L’hyperacousie est définie comme une hypersensibilité aux sons d’intensité modérée. Il s’agit d’un trouble de la perception auditive qui a des répercussions néfastes sur la qualité de vie des patients. Un mécanisme impliquerait la modification du gain central des neurones auditifs centraux sous l'influence des régions cérébrales non auditives. Toutefois, la question de l'endroit où ces anomalies surviennent dans le système auditif reste ouverte, plus particulièrement lorsque l'hyperacousie survient sans perte auditive neurosensorielle. Nous avons utilisé un modèle animal d’hyperacousie réversible et sans perte audiométrique, induit par injection aigue de salicylate. Nous avons observé un raccourcissement significatif de la latence des ondes III et IV des PEA aux fréquences inférieures à 10 kHz corrélé à une diminution de 15 dB du seuil de réflexe de sursaut acoustique à basses fréquences. La diminution de l’efficacité du réflexe musculaire de l’oreille moyenne suite à l’injection de salicylate semble trop modérée pour expliquer l'hyperacousie, qui semble plutôt être causée par une altération du codage temporo-spatial de la sonie dans le tronc cérébral. L’hyperacousie fait partie des troubles de perception retrouvés dans la migraine, nous avons étudié les changements physiologiques auditifs dans un modèle animal de migraine induit par administration extradurale de soupe inflammatoire. Dans un contexte migraineux, aucun des paramètres modifiés par le salicylate n'est affecté de sorte que l'hypersensibilité au son est plutôt une phonophobie, réponse émotionnelle au son résultant d’une activation anormale du système limbique et du système nerveux autonome. / Hyperacusis is a disorder of loudness perception defined as decreased tolerance to ordinary environmental sounds that are felt as disagreeable, or even, unbearably painful. The idea that hyperacusis is underpinned by an increase in central auditory gain is now widely invoked. Besides, the neural bases of this gain abnormality remain unclear, as well as more generally the mechanisms of loudness perception. We used an animal model of reversible and hearing-loss-free hyperacusis induced by acute salicylate injection. We observed a significant shortening of the latency of ABR waves III and IV at frequencies below 10 kHz correlated to a 15 dB decrease of the threshold of acoustic startle reflex at low frequencies and without sensorineural hearing loss. The decreased effectiveness of middle ear muscle reflex following salicylate injection seems too moderate for explaining hyperacusis, which is more likely produced by impaired temporo-spatial loudness coding with a brainstem origin. Hyperacusis is one of the perceptual disorders found in migraine. We studied auditory physiological changes in an animal model of migraine induced by extradural administration of inflammatory soup. In a migraine context, none of the salicylate-induced changes was observed so that the reaction to sound is likely closer to phonophobia, an emotional response to sound resulting from abnormal activation of the limbic system and the autonomic nervous system.

Les connaissances actuelles de la physiopathologie de la migraine ne permettent pas encore de déterminer avec exactitude le processus pathologique à lorigine de lactivation du système trigémino-vasculaire conduisant à la céphalée migraineuse. Certains arguments sont en faveur danomalies fonctionnelles du cortex cérébral à même denclencher le processus de la crise de migraine. Parmi ces anomalies, une hypersensibilité sensorielle a été décrite de longue date et a conduit à un important travail en neurophysiologie clinique. Ainsi lutilisation des techniques de potentiels évoqués a abouti à divers résultats dont le plus reproductible consiste en un déficit dhabituation des réponses évoquées corticales lors de stimulations sensorielles répétées chez les migraineux en période intercritique. Comprendre lorigine du déficit dhabituation retrouvé chez les migraineux devrait permettre de préciser le rôle du cortex cérébral dans la cascade dactivation menant à la crise de migraine. Nous avons utilisé la stimulation magnétique transcrânienne répétitive (SMTr) chez les migraineux afin de moduler lexcitabilité des cortex visuel et moteur, en enregistrant ses effets respectivement sur les potentiels évoqués visuels et moteurs. La SMTr a ainsi permis détudier lorigine du déficit dhabituation des potentiels évoqués corticaux retrouvé en période intercritique chez les migraineux. Ce déficit dhabituation des réponses corticales semble provenir dun niveau réduit de préactivation corticale mais également dune activité réduite des interneurones inhibiteurs corticaux. Par ailleurs, ce déficit dhabituation ne semble pas être un élément pathogénique prépondérant dans la mesure où sa seule présence chez les sujets sains ne permet pas den faire des migraineux. Il pourrait correspondre soit à un épiphénomène, soit à un des éléments étiopathogéniques de la migraine, au même titre que la prédisposition génétique, les troubles du métabolisme mitochondrial, Il est vraisemblable que le poids relatif de chacun de ces éléments étiopathogéniques participe à lhétérogénéité des migraines.

Migraine et névralgie du trijumeau sont deux douleurs céphaliques bien différentes, associées à des manifestations allodyniques. Reflétant une sensibilisation centrale, étudier l’allodynie permet de mieux comprendre les mécanismes impliqués dans ces douleurs.- Dans le cas de la migraine: La céphalée est susceptible d’induire par son intensité et sa répétition des modifications profondes du fonctionnement cérébral, conduisant à l’amplification à la fois temporelle (chronicité) et spatiale (allodynie et hyperalgésie extracéphalique) de l’information nociceptive. Les modifications sont durables puisque l’hyperalgésie extra-trigéminale est constante chez le migraineux notamment en période intercritique. Cet état «préallodynique» permanent pourrait être attribuable à une facilitation tonique descendante des informations nociceptives afférentes au niveau de la corne dorsale. L’allodynie qui se développe préférentiellement au cours des crises seraient davantage liée à une altération de l’inhibition descendante corrélée à la fréquence des crises. La mise en jeu des mécanismes inhibiteurs descendant semble être modulable. L’altération des CIDN chez les migraineux est améliorée lorsque des antalgiques/traitements de crise de migraine sont régulièrement consommés. Le sevrage en antalgiques améliore la fréquence des crises mais engendre une re-dégradation des CIDN. L’abus joue donc un rôle promoteur des crises soit via un effet périphérique au niveau des afférences primaires, soit au niveau cortical, mais en tout cas, pas via une altération de la modulation inhibitrice descendante issues des structures du tronc cérébral. - Dans le cas de la névralgie du trijumeau, l’allodynie a des caractéristiques différentes puisqu’elle est très localisée, paroxystique, mécanique et dynamique. Néanmoins la mise en évidence d’une allodynie à tous les modes diffuse au niveau céphalique fait évoque l’existence d’une sensibilisation centrale dans la névralgie du trijumeau. La corrélation qui existe entre abaissement des seuils et nombre de désafférentations d’origine dentaire,amène à envisager que les lésions répétées au niveau des fibres de type C, est à même d’induire des modifications plastiques au niveau de la corne dorsale du sous noyau caudal, permettