CTB demonstrou ser um importante adjuvante de mucosas; contudo, quando utilizada juntamente com a proteína Sm14, esta molécula não resultou em níveis satisfatórios de redução parasitária em um modelo murino para infecção esquistossomótica. / Introduction: developing a vaccine against schistosomiasis would be an important advance on the control of this chronic and debilitating disease which afflicts millions of people worldwide. Herein we describe the use of the non-toxic B subunit of cholera toxin (CTB) genetically fused to Sm14 - a fatty-acid binding protein from Schistosoma mansoni - as an attempt to the development of an antischistosomiasis vaccine. Methods: recombinant proteins were expressed on a prokaryotic system, purified by different chromatographic methods and both immunochemically and spectroscopically characterized. Immunization experiments were made on females BALB/c mice and vaccines efficacy was assessed by analyzing the worm-burden after challenge infection with S. mansoni cercariae and by analyzing its effect on the hepatic granulomatous reactions around trapped eggs. Results: subcutaneous administration of Sm14 reduced in 27% the worm burden on animals. On the other hand, intranasally vaccination only displayed a statistically significant reduction when CTB was added to the formulation. Furthermore, coadministrating CTB and Sm14 reduces in 30% the area of hepatic granulomas. Conclusion: the use of CTB may be an important tool for mucosal adjuvanticity; however it did not provide, together with Sm14, satisfactory levels of protection on a murine model for Schistosomiasis infection.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-06-10T00:27:39Z No. of bitstreams: 1 JanainaSiqueiraBorda_TESE.pdf: 2734621 bytes, checksum: 45160291f3ca65a355a6a3fdda9a3569 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-06-13T19:59:16Z (GMT) No. of bitstreams: 1 JanainaSiqueiraBorda_TESE.pdf: 2734621 bytes, checksum: 45160291f3ca65a355a6a3fdda9a3569 (MD5) / Made available in DSpace on 2016-06-13T19:59:16Z (GMT). No. of bitstreams: 1 JanainaSiqueiraBorda_TESE.pdf: 2734621 bytes, checksum: 45160291f3ca65a355a6a3fdda9a3569 (MD5) Previous issue date: 2015-08-26 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O sistema ?ptico acess?rio, o Complexo pr?-tectal, e o col?culo superior s?o importantes centros de controle de uma variedade de movimentos oculares, sendo extremamente necess?rios para a forma??o de imagem, consequentemente para a percep??o visual. O sistema ?ptico acess?rio ? constitu?do pelos n?cleos: n?cleo terminal dorsal, n?cleo terminal lateral, n?cleo terminal medial e n?cleo intersticial do fasc?culo superior posterior. Do ponto de vista funcional eles contribuem para a estabiliza??o da imagem, participando da atividade visuomotora onde todas as c?lulas do sistema respondem a movimentos lentos dos olhos e a est?mulos visuais, o que ? importante para o pr?prio funcionamento dos outros sistemas visuais. O complexo pr?-tectal compreende um conjunto de n?cleos situados na transi??o mesodiencef?lica, s?o eles: n?cleo pr?-tectal anterior, n?cleo pr?-tectal posterior, n?cleo pr?-tectal medial, n?cleo pr?-tectal olivar e o n?cleo do trato ?ptico, sendo todos recipientes de proje??o retiniana e funcionalmente est?o relacionados com a via do reflexo pupilar a luz e o nistagmo optocin?tico. O col?culo superior ? uma importante esta??o visual subcortical formado por camadas e, apresenta um papel funcional importante no controle dos movimentos dos olhos e da cabe?a em resposta a est?mulos multissensoriais. Nosso objetivo foi fazer um mapeamento das proje??es retinianas que incidem sobre o sistema ?ptico acess?rio, os n?cleos do complexo pr?-tectal e os do col?culo superior, buscando principalmente, no caso do complexo pr?-tectal, uma melhor delimita??o dessas estruturas, por meio do rastreamento anter?grado com a subunidade B da toxina col?rica (CTb) seguido de t?cnica imunoistoqu?mica e, caracterizar (medir ?rea e di?metro) os bot?es sin?pticos presentes nas fibras/terminais dos n?cleos do complexo pr?-tectal. Em nossos resultados o sistema ?ptico acess?rio, incluindo uma regi?o que parece ser o n?cleo terminal medial, e o col?culo superior apresentaram-se fortemente marcados por fibras/terminais imunorreativos a CTb, bem como o complexo pr?-tectal nos n?cleos: n?cleo trato ?ptico, n?cleo pr?-tectal olivar, n?cleo pr?-tectal anterior e n?cleo pr?-tectal posterior. De acordo com a caracteriza??o dos bot?es foi poss?vel fazer uma melhor delimita??o desses n?cleos. / The accessory optical system, the pretectal complex, and superior colliculus are important control centers in a variety of eye movement, being extremely necessary for image formation, consequently to visual perception. The accessory optical system is constituted by the nuclei: dorsal terminal nucleus, lateral terminal nucleus, medial terminal nucleus and interstitial nucleus of the posterior superior fasciculus. From a functional point of view they contribute to the image stabilization, participating in the visuomotor activity where all system cells respond to slow eye movements and visual stimuli, which is important for the proper functioning of other visual systems. The pretectal complex comprises a group of nuclei situated in mesodiencephalic transition, they are: anterior pretectal nucleus, posterior pretectal nucleus, medial pretectal nucleus, olivary pretectal nucleus and the nucleus of the optic tract, all retinal projection recipients and functionally are related to the route of the pupillary light reflex and the optokinetic nystagmus. The superior colliculus is an important subcortical visual station formed by layers and has an important functional role in the control of eye movements and head in response to multisensory stimuli. Our aim was to make a mapping of retinal projections that focus on accessory optical system, the nuclei of pretectal complex and the superior colliculus, searching mainly for pretectal complex, better delineation of these structures through the anterograde tracing with the B subunit of cholera toxin (CTb) followed by immunohistochemistry and characterized (measured diameter) synaptic buttons present on the fibers / terminals of the nucleus complex pr?-tectal. In our results accessory optical system, including a region which appears to be medial terminal nucleus and superior colliculus, were strongly marked by fibers / terminals immunoreactive CTb as well as pretectal complex in the nucleus: optic tract, olivary pretectal nucleus, anterior pretectal nucleus and posterior pretectal nucleus. According to the characterization of the buttons it was possible to make a better definition of these nucleus.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-01-27T13:17:21Z No. of bitstreams: 1 MelquisedecAbiareDantasDeSantana_TESE.pdf: 3116458 bytes, checksum: e08973d68406997298f259956c431887 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-01-31T12:12:18Z (GMT) No. of bitstreams: 1 MelquisedecAbiareDantasDeSantana_TESE.pdf: 3116458 bytes, checksum: e08973d68406997298f259956c431887 (MD5) / Made available in DSpace on 2017-01-31T12:12:18Z (GMT). No. of bitstreams: 1 MelquisedecAbiareDantasDeSantana_TESE.pdf: 3116458 bytes, checksum: e08973d68406997298f259956c431887 (MD5) Previous issue date: 2016-09-09 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Em muitos vertebrados, a maior parte do c?rebro est? envolvidano processamento da vis?o, mais do que a qualquer outra modalidade sensorial. Isto se deve provavelmente ? extrema complexidade da tarefa que ? exigida da vis?o: classificar e interpretar a ampla gama de est?mulos visuais que os animais confrontam no ambiente f?sico. A retina modifica e processa sinais evocados pela luz nos fotorreceptores que depois s?o enviados a centros superiores pelas c?lulas ganglionares. Os ax?nios destas c?lulas formam os nervos ?pticos que distribuem a informa??o visual a estruturas encef?licas com diversas fun??es, como o n?cleo geniculado lateral dorsal (GLD), do qual a informa??o visual ascende ao c?rtex cerebral; o col?culo superior (CS), respons?vel por integrar sinais visuo-motores; e o complexo pr?-tectal (CPT), envolvido no controle do reflexo pupilar ? luz e no nistagmo optocin?tico. Como objetivo de descrever a citoarquitetura e o padr?o de proje??o retiniana nestas estruturas no morcego Artibeus planirostris, foram realizadas inje??es intra-oculares de CTb e analisadas sec??es coronais do enc?falo coradas pelo m?todo de Nissl e sec??es submetidas ? imunoistoqu?mica para CTb. Quanto ao padr?o citoarquitet?nico, o GLD apresentou-se como um n?cleo homog?neo e sem lamina??o aparente. Entretanto, quanto a proje??o retiniana o n?cleo apresentou duas camadas com intensidade de marca??o significativamente diferentes, sendo a proje??o predominantemente contralateral. O CS foi identificado como uma estrutura laminar composta por sete camadas, onde a marca??o de fibras e varicosidades imunorreativos a CTb foi observada exclusivamente no lado contralateral, tendo como alvo as camadas zonal e cinzenta superficial. Foram identificados compondo o CPT os n?cleos pr?-tectal medial, pr?-tectal olivar, pr?-tectal anterior, pr?-tectal posterior e o n?cleo do tracto ?ptico, onde apenas o n?cleo pr?-tectal anterior n?o apresentou inerva??o da retina, sendo esta predominantemente contralateral para todos os demais n?cleos que comp?em o CPT. Em conjunto, os dados apontam a presen?a de especializa??es morfol?gicas nos n?cleos estudados n?o observadas previamente em outras esp?cies de quir?pteros e, finalmente, o presente trabalho ? o primeiro a abordar estereologicamente e morfometricamente essas ?reas em Yangochiroptera.

nÃo hà / A regiÃo nordeste do Brasil tem grande potencial para a produÃÃo de leite de cabra, e a qualidade do leite produzido à importante para garantir a oferta de um alimento seguro do ponto de vista nutricional e higiÃnico sanitÃrio aos consumidores. O leite de cabra tem alto valor nutricional e possui grande aceitaÃÃo, especialmente em comunidades carentes, uma vez que constitui importante fonte proteica de alta qualidade na dieta dessas pessoas. A distribuiÃÃo gratuita e diÃria do leite de cabra, por meio de programas governamentais, tem o objetivo de reduzir deficiÃncias nutricionais com prioridade para as crianÃas, as gestantes e as nutrizes. O Kit Embrapa de Ordenha Manual foi desenvolvido com o propÃsito de contribuir para a produÃÃo segura do leite, atravÃs de uma tecnologia de baixo custo, ao alcance dos produtores familiares, os quais sÃo responsÃveis por grande parte da produÃÃo de leite de cabra no Brasil. O objetivo deste trabalho foi avaliar o efeito do Kit Embrapa de Ordenha Manual para caprinos leiteiros em propriedades de agricultura familiar, localizadas em trÃs regiÃes do nordeste Brasileiro. Durante o perÃodo de maio de 2010 a fevereiro de 2011, foram colhidas amostras de leite de cabra provenientes de rebanhos dos Estados do CearÃ, ParaÃba e Rio Grande do Norte para determinaÃÃo da composiÃÃo, contagem de cÃlulas somÃticas (CCS) e contagem bacteriana total (CTB). Avaliou-se tambÃm os impactos ambientais e sociais do Kit atravÃs do Sistema Ambitec-Agro. ApÃs a implantaÃÃo do Kit nas propriedades estudadas, observou-se uma diminuiÃÃo mÃdia de 72,1% da CTB e preservaÃÃo das caracterÃsticas de composiÃÃo do leite. A avaliaÃÃo do efeito da CCS sobre os componentes mostrou que houve um decrÃscimo da porcentagem de lactose do leite conforme aumentou a CCS. Dentre as amostras analisadas, 64% apresentavam contagens superiores a 1.000.000 CCS/mL, antes da adoÃÃo do Kit, o que evidenciou a necessidade da implantaÃÃo das Boas PrÃticas de ordenha nas propriedades avaliadas. A avaliaÃÃo de impacto social e ambiental foi positiva, apresentando valores mÃdios de 1,07 e 0,9 na avaliaÃÃo ex-post para os Ãndices de impacto Ambiental e Social, respectivamente, mostrando o potencial desta tecnologia como parte de um conjunto de atitudes capazes de melhorar a qualidade do leite de cabra produzido no Brasil, assim como proporcionar ganhos aos produtores. / The northeastern region of Brazil has great potential for the production of goat milk, and the quality of the milk produced is important to ensure consumers a safe food supply from the nutritional and hygienic-sanitary standpoint. Goat milk has high nutritional value and has a wide acceptance, especially in poor communities, since it is an important protein source in the diet of these people. The free and daily distribution of the goat milk, through government programs, aims to reduce nutritional deficiencies with priority given to children, pregnant women and nursing mothers. The goal of this study was to evaluate the effect of the Kit Embrapa de Ordenha Manual for dairy goats in family farming, located in three regions of northeastern Brazil. This effect was evaluated in samples of goat milk on the composition, somatic cell count (SCC) and total bacterial count (TBC), and also the effect of SCC on the components, by correlation of the data. In parallel, we assessed the environmental and social impacts of the Kit through Sistema Ambitec-Agro. The Kit Embrapa de Ordenha Manual was developed with the purpose of safe milk production through a low-cost technology that is available to family farmers, who are responsible for much of the production of goat milk in Brazil. Its validation in properties of Paraiba, Rio Grande do Norte and Cearà brought positive results, as the average of TBC decreased 72% and the characteristics of milk composition were preserved. The evaluation of SCC effect on the milk components showed that there was a decrease in the percentage of lactose in milk as SCC increased. Among the samples analyzed, 64% had counts exceeding 1.000.000 CCS/mL. This highlights the need for the implementation of hygiene practices on the milking properties evaluated. The social and environmental impact was also positive, with average values of 1.07 and 0.9 in the ex post evaluation indexes for Environmental and Social Impact, respectively, showing the potential of this technology as part of a set of attitudes capable of improving the quality of goat milk produced in Brazil, as well as of providing gains to producers.

The primary purposes of this research were to identify construction factors most correlated to specific mechanical properties of cement-treated base (CTB) layers and to determine which construction factors exhibit comparatively high variability within individual construction sections of the two pavement reconstruction projects included in this study. In addition, differences between construction sections tested in this research were evaluated. The research focused on the construction of CTB layers in two pavement reconstruction projects in northern Utah, one along Interstate 84 (I-84) near Morgan and one along U.S. Highway 91 (US-91) near Richmond. The significant predictor variables associated with California bearing ratio (CBR), Clegg impact value (CIV), 7-day unconfined compressive strength (UCS), and 28-day UCS at the I-84 sites include reclaimed asphalt pavement (RAP) content; cement content; amounts of aggregate particles finer than the No. 8, No. 50, and No. 200 sieves; 7-day moisture content, and 28-day moisture content. The significant predictors of the same response variables on US-91 were in-situ moisture content, cement content, amount of aggregate particles finer than the No. 50 sieve, time between mixing and compaction in the field, dry density in the field, 7-day dry density, 7-day moisture content, 28-day dry density, and 28-day moisture content. The factors that were found to be the most variable on both I-84 and US-91 were CBR, cement content, time between mixing and compaction in the field, and time between mixing and compaction for each of the manually compacted specimens. On I-84, 16 of 27 factors were found to be significantly different between the sites, while 17 of 26 factors were found to be significantly different between the sites on US-91. The results of this research suggest that tighter specifications are warranted with respect to RAP content, cement content, and time between mixing and compaction. Concerning full depth recycling (FDR) projects, milling plans should be utilized to achieve improved uniformity in RAP content, and inspection protocols for encouraging improved control of cement content should be implemented during construction to ensure high-quality work. Compaction should be performed as soon as possible after mixing to minimize the adverse effects of cement hydration on the ability to achieve maximum dry density in the field.

Rotavirus, the major cause of life-threatening infantile gastroenteritis, is a member of the Reoviridae family and is considered to be the single most important cause of virus-based severe diarrheal illness in infants and young children particularly 6 months to 2 years of age in industrialized and developing countries. Infection in infants and young children is often accompanied by severe life threatening diarrhea, most commonly following primary infection. Diarrhea is the major cause of death among children around the world. Responsible for 4 to 6 million deaths per year according to the World Health Organization (WHO), diarrhea is especially dangerous for infants and young children. Globally, it is estimated that 1.4 billion episodes of diarrhea occur in children less than five years of age annually. In the United States alone, rotavirus causes more than 3 million cases of childhood diarrhea each year, leading to an estimated 55,000 to 100,000 hospitalizations and 20 to 100 deaths. And is a major cause of mortality for children in developing countries with approximately one million deaths annually. Rotaviruses belong to the family Reoviridae and are spherical 70-nm particles. The virus genome contains 11 segments of double-stranded RNA, each encoding a viral capsid or nonstructural protein. The identification of a rotavirus nonstructural protein gene (NSP4) encoding a peptide, which functions both as a viral enterotoxin and as a factor involved in the acquisition of host cell membrane during virus budding from cells, provides a new approach for mucosal immunization. Protein expression through chloroplast transformation system offers a number of advantages like high level of transgene expression, transgene containment via maternal inheritance, lack of gene silencing and position effect due to site specific gene integration and also the possibility of multi gene engineering in single transformation event. It is also an environmentally friendly approach due to effective gene containment and lack of transgene expression in pollen. To achieve an enhanced immune response to rotavirus infection, a fusion gene encoding the cholera toxin B subunit linked to rotavirus enterotoxin 90 aa protein (CTB-NSP490) was introduced into transgenic chloroplast and was transformed into chloroplast genome of Nicotiana tabacum by homologous recombination. The chloroplast integration of CTB-NSP4(90) fusion gene was confirmed in transgenic tobacco plants by PCR analysis. Southern blot analysis further confirmed site specific gene integration and homoplasmy. Immunoblot analysis of transformed chloroplast confirmed the expression of CTBNSP490 fusion protein both in monomeric and pentameric forms that retained the binding affinity to the enterocytes GM1 ganglioside receptor. Expression levels of CTB-NSP4 protein was quantified by GM1 ganglioside binding ELISA assay; mature leaves expressed CTB-NSP4 fusion protein to upto 2.45 % in total soluble protein, 100-400 fold higher than nuclear expression which was only 0.006%-0.026%. Antibody titration and virus challenge experiments will be performed in mice at Loma Linda University to evaluate the antigenic and protective properties of the chloroplast derived CTB-NSP4 fusion protein.

La tos convulsa es una enfermedad aguda, respiratoria y altamente contagiosa que a pesar de ser inmunoprevenible, hoy en día es considerada una enfermedad resurgente. Surge entonces la necesidad de aplicar refuerzos de inmunización de forma de prolongar la duración de la inmunidad contra la enfermedad, así como también de mejorar las vacunas actuales de manera tal que no solo ofrezcan una protección duradera en el tiempo sino que también protejan contra cepas circulantes antigénicamente distintas. Es por esto que la inclusión de antígenos expresados por cepas circulantes en las formulaciones vacunales podría ofrecer una mejora en el control de esta enfermedad Por otra parte, ante las vacunas parenterales convencionales, una vacuna mucosal podría ser una alternativa válida para mejorar las vacunas existentes, ya que imita a la infección natural y puede prevenir la colonización de B. pertussis mediante la generación de anticuerpos en la mucosa. Sin embargo, la inducción de una respuesta inmune protectora es difícil de lograr mediante inmunización por vía mucosal con antígenos recombinantes solubles. Es por ésto que el uso correcto de adyuvantes es fundamental a la hora de diseñar vacunas recombinantes administradas por vía de mucosas. En este sentido, se ha demostrado que la subunidad B de la toxina colérica es un potente inmunoestimulador que puede actuar como adyuvante estimulando la respuesta inmune sistémica y de mucosas contra antígenos administrados por vía mucosal, además de ser seguro para su uso en humanos. Con el objetivo de contribuir al desarrollo de una vacuna recombinante acelular para la mejora de la prevención de la infección por B. pertussis, el objetivo general de este trabajo fue generar herramientas moleculares que resulten útiles en el control de la infección causada por B. pertussis. Nuestro trabajo contempló la identificación, caracterización, y la validación de proteínas de B. pertussis como candidatos vacunales así como el estudio de la respuesta del huésped a dichas proteínas. Nuestra hipótesis es que proteínas recombinantes de B. pertussis fusionadas con CTB son buenos candidatos vacunales para ser utilizados por vía mucosal.

In order to avoid the occurrence of early-age damage, cement-treated base (CTB) materials must be allowed to cure for a period of time before the pavement can be opened to traffic. Trafficking of a CTB before sufficient strength gain has occurred can lead to marring or rutting of the treated layer. The specific objectives of this research were to examine the correlation between Clegg impact values (CIVs) determined using a heavy Clegg impact soil tester and rut depths measured in newly constructed CTB and subsequently establish a threshold CIV at which rutting should not occur.The experimental work included field testing at several locations along United States Highway 91 near Smithfield, Utah, and laboratory testing at the Brigham Young University (BYU) Highway Materials Laboratory. In both the field and laboratory test programs, ruts were created in CTB layers using a specially manufactured heavy wheeled rutting device (HWRD). In the field, ruts caused by repeated passes of a standard pickup and a water truck were also evaluated. The collected data were analyzed using regression to identify a threshold CIV above which the CTB should not be susceptible to unacceptable rutting. From the collected data, one may conclude that successive wheel passes each cause less incremental rutting than previous passes and that CTB similar to the material tested in this research should experience only negligible rutting at CIVs greater than about 35. The maximum rut depth measured in either field or laboratory rutting tests was less than 0.35 in. in this research, probably due to the high quality limestone base material utilized to construct the CTB. In identifying a recommended threshold CIV at which CTB layers may be opened to early trafficking, researchers proposed a maximum tolerable rut depth of 0.10 in. for this project, which corresponds to a CIV of approximately 25. Because a CIV of 25 is associated with an acceptably minimal rut depth even after 100 passes of the HWRD, is achievable within a reasonable amount of time under normal curing conditions, and is consistent with earlier research, this threshold is recommended as the minimum average value that must be attained by a given CTB construction section before it can be opened to early trafficking. Use of the proposed threshold CIV should then ensure satisfactory performance of the CTB under even heavy construction traffic to the extent that the material properties do not differ greatly from those of the CTB evaluated in this research.

L’acétylcholine (ACh) endogène de la corne dorsale de la moelle épinière (CDME) exerce une analgésie puissante utilisée en clinique, dont la source et les mécanismes demeurent inconnus. Elle siège probablement au niveau d’un plexus de fibres cholinergiques de la CDME d’origine non-élucidée. Dans ce contexte, nous avons pu établir que ce plexus est principalement issu d’interneurones cholinergiques spinaux caractérisés dans ces travaux, qui seraient donc le substrat probable de l’analgésie décrite. Décrits comme concourant aux effets aigus et analgésiques de la morphine, nous avons, par ailleurs, pu observer que les récepteurs de l’ACh participaient également aux effets chroniques et pro-algésique de la morphine, notamment au niveau de la CDME. Ceci place donc l’ACh comme un effecteur ou intermédiaire de la morphine.Nos travaux suggèrent ainsi que le système cholinergique spinal pourrait constituer une cible thérapeutique alternative pour de nouveaux traitements de la douleur / In the spinal cord dorsal horn (SCDH), endogenous acetylcholine (ACh) acts as a powerful analgesia, of clinical use. Though its source and mechanisms remain unravelled, this analgesia probably lies in a plexus of cholinergic fibers (PCF) located in the SCDH and of undetermined origin. In this context, we established that the PCF mainly originates from a spinal population of cholinergic interneurons, fully characterized in this work. These are, thus, the likely substrate of the spinal cholinergic analgesia.Besides, ACh receptors (AChR) partly mediate the analgesic acute effects of morphine. In this work, we also observed that a chronically-administered AChR agonist reproduces as well the pro-algesic effects of morphine in the same conditions. Thus, ACh appears as a possible intermediary or a final effecter of the morphine pain pathways.Our data suggest that the cholinergic system could become a new putative therapeutic target in pain management and treatment.

No description available.