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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
221

Die Beiträge von Paul Julius Möbius (1853-1907) zu den Konzeptgeschichten der Migräne, Neuroophthalmologie und des Morbus Basedow

Engelmann, Constanze 16 June 2016 (has links)
Der erste Schwerpunkt der vorliegenden Arbeit resümiert den neurologischen Forschungsstand Ende des 19. Jahrhunderts zum Thema Migräne. Vergleichend dazu wird das Wirken des Leipziger Neurologen, Psychiaters und Wissenschaftspublizisten Paul Julius Möbius (1853-1907) zu diesem Krankheitsbild betrachtet. Folglich wird in der ersten Publikation seine 1894 erschienene Monographie „Die Migräne“ mit zeitgenössischen, heute teils als medizinhistorische Standardwerke geltenden, Werken europäischer Kollegen korreliert. Als Ergebnis wird formuliert, dass sich die Ansichten von Möbius und seiner Kollegen in vielen Aspekten gleichen. Möbius‘ Migräne-Konzept zeichnet sich demnach weniger durch Originäres aus, aber mit seiner, das Wissen der Zeit sammelnden Monografie legte er eines der Standardwerke der deutschsprachigen Neurologie um 1890 zur Migräne vor. Der zweite Schwerpunkt trägt Arbeiten Möbius\'' zum heutigen Gebiet der Neuroophthalmologie zusammen. Die Arbeit kommt angesichts des Forschungsstandes seiner Zeit zu der Schlussfolgerung, dass Möbius zu den Entitäten Periodischer Okulomotoriuslähmung, infantilem Kernschwund und Morbus Basedow Pionierarbeiten geleistet hat. Dies war bisher unbekannt. Ein Ziel dieser Arbeit ist es, laufende evaluierende Forschungen über die in verschiedene Gebiete einzuordnenden Leistungen des Arztes und Wissenschaftlers Paul Julius Möbius zu fundieren, dessen Leumund durch seine Schrift „Über den pathologischen Schwachsinn des Weibes“ als beschädigt gelten muss. Für die Gebiete der Neurologie und Neuroophthalmologie gilt es festzuhalten, dass er wesentliche fachwissenschaftliche Beiträge geleistet hat.
222

Kathodale transkranielle Stromstimulation des visuellen Kortex als Verfahren zur prophylaktischen Behandlung der Migräne / Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine

Kriener, Naomi 31 March 2021 (has links)
No description available.
223

How the use of gamification in migraine tracking effects the perceived feeling of motivation

Ljungholm, Alice January 2022 (has links)
The problem with logging migraines is that patients often forget, or simply choose not to log their migraines. To solve this problem, we investigate in this thesis whether gamification can make a difference in their motivation. To investigate whether gamification makes a difference, an AB test was performed. An A prototype, without gamification, and a B prototype, without gamification, were developed in the initial phases of this thesis, these were tested on people outside of the target group. Motivation was measured using Self Determination Theory and its sub-theory Organic integration. Gamification elements chosen to use in the B-prototype is based on the desired feel of the prototype, the elements included an avatar, badges, and progress bars. The A/B-test was performed on 10 people, 5 for each prototype, and all the participants were diagnosed with migraine and had some previous experience of logging their migraines and symptoms. The result includes interview questions about their experience, observations of user tests and answers from a questionnaire. The results showed no significant overall difference between the two prototypes; however, discussion and some hypotheses can be created by the results. Most difference between the results can be seen in integration regulation, a subcategory of motivation, where the prototype without gamification got a higher result. / Detta examensarbete kommer att undersöka möjligheten att använda gamification i mobila applikationer för migränpatienter, för att se om det kommer att hjälpa migränpatienter med deras loggning. Problemet med att logga migrän är att patienter ofta glömmer, eller helt enkelt väljer att inte logga sin migrän. För att lösa detta problem undersöker vi i detta examensarbete om gamification kan göra skillnad i deras motivation. För att undersöka om gamification gör skillnad gjordes ett AB-test. En A-prototyp, utan gamification, och en B-prototyp, utan gamification, utvecklades i de inledande faserna av detta examensarbete, dessa testades på personer utanför målgruppen. Motivation mättes med hjälp av Self Determination Theory och dess underteori Organic integration. Gamification-element som valts att använda i B-prototypen är baserade på den önskade känslan av prototypen, elementen inkluderade en avatar, badges och progressbar. A/B-testet utfördes på 10 personer, 5 för varje prototyp, alla deltagare var diagnostiserade med migrän sedan innan och hade tidigare erfarenhet av att logga sin migrän och symptom. Resultatet inkluderar intervjufrågor om deras upplevelse, observationer av användartester och svar från en frågeenkät. Resultaten visade ingen signifikant skillnad mellan de två prototyperna, men diskussion och vissa hypoteser kan skapas av resultaten. Mest skillnad mellan resultaten kan ses i integration regulation, en underkategori av motivation, där prototypen utan gamification resultat visa högre nummer på likert-skalan.
224

Analysis of the Pathomechanism of Migraines with a Focus on Current Treatment Plans and the Role of the Neuropeptide CGRP

Qureshi, Marvi 01 May 2015 (has links)
Migraines are a type of headache that specifically act on only one side of the head, although about 30% of patients with migraine may experience a bilateral headache. Migraine is a brain disorders that typically involve issues of the typical sensory processing that takes place in the brainstem. Possible causation has been linked to issues in blood vessels, blood flow, and oxygen levels in the brain. Migraine can be described in three phases, and common throughout the three phases is the importance of the neuropeptide CGRP and its role in migraine pathogenesis. CGRP increases in plasma have been linked to migraine headaches, and specific treatment plans have been tailored to account for this. CGRP is a vasodilator that causes dilation of cranial blood vessels and can lead to possible neurogenic inflammation in the periphery of its release while activating the pain pathway in the brainstem. The primary treatment for migraines is currently drugs from the triptan family and NSAIDs, as well as prophylactic drugs including antiepileptic drugs, beta-blockers, and Ca2+ channel blockers. The experiment conducted for this project aimed to determine the effects of a specific CGRP polyclonal antibody and CGRP receptor antagonist when it is with capsaicin, which stimulates sensory nerves. In an ex-vivo experiment using cell culture medium, the dura mater of mice is given either rabbit polyclonal antibody or a CGRP receptor antagonist or both, and then is challenged with capsaicin. CGRP positive (expressing) fibers and nerve terminals are examined under a fluorescent microscope in the dura mater of the mice.
225

Menstrually Related and Nonmenstrual Migraines in a Frequent Migraine Population: Features, Correlates, and Acute Treatment Differences

Pinkerman, Brenda F. 16 May 2006 (has links)
No description available.
226

The relationship between temperament and serum serotonin concentration in migraine without aura

Harvey, Jaqueline Ceridwyn 05 1900 (has links)
Cloninger’s Psychobiological Theory of Personality proposes four temperament dimensions, each underpinned by a different neurotransmitter system. The serotonergic system is purportedly linked to Harm Avoidance (HA). The aim of this study was to explore the relationship between HA and serotonin in migraine without aura (MO). A second aim was to explore the personality profile of MO patients. Sixty-six participants completed an online questionnaire and donated blood samples. Results indicated no significant association between HA and serotonin and a significant relationship between MO and HA. This study indicates that both Cloninger’s Psychobiological Theory of Personality and the Tridimensional Personality Questionnaire used for its assessment have value in South African personality research. In addition, the findings of the study reveal support for personality influences on the processes involved in migraine. This not only produces worthwhile avenues of research but also an alternative perspective for clinical practice. / Psychology / M.A. (Psychology (Research Consultation))
227

Estudo sobre a efetividade da técnica de biofeedback em grupo de doentes com migrânea crônica / Study about the biofeedback technique effectiveness in group with chronic migrainers

Perissinotti, Dirce Maria Navas 30 March 2007 (has links)
O biofeedback (BFD) é uma estratégia terapêutica em que ocorre aprendizagem por associação de sensações com o propósito de controlá-las levando a melhor enfrentamento fornecendo novas respostas e permitindo novos padrões, mesmo que se mantenha a ativação dos estímulos originais disfuncionais. Em migranosos ocorreria inibição da expressão da angústia relacionada ao nível fisiológico, devido a persistência de estados induzidos de estresse. Pesquisas de enfrentamento da migrânea incluem tratamento por condicionamento operante, biofeeback e outras técnicas como tratamento psicodinâmico. Tais tratamentos apontam para a redução do reforçamento do comportamento doloroso e melhora de comportamentos adaptativos para o enfrentamento das dificuldades. Objetivo geral: verificar a efetividade da técnica do biofeeback térmico como tratamento auxiliar em migranosos, através do Multidimensional Pain Inventory (MPI), antes e depois da intervenção. População: 60 doentes (masculino e feminino); idade variando entre 20 e 60 anos, com duração dos sintomas superior à 6 meses; em condições de locomoção e retorno às consultas e aceite do termo de Consentimento Pós-Informado CAPPesq. Instrumentos e Procedimento: Entrevista psicológica semi-dirigida para doentes com dor, através de protocolo próprio (Perissinotti, 2001); PRIME-MD + Qp; ABIPEME; Multidimensional Pain Inventory - MPI; ProComp + BioGraph 2.1. Duas amostras randomizadas foram separadas: grupo experimental (30 doentes) e grupo comparativo (30 doentes). O procedimento foi composto por triagem e direcionamento para grupo experimental, treinamento por BFD, 10 sessões que objetivaram o treino de dimensão de sensibilização discriminativa; e para o grupo comparativo adotado tratamento médico preventivo com medicação profilática padrão, para crise de migrânea. Resultados: O BFD alterou o comportamento da amostra experimental estudada, ocorrendo melhora geral da adaptabilidade, quando dos cálculos pela análise paramétrica. Quando da análise pelo teste qui-quadrado para variáveis qualitativas, houve resultados significantes para a amostra experimental, quanto aos sinais e sintomas psicopatológicos, qualidade das queixas e qualidade da saúde auto-referida. Houve diminuição da escala de intensidade de dor com BFD de 5,0 (83,3%) no pré-tratamento, e para 3,15 (52,5%) no pós-tratamento. Mostraram-se sem anormalidades mentais 20 doentes (60%) da amostra experimental. Transtornos de ansiedade foram encontrados em 11 doentes (36,6%) e transtorno depressivo em 9 doentes (33,3%). Para 18 (60%) doentes da amostra experimental o BFD melhorou as condições psicológicas, e para 14 (46,6%) doentes a melhora estaria relacionada exclusivamente ao relacionamento interpessoal, conjugal, afetivo e psicocomportamental. Para 4 (13,3%) deles primariamente reconheceram melhora no enfrentamento das condições psicofisiológicas, além dos aspectos psicológicos associados. Conclusões: O BFD alterou o comportamento da amostra experimental, fornecendo maior adaptabilidade geral, quando da análise paramétrica. Foi possível a ruptura do círculo vicioso entre percepção, tensão, estresse e dor, também pelo relacionamento estabelecido entre psicólogo e paciente. O psicólogo, portanto operador do método que calculou aspectos psicopatógicos, psicodinâmicos, além de servir como aquele que certifica as percepções do paciente consigo mesmo e suas expressões psicofisiológicas, é o operador funcional como um todo. Futuras pesquisas devem se desenvolver para esclarecer a compreensão entre os mecanismos psicofisiológicos que induzem a diferentes interpretações em distintos sintomas e as subseqüentes respostas psicofisiológicas quanto aos aspectos psicológicos dos migranosos. / Biofeedback (BFD) is a therapeutic strategy in which occurs the learning by the sensations association, with the purpose of controlling them leading to a behavior of better copping because provides new responses permitting new patterns, even with a new activation of dysfunctional original stimuli. In migrainers there would be the inhibition of anger expression related to the physiological level due to persistence of stressor-induced activation states. The migraine management research includes operant behavior treatment, biofeeback and other techniques as psychodynamic treatments. These treatments point out to reduce the reinforcement for pain behaviors and to improve adaptative behaviors to copping difficulties. General Objective: Verify the thermal biofeeback technique effectiveness as an auxiliary treatment in migraine patients by Multidimensional Pain Inventory (MPI), before and after intervention. Population: 60 patients (female and male): variance age between 20 and 60 years old, symptoms duration superior to 6 months, in condition to locomotion, to return to consultation and acceptance of the Post-Informed Consenting Term CAPPesq. Instruments and Procedure: Semi-directed structured psychological interviews for pain patients by Owner Protocol (Perissinotti, 2001); PRIME MD + PQ; ABIPEME; Multidimensional Pain Inventory - MPI; ProComp + BioGraph 2.1. Two random samples were separated: experimental group (30 patients) and comparative group (30 patients). The procedure was composed by triage and directionless: for experimental group, the BFD training, 10 sessions for sensitive-discriminative dimension training; for comparative group, the preventive medical treatment with standard prophylactic medication for migraine crisis. Results: The BFD has interfered in the behavior of the experimental sample studied, occurring a general better in adaptability, when calculated the parametric analysis. When the analysis by qui-square test for qualitative variables, there were significant results to the experimental sample, as to psychopathological signs and symptoms, quality of complains and quality of auto-referred health. The pain severity scale has decreased with BFD into 5.0 (83.3%) in the pre-treatment and into 3.15 (52.5%) in the post-treatment. No mental abnormalities were seen in 20 patients (60%) of the experimental sample. Anxiety disorders were found in 11 patients (36.6%) and depressions disorders in 9 patients (33.3%). For 18 (60%) patients of the experimental sample, the BFD improved the psychological conditions, and for 14 (46.6%) patients we could relate improving exclusively in interpersonal, conjugal, affective and behavior relationship. For 4 (13.3%) of them, primarily was recognized improvement in the psychophysiological conditions, further to the psychological aspects associated. Conclusions: The BFD has interfered in the behavior of the experimental sample, providing bigger general adaptability on the occasion of the parametric analysis. It was possible the break of the vicious circle among perception, tension, stress and pain, also by the relationship established between psychologist and patient. The psychologist, the method operator which has calculated the psychopathologic, psychodynamic aspects, besides of being the one who certifies the patient perceptions with himself and his psychophysiological expressions, is the functional operator of the whole. Future researches must be developed to clarify the comprehension between the psychophysiological mechanisms inducing different kinds of interpretation in distinct symptoms, and the subsequent psychophysiological responses as to psychological aspects in migrainers.
228

Frequência e severidade da disfunção temporomandibular em mulheres com migrânea e migrânea crônica / Frequency and severity of temporomandibular disorders (TMD) in women with migraine and chronic migraine

Gonçalves, Maria Claudia 26 February 2010 (has links)
A Migrânea e a Disfunção Temporomandibular (DTM) são doenças crônicas e tem como aspecto mais importante a dor crônica. Muitos trabalhos descrevem sinais e sintomas de DTM em pacientes com cefaleia sugerindo uma associação entre essas duas condições. Porém, ainda são poucos os trabalhos que utilizaram um critério que fornecesse não apenas sinais e sintomas, mas também a classificação diagnóstica. Assim, o objetivo deste trabalho foi avaliar a frequência da DTM a partir da aplicação do RDC/TMD e a severidade da DTM através do Índice Anamnésico de Fonseca em mulheres com Migrânea, Migrânea Crônica e mulheres sem queixa de cefaleia. Participaram deste estudo 91 mulheres, divididas em três grupos: 30 mulheres no Grupo Controle (GC), 38 mulheres no Grupo Migrânea (GM) e 23 mulheres no Grupo Migrânea Crônica (GMC). As voluntárias dos grupos GM e GMC foram selecionadas durante a primeira consulta no Ambulatório de Cefaleia (ACEF) do Hospital das Clínicas de Ribeirão Preto da Faculdade de Medicina da Universidade de São Paulo e as do GC entre as acompanhantes dos pacientes naquele mesmo dia. Foram inclusas voluntárias com idade entre 18 e 55 anos, que não tivessem ingerido antiinflamatórios e/ou analgésicos nas últimas 24 horas antecedentes à avaliação fisioterapêutica, que não tivesse história de trauma na face, nem usasse prótese dentária parcial ou total e foram excluídas voluntárias com outros tipos de cefaleia e doenças sistêmicas como fibromialgia e artrite reumatóide. Para o GC, as voluntárias não podiam ter queixa de cefaleia nos últimos 3 meses. Três examinadores participaram da coleta. Para análise dos dados foi utilizado a análise da variância (ANOVA two-Way p<0,05) na comparação dos dados antropométricos e da amplitude de movimento mandibular entre os três grupos e Tukey como post-hoc análise para avaliar a diferença no número de locais dolorosos e o número de diagnósticos, com nível de significância de (p<0,05). O teste qui-quadrado foi utilizado para verificar a diferença de diagnóstico entre os três grupos e para verificar a freqüência da severidade entre os três grupos foi utilizado o teste exato de Fisher. As voluntárias dos grupos com migrânea apresentaram maior frequência de diagnósticos de DTM em comparação ao GC, p<0,05 e não foi observada diferença entre os grupos com migrânea. Os diagnósticos, segundo o RDC/TMD, do grupo I (dor miofascial) foram os mais prevalentes nos três grupos estudados e foi mais freqüente nos grupos com migrânea. Os diagnósticos dos grupos I+III estiveram presentes nos três grupos estudados e com maior freqüência no grupo GM. Não foram encontrados diagnósticos individuais pertencentes apenas aos grupos II e III. O número de pontos dolorosos musculares foi significativamente maior nos grupos GM e GMC em relação ao controle e não houve diferença entre os grupos com GM e GMC. As voluntárias dos grupos com migrânea apresentaram maiores graus de severidade de DTM, em comparação ao GC, p<0,05 e o GMC apresentou maior severidade que o GM. Os resultados deste trabalho demonstraram que Mulheres com Migrânea tem maior frequência de DTM, apresentam maior número de diagnósticos e de pontos dolorosos segundo o RDC/TMD que mulheres sem migrânea bem como maiores graus de severidade de DTM. Portanto a DTM e a Migrânea estão clinicamente relacionadas. / Migraine and Temporomandibular Disorders (TMD) are chronic disorders and their most important aspect is the chronic pain. The persistent cranial-cervical and orofacial pain is the predominant reason why people seek treatment. Besides the pain, the affected areas are also similar suggesting an association between these two conditions. Many studies describe signs and symptoms of TMD in patients with headache suggesting an association between these two conditions. However, there are few studies that use a criterion that provides not only signs and symptoms, but also the diagnostic classification. The Diagnostic Criteria for Research in Temporomandibular disorders (RDC / TMD) provide a diagnostic classification with reports of acceptable levels of reliability, provide specifications for the conduct of a clinical standard and allow the development of clinical diagnoses (Axis I), the classification psychosocial classification of the individual (Axis II). The objective of this study was to evaluate the frequency of the DTM from the application of the RDC / TMD and TMD severity through the history index of Fonseca in women with migraine, chronic migraine and women with complaints of headache. The study included 91 women, divided into three groups: 30 women in the control group (CG), 38 women in the migraine group (GM) and 23 women in Chronic Migraine Group (CMG). The voluntary groups GM and GMC were selected during the first appointment and at the Headache Clinic (ACEF) of the University Hospital of Ribeirão Pretos Faculty of Medicine, (University of São Paulo) and the ones of CG were selected among the companions of the patients during that day. There were included volunteers aged between 18 and 55, who had not ingested anti-inflammatory and / or painkillers in the last 24 hours before the physical therapy evaluation and who didnt have a history of face trauma, or wore partial or total dentures and volunteers with other types of headache and systemic diseases such as fibromyalgia and rheumatoid arthritis were excluded. For the GC, the volunteers could not have complained of headache in the last 3 months. Three examiners participated in data collection, I and II in the initial screening of volunteers and III in the implementation of the RDC / TMD and the history index of Fonseca, the examiner III was blind to the conditions of the volunteers and was previously trained. In order to analyze the Data it was used analysis of variance (two-way ANOVA p <0.05) in comparison of anthropometric data and range of mandibular movement between groups and Tukey as posthoc analysis to evaluate the difference in the number of painful sites and the number of diagnoses, with a significance level of p <0.05. The chi-square test was used to determine the difference in diagnosis between the three groups and to determine the frequency of severity among the three groups used the Fisher exact test. The voluntary group with migraine showed a higher frequency of diagnosis and higher severity of TMD in comparison to the CG, p <0.05 and no difference was observed between the groups with migraine.
229

Adaptação transcultural e confiabilidade do questionário 12 item Allodynia Symptom Checklist para o Brasil / Cross-cultural adaptation and reliability of the 12 item Allodynia Symptom Checklist for the Brazilian population

Florencio, Lidiane Lima 22 February 2013 (has links)
O objetivo foi realizar a adaptação transcultural do 12 item Allodynia Symptom Checklist para a população brasileira e testar a confiabilidade dessa versão, já que não havia nenhum questionário de avaliação da alodínia cutânea em migranosos, sintoma que tem sido apontado como sinalizador da sensibilização central e como fator de cronificação dessa doença. A adaptação transcultural foi realizada em seis estágios: tradução, síntese, retrotradução, revisão pelo comitê de especialistas na área, pré-teste e submissão dos documentos ao comitê de especialistas. No estágio do pré-teste, foram aplicados 30 questionários em migranosos de ambos os sexos, que relataram dificuldades de compreensão e, dessa maneira, uma segunda versão foi criada e aplicada em mais 30 sujeitos, para a qual não foram relatadas dificuldades adicionais. O tempo médio de preenchimento foi de 336 e a consistência interna foi considerada adequada demonstrando uma boa correlação entre os itens ( de Cronbach = 0,77). Para testar a confiabilidade, outros 30 sujeitos preencheram o questionário, em dois momentos, sendo que para 15 deles o questionário foi autoaplicável e para os outros 15 a avaliação foi feita no formato de entrevista. A confiabilidade foi classificada como moderada (kappa ponderado linear = 0,58) e excelente ( kappa ponderado linear =0,84) respectivamente. Portanto, foi possível através desse estudo, disponibilizar em língua portuguesa um questionário válido, confiável e de fácil aplicação para a avaliação da alodínia em migranosos da população brasileira. / Since there was no portuguese questionnaire to evaluate cutaneous allodynia in migraine population, which has been pointed out as a central sensibilization flag and as risk factor of migraine chronification we aimed to perform the cross-cultural adaptation of the 12 item Allodynia Symptom Checklist for the Brazilian population and to test its reliability. It consisted in six stages: translation, synthesis, back translation, revision by a specialist committee, pretest, and submission the documents to the committee. In the pretest stage, the questionnaire was applied to 30 migraineurs of both sexes, who had some difficulty in understanding it. Thus, a second version was applied to 30 additional subjects, with no others difficulties being reported. The mean filling out time was 336and the internal consistency was considered adequate showing a good interrelation between items (Cronbachs = 0,77). To test reliability, 30 other subjects filled out the questionnaire at two different times, 15 of them in a self-report administration and 15 in a structured interview. It was classified as moderate (linear weighted kappa = 0.58) and as excellent (linear weighted kappa = 0.84) respectively. In this study, it was possible to make available in portuguese a valid, reliable and easy tool for cutaneous allodynia assessment in Brazil.
230

Genetics of pain : studies of migraine and pain insensitivity

Norberg, Anna January 2006 (has links)
Pain is a major public health issue throughout the world. Increased understanding of the different forms of pain and identification of susceptibility genes could contribute to improved treatments. The main aims of this thesis were to identify the underlying genetic causes of pain by studying two large families affected with migraine and pain insensitivity, respectively. Migraine is one of the most common neurovascular disorders, affecting over 12% of the western population. The genetic contribution to migraine is about 50% according to family and twin studies. To identify novel susceptibility loci for migraine, we performed a genome-wide screen in a large family with migraine from northern Sweden. Linkage analysis revealed significant evidence of linkage (LOD=5.41) on chromosome 6p12.2-p21.1. A predisposing haplotype spanning 10 Mb was inherited with migraine in all affected members of the pedigree. Further fine-mapping of multiple SNP markers restricted the disease critical region to 8.5 Mb. Nine candidate genes were sequenced, revealing no disease-associated polymorphisms in SLC29A1, CLIC5, PLA2G7, IL17, SLC25A27 and TNFRSF21, but rare novel polymorphisms segregating with the disease haplotype in EFHC1, RHAG and MEP1A. EFHC1 has recently been shown to be involved in epilepsy, which is interesting considering the link between migraine and epilepsy. However, association analysis of EFHC1 revealed no difference between patients and controls, suggesting that this gene is not a risk factor for migraine. The combination of the two polymorphisms in RHAG and MEP1A could, however, not be found in any control individuals, indicating that they might be involved in genetic predisposition to migraine in this family. Disorders with reduced pain sensitivity are very rare, since pain perception is essential for survival. A number of disorders have still been identified with pain insensitivity and peripheral nerve degeneration as major clinical signs, including the hereditary sensory and autonomic neuropathies (HSAN). In order to identify novel susceptibility genes for HSAN V, we performed a genome-wide screen in a large consanguineous pedigree from a small village in northern Sweden. A homozygous region identical-by-descent was identified on chromosome 1p11.2-p13.2 in the three most severely affected patients. Subsequent analysis of candidate genes revealed a missense mutation in a conserved region of the nerve growth factor beta (NGFB) gene, causing a drastic amino acid change (R211W) in the NGF protein. NGF is important for the development and maintenance of the sympathetic and sensory nervous system and is therefore likely to be involved in disease. Functional analysis revealed that mutant NGF failed to induce neurite outgrowth and cell differentiation in PC12 cells. Furthermore, almost no mutant NGF was secreted by COS-7 cells, indicating that the processing and/or secretion of the protein might be disrupted. In conclusion, these findings present a novel migraine locus on chromosome 6 and identification of two rare polymorphisms that might be risk factors for migraine. Furthermore, a mutation in NGFB was found to cause complete loss of deep pain perception, which represents a very interesting model system to study pain mechanisms.

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