Thesis (M.S.)--Indiana University, 2006. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--Indiana University, 2006. / Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 4 uppsatser.

Thesis (doctoral)--Katholieke Universiteit te Nijmegen.

Includes bibliographical references and index.

Orientador: Cristina Elena Prado Teles Fregonesi / Banca: Dalva Minonroze Albuquerque Ferreira / Banca: Marli Aparecida Defani / Resumo: O objetivo do estudo foi verificar a estabilidade do ato de locomoção em diabéticos com neuropatia periférica, em três situações: marcha habitual com os olhos abertos; marcha com os olhos fechados e marcha com olhos abertos e diminuição da base de sustentação. Participaram do estudo 41 indivíduos, sendo 18 do grupo neuropata e 23 do grupo controle (GC). A avaliação da estabilidade foi realizada por meio de um baropodômetro associado ao software Footwalk Pro. Os dados obtidos foram: velocidade da marcha e porcentagens de tempo de duplo apoio e de apoio simples. Foram encontradas diferenças significantes nas três situações entre os grupos para a velocidade e tempo de apoio simples, com diminuição para o grupo neuropata (p<0,05), e tempo de duplo apoio, com aumento para esse grupo (p<0,05) em todas as condições. Para os dados de velocidade, tempo de duplo apoio e tempo de apoio simples, a condição de olho aberto foi diferente da condição de olho fechado (p=0,001) e da condição com diminuição da base de sustentação (p=0,001). Foi possível observar que nas três situações avaliadas, o grupo neuropata apresentou déficit na estabilidade do ato de locomoção e tal desempenho foi ainda mais comprometido nas duas situações que exigiam mais do controle postural. Tais modificações da marcha, decorrentes da complexidade imposta pelas diferentes condições, sugerem a inserção destas na avaliação e no tratamento dessa população / Abstract: The aim of this study was to verify the stability of the act of locomotion in diabetics with peripheral neuropathy in three situations: habitual gait with eyes opened, gait with eyes closed, and gait with eyes opened and reduced base of support. The study included 41 subjects: 18 of the neuropathic group and 23 in the control group. The stability was evaluated by baropodometry platform associated with the software Footwalk Pro. Data were obtained: gait speed and percentual of double stance time and single stance time. Significant differences were found in the three cases between the groups in the data of gait speed and single stance time, with a larger reduction for neuropathic group (p<0,05) and increased in double stance time in the neuropathic group (p<0,05) in all conditions. For data of gait speed measure, double stance time and single stance time, the condition eyes opened was different from eyes closed (p=0,001) and from the condition with reduced base of support (p=0,001). It was observed that in the three situations evaluated, the neuropathic group showed stability locomotion deficit and the performance was more injured in both situations that required more postural control. Such gait modifications, due to the complexity imposed by different conditions, suggest the inclusion of these in the evaluation and treatment of this population / Mestre

No description available.

L'objectif de notre travail était dans un premier temps d'étudier les liens entre l'altération des fibres nerveuses de petit diamètre et la présence de douleurs chez des patients ayant une neuropathie périphérique. Notre deuxième objectif était d'évaluer la pertinence de certaines techniques neurophysiologiques pour mettre en évidence l'atteinte de ces petites fibres nerveuses. Notre première étude réalisée sur une large cohorte de patients présentant divers types de neuropathie a montré, grâce à une étude quantifiée de la sensibilité, qu'il n'y avait pas de corrélation entre la perte ou perte de fonction des fibres nerveuses de petit diamètre et la présence de douleurs. Ceci a été confirmé par notre deuxième étude portant sur une population plus homogène de patients ayant une neuropathie amyloïde familiale et étudiés avec une batterie neurophysiologique plus large. Ainsi, les douleurs neuropathiques des patients présentant une neuropathie périphérique sont probablement dues à la combinaison de facteurs d'hyperexcitabilité périphérique et de sensibilisation centrale et non directement liée à la perte en petites fibres. Il reste cependant pertinent de développer des techniques objectives d'exploration de ces petites fibres notamment dans un but de diagnostic clinique. Notre troisième étude a montré que certaines méthodes neurophysiologiques étaient particulièrement sensibles dans ce cadre en prenant pour exemple la détection d'anomalies précoces d'atteinte des petites fibres au cours de la neuropathie amyloïde familiale. Une batterie de tests comprenant l'enregistrement des potentiels évoqués laser, la mesure du seuil de détection du chaud et de la conductance cutanée, s'est avérée être la combinaison la plus pertinente, comme l'a montré notre quatrième étude sur une grande cohorte de patients susceptibles de présenter une neuropathie des petites fibres. / The aim of our work was initially to study the relationship between alterations in small diameter nerve fibers and the presence of pain in patients with peripheral neuropathy. Our second objective was to assess the relevance of some neurophysiological tests to characterize these alterations in small nerve fibers. Our first study of a large cohort of patients with various types of neuropathy showed, using quantitative sensory testing, that there was no correlation between the loss or loss of function of small nerve fibers and the presence of pain. This was confirmed by our second study focused on a more homogeneous population of patients with familial amyloid neuropathy and studied with a larger neurophysiological battery. Thus, neuropathic pain in patients with peripheral neuropathy is probably due to a combination of factors of peripheral hyperexcitability and central sensitization and not directly related to the loss of small nerve fibers. However, it remains relevant to develop techniques of objective investigation of these small nerve fibers for a purpose of clinical diagnosis. Our third study showed that some neurophysiological methods were particularly sensitive in this context, taking the example of the detection of early alteration of small nerve fibers in familial amyloid neuropathy. A battery of tests, including laser evoked potential recording, warm detection threshold and electrochemical skin conductance measurement, proved to be the most appropriate combination for this diagnostic purpose, as shown by our fourth study on a large cohort of patients likely to have a small fiber neuropathy.

Les douleurs neuropathiques se caractérisent par l’apparition de symptômes positifs tels qu’une allodynie et de symptômes négatifs tel qu’une hypoalgésie. Les douleurs neuropathiques ont un retentissement important sur la qualité de vie et il n’existe à ce jour aucune thérapie efficace pour leur prise en charge préventive. Récemment, un système rénine-angiotensine tissulaire a été mis en évidence au sein du système nerveux périphérique sensitif et il a été démontré que sa modulation pharmacologique modifie la perception douloureuse chez l’animal. Dans ce travail, nous nous sommes intéressés à la physiopathologie et à la prévention thérapeutique des neuropathies sensitives par des modulateurs du SRA. Pour cela, deux modèles murins de neuropathie sensitive à l’origine de douleurs neuropathiques ont été utilisés ; un modèle de neuropathie induite par la résinifératoxine (RTX), toxine naturelle spécifique des petites fibres nociceptives et un modèle de neuropathie induite par la vincristine (VCR), un agent anticancéreux particulièrement neurotoxique. Une étude pharmacologique menée sur la neuropathie induite par la RTX nous a permis de mettre en évidence que seul le candésartan prévenait le développement de la neuropathie et que son effet était AT2R-dépendant. L’efficacité du candésartan a été confirmée dans le modèle de neuropathie chimio-induite, développé et caractérisé au cours de ce travail. Ce modèle de neuropathie induite par la VCR a permis de révéler, pour la première fois, le potentiel neuroprotecteur du C21 (agoniste direct du récepteur AT2R, Vicore Pharma) dans un contexte de neuropathie périphérique. L’ensemble de ces résultats confirme l’intérêt de la stimulation du récepteur AT2R dans le traitement des douleurs neuropathiques associées à une chimiothérapie, et plus largement d’origine toxique. / Neuropathic pain was characterized by positive symptoms as allodynia and negative symptoms as hypoalgesia. Neuropathic pain has a major impact on patient’s quality of life and there is, currently, no specific treatment for its preventive management. Recently, a specific renin angiotensin system in sensory peripheral nervous system has been showed and it has been demonstrated that its pharmacological modulation could modify pain perception in animals. In this work, we studied the neuroprotective potential of RAS modulators in two animal models of sensory neuropathy leading to neuropathic pain; a model of neuropathy induced by resiniferatoxin (RTX), a specific natural toxin of nociceptive nerve fibers, and a model of neuropathy induced by vincristine (VCR), a neurotoxic anticancer agent. Pharmacological study on mice with RTX-induced neuropathy allowed to conclude that only candesartan was neuroprotective and that its effect was AT2R-dependent.The effective neuroprotective effect of candesartan was confirmed on the model of VCR-induced neuropathy which was previously developed and characterized. This VCR-induced neuropathy mouse model allowed to demonstrate, for the first time, that C21 (a direct AT2R receptor agonist, Vicore Pharma) was neuroprotective against a peripheral neuropathy. All these results confirm the interest of stimulation of the AT2R receptor in the treatment of neuropathic pain associated with chemotherapy and more generally of toxic origin.