Le maintien d'un potentiel de membrane de repos négatif est à la base de l'excitabilité neuronale. Ce potentiel négatif est généré par un courant de fuite de potassium induit par les canaux potassiques à deux domaines pore (K2P). Ils se sont révélés impliqués dans de nombreux mécanismes physiologiques et physiopathologiques tels que la dépression, la neuroprotection contre les ischémies, l'anesthésie, la migraine et la perception de la douleur. L'hétéromultimérisation est un mécanisme couramment utilisé dans la nature pour augmenter la diversité fonctionnelle des complexes protéiques. Par exemple, avec 15 gènes classés en 6 sous-familles, les canaux K2P pourraient générer 120 combinaisons et, en théorie, chacune d’elles possèderait des caractéristiques bien distinctes. Ici, nous avons d’abord étudié la capacité des membres de la même sous-famille K2P (sous-famille TREK) à s’assembler pour former des hétéromères fonctionnels dotés de nouvelles propriétés. En alliant l’optopharmacologie, une technique de précipitation de molécules uniques (SiMPull) et une technique de co-localisation à l’échelle de la molécule unique à la membrane plasmique, nous avons déterminé l’existence ainsi que la stœchiométrie des complexes créés entre TREK1, TREK2 et TRAAK. Nous avons caractérisé fonctionnellement les hétérodimères et avons constaté qu'ils formaient tous des canaux sélectifs au potassium rectifiant vers l'extérieur avec une sensibilité à la tension et aux pH variables. Ayant constaté que l’hétéromérisation est possible dans la même sous-famille, nous nous demandons si cela peut être fait entre membres de familles différentes et quelles pourraient en être les conséquences pathophysiologiques. Nous avons trouvé que TREK1 et TREK2 sont capable d’hétéromériser avec le canal plus distant TRESK, un canal K2P impliqué dans la migraine. Chez l'homme, la mutation TRESK-MT, une délétion de 2 paires de base (F139WfsX24) qui induit la formation de TRESK-MT1, un dominant négatif de TRESK, a été corrélé à la migraine. De manière surprenante, nous avons découvert que cette délétion induit un site alternatif de traduction (fsATI), menant à la formation d’un second fragment de TRESK, TRESK-MT2 qui s’assemble spécifiquement avec TREK1 et TREK2. Cet assemblage induit l’extinction des courants TREK, ce qui va augmenter l’excitabilité des neurones trijumeaux, une composante clé dans l’induction de la migraine, à l’origine du phénotype migraineux observé. Ensemble, ces résultats démontrent que l’hétéromérisation des canaux K2P n’est pas rare et doit être considérée pour comprendre leurs fonctions pathophysiologiques. Enfin, les analyses génétiques des mutations liées à des pathologies devraient désormais prendre en compte les fsATI. / Maintenance of a negative resting membrane potential underlies the basis of neuronal excitability. This negative potential is generated by a potassium leak current mediated by two-pore-domain potassium channels (K2P). Over the years, they have been shown to be involved in many physiological and pathophysiological mechanisms such as depression, neuroprotection, anesthesia, migraine and pain perception. Heteromultimerization is a mechanism commonly used to increase the functional diversity of protein complexes. For example, with 15 genes classified in 6 subfamilies, the K2P channel family can potentially generates 120 combinations and, in theory, each of them would show different functional properties. Here, we first investigated the ability of the members from the same K2P subfamily (TREK subfamily) to assemble and form functional heteromeric channels with novel properties. Using single molecule pulldown (SiMPull) from HEK cell lysates, subunit counting in the plasma membrane of living cells and opto-pharmacology, we show that the TREK channel members TREK1, TREK2, and TRAAK readily co-assemble. We functionally characterized the heterodimers and found that all combinations form outwardly rectifying potassium-selective channels but with variable voltage sensitivity and pH regulation. Having found that heteromerization is possible within the same subfamily we wonder if it can happen between members from different subfamilies with lower sequence homology and what could be the pathophysiological consequences. We found that TREK1 and TREK2 are able to heterodimerize with the distantly-related TRESK, a two-pore-domain K+ channel implicated in migraine. Notably, in humans, TRESK-MT, a 2 bp frameshift mutation (F139WfsX24), which induced the formation of TRESK-MT1 a dominant negative for TRESK, was found to perfectly segregate with typical migraine in a large pedigree. Strikingly, we found that the 2 bp frameshift mutation induced an alternative translation initiation (fsATI) which leads to the translation of a second TRESK fragment, termed TRESK-MT2. We show that by co-assembling with and inhibiting TREK1 and TREK2, TRESK-MT2 increases trigeminal sensory neuron excitability, a key component of migraine induction, leading to a migraine-like phenotype. Together these findings demonstrate that K2P heteromerization is not rare and needs to be considered to understand their pathophysiological functions and that genetic analysis of disease-related mutations should consider fsATI as a distinct class of mutations.

After an initial four week baseline period, during which headache activity and medication consumption were monitored, 28 migraineurs were randomly assigned to one of the following groups: (a) the biofeedback temperature warming group, (b) the visual imagery group, (c) the combined treatment group, or (d) the comparison group. All four groups continued to monitor their headache activity and medication consumption during the eight week treatment period and the eight week follow-up period. A two way analysis of variance computed on groups over time indicated a significant decrease in headache activity and medication consumption. During the follow-up period (a) the combined treatment group had significantly fewer headaches than the biofeedback group or the comparison group and (b) the visual imagery group and the combined treatment group had significantly fewer headache hours than the biofeedback group or the comparison group. These results do not appear to be attributable to differences between groups on the amount of time spent in home practice or subjective ratings of relaxation. There was no consistent relationship between increases in finger temperature and headache activity improvement. Decreases in powerful other scores, as measured by the Health Attribution Test, and increases in subjective ratings of internal control were consistent with a reduction in headache activity and medication consumption.

Doctorat en kinésithérapie et réadaptation / info:eu-repo/semantics/nonPublished

Le but de l'étude était d'évaluer le rôle de Pautorégulatlon de la température dans le traitement de la migraine par la rétroaction biologique thermique en la comparant à une procédure tout aussi crédible mais qui ne provoquerait aucun effet significatif sur la température des mains. Vingt-quatre femmes migraineuses ont été assignées à l'une ou l'autre des deux conditions suivantes: la rétroaction biologique thermique ou le TENS (ou stimulation électrique transcutanée). Cette dernière était appliquée de façon à maximiser les attentes thérapeutiques et à minimiser les effets sur la température des mains. La manipulation expérimentale s'est avérée un succès. Cependant, aucune des différences observées entre les groupes au niveau des effets thérapeutiques n'était significative. Il en est de même des corrélations qui furent effectuées entre les changements de température au niveau de la main et l'amélioration thérapeutique. Ainsi, l'hypothèse selon laquelle l'efficacité de la rétroaction biologique serait médiée par l'autorégulation de la température n'est pas supportée dans cette étude.

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Cette étude vise à identifier les principaux facteurs psychologiques associés à la prise d'une médication de type analgésique, chez les personnes souffrant de maux de tête récurrents. L'échantillon se compose de quarante-deux personnes souffrant de maux de tête de type migraine (N =19) et de céphalées d'origine médicamenteuse (N = 23). Ces personnes sont recrutées dans des cliniques spécialisées dans le traitement des maux de tête et par le biais d'annonces diffusées dans les journaux. Les participants répondent à un ensemble de questionnaires et complètent un journal d'auto-enregistrement quotidien pendant cinq semaines. Par la suite, les participants sont classés en deux groupes selon leur diagnostic de maux de tête. Les résultats ne révèlent aucune différence significative entre les groupes sur les variables psychologiques. Toutefois, des analyses de régression indiquent que l'âge, le nombre de jours de maux de tête et la perception de l'efficacité personnelle sont associés à la prise d'analgésiques narcotiques.

Migraine - with or without aura - is an enervating primary headache disorder that represents a heavy economic and social burden. The health-related quality of life of migraineurs is poor. The aim of this research was to investigate the health-related quality of life of migraine without aura sufferers. As the thesis was approached from a biopsychosocial perspective, potential determinants were chosen for investigation from the molecular, individual, interpersonal and wider societal levels. The research was executed in two phases: Phase 1 data (N = 341) were gathered using a survey of health-related quality of life (Short Form 6), temperament (the Tridimensional Personality Questionnaire), catastrophizing as a pain coping strategy (the four-item Pain Coping Scale) and the amount of perceived social support (the six-item Social Support Questionnaire). For phase 2, participants were requested to provide blood specimens for ELISA serum quantification of glutamate (n = 66) and gene expression analysis of the main glutamate transporter gene SLC1A2 on real-time reverse-transcription polymerase chain reaction (n = 20). Of the 341 adult residents of Gauteng Province, South Africa that participated in the survey, 94 (28%) met the criteria for migraine without aura and a further 60 (18%) suffer from possible migraine without aura, using the International Classification of Headache Diagnosis (2nd edition) criteria. This indicates that migraine without aura is a significant burden for South Africa. Health-related quality of life was significantly poorer for migraineurs versus those without migraine (p < .001), and is in fact comparable to that of liver transplant, cardiac bypass and elderly populations. This raises concerns about the severe burden of the disease on the mental and physical well-being of South African sufferers. Investigation of the predictors of health-related quality of life yielded two significant variables when controlling for sex, head and neck injury and language - Harm Avoidance and vii Catastrophizing. The regression model accounts for 29% of the variance in health-related quality of life. A reciprocal relationship likely exists between Harm Avoidance and Catastrophizing, in which a harm avoidant migraineur interprets the headache pain as a catastrophic event to be avoided – even at high cost to the self. Though there have been calls for more biopsychosocial studies of migraine, this thesis did not find added understanding of health-related quality of life through the combination of biological and psychosocial data. The implication is that the role of glutamate in migraine without aura still requires further investigation. Further study is also required with regard to which biological factors may influence the sufferer’s quality of life. The thesis indicates a key role for psychological intervention in aiding migraineurs to live a life of quality. The inclusion of interventions for the psychological aspects of migraine may yield improved outcomes for patients. However, Gauteng residents suffering from MO are potentially unaware of their diagnosis and therefore of potential management for their disorder. Awareness around migraine needs to be the first step in limiting this disorder’s devastating impact on individuals, their relationships and their potential to contribute meaningfully to society. / Psychology / D.Litt. et Phil. (Psychology)

Migraine is ranked as the third most widespread disease in the world by Global burden of Disease and study 2010. To reduce pressure on health care and also help patientsunderstand their condition, mobile health applications have become increasingly popularand accessible. These applications help by providing disease information, to documentsymptoms and analyze attack patterns. However, there is both a lack of patient centeredperspective and scientific based knowledge behind the design of these applications. Therefore, the aim of this study is to explore what might affect the patients’ motivationto use a mobile application to explore their condition. This by looking into how these applications can be designed so that patients’ find them helpful and easy to use. This wasdone by doing a qualitative interview study with ten patients with severe migraine andanalyzing the transcribed data through a reflexive thematic analysis. The thematic analysis resulted in three overarching themes personal motivations of exploring migraine, healthcare related motivations of exploring migraine, and technical support for motivation of exploringmigraine. Each overarching theme contained themes and sub-themes that are backed up byquotes in the data from the interviews. Also a proposal on how to visualize the threeoverarching themes in relation to each other is presented.In conclusion, designing applications that help with acceptance of condition, adaptivecontent and functionality, and deciding on a specific target patient group, are central findings of this study. Directives from health care was found to be the largest motivationaldrive in this study and could further be explored to work better with migraine applications.

Background: Sensitization to sensory stimuli is an essential feature of migraine attacks. The relationship between the clinical course of migraine and increased sensitivity to olfactory stimuli has been little studied so far. - Methods: We analyzed the frequency and quality of osmophobia depending on the phase of migraine in patients with episodic and chronic migraine treated in an tertiary headache center with regard to gender, age, medical history and migraine disability assessment score (MIDAS). Standardized diagnostic questions were used for the assessment of osmophobia. - Results: In our cross-sectional investigation (n = 113), 38.1% of the patients showed an increased preictal hypersensitivity to odors, whereas 61.9% described ictal and 31.9% interictal hypersensitivity to odors, odor-triggered migraine was described in 30.1%. Median migraine disease duration has been statistically significantly longer in patients who suffered from interictal hypersensitivity to odors (28.5 years vs. 20 years; p = 0.012). There was a significant correlation between interictal hypersensitivity and higher age (54.50 vs. 45; p = 0.015). Patients with higher migraine disability in MIDAS experienced more frequently preictal and interictal olfactory sensitization and odor triggered migraine attacks. - Conclusions: In patients with longer migraine disease duration and higher migraine-related impairment, osmophobia was more frequently observed. These results might support the hypothesis of increasing sensitization with increasing burden of migraine.

Bakgrund: Uppkomsten till migrän är inte klarlagd och därav har barriärer uppkommit som försvårar behandling och omvårdnad. Barn och ungdomar är en utsatt grupp då deras utveckling kan påverkas både fysiskt, emotionellt, socialt och i skolan. Syfte: Att beskriva hur livskvalitet hos barn och ungdomar påverkas av migrän. Metod: I denna allmänna litteraturstudie har tio empiriska studier granskats med avseende på kvalitet och innehåll gällande domänerna i livskvalitet. Litteratursökning har genomförts i  EBSCO Discovery Service och CINAHL Complete. Resultat: Migrän påverkar barn och ungdomars livskvalitet negativt både fysiskt, emotionellt, socialt och i skolan. Smärtan har en inverkan på deras dagliga aktiviteter samt ger dem en känsla av oro, nedstämdhet och ångest. Även deras sömn påverkas. Migränen gör det svårt att komma överens och hålla jämna steg med familj och vänner, både i skolan och på fritiden. Slutsats: Studien bidrar med kunskap om hur barn och ungdomars livskvalitet påverkas av migrän. Kunskap hos allmänheten överensstämmer inte med hur barn och ungdomar upplever migrän. Vidare forskning behövs därav beträffande bemötande/behandling av barn och ungdomar med migrän. / Background: The origin of migraine is unclear and therefore barriers which complicate treatment and nursing have arisen. Children and adolescents is a vulnerable group because their development may be affected physically, emotionally, socially and in school. Aim: To describe how the quality of life in children and adolescents is affected by migraine. Method: In this general literature study have ten empirical studies been examined in terms of quality and content of existing domains of quality of life. The literature search has been made in EBSCO Discovery Service and CINAHL Complete. Results: Migraine affects children’s and adolescents’ quality of life negatively both physically, emotionally, socially and in school. The pain has an impact on their daily activities as well as giving them a sense of worry, depression and anxiety. Even sleep is affected. Migraine makes it difficult to get along and keep up with family and friends, both at school and in leisure. Conclusion: This study contributes to knowledge about how children’s and adolescents’ quality of life is affected by migraine. Knowledge in general does not conform with children’s and adolescents’ experience of migraine. Further research is needed regarding the attitudes/treatment towards migraine.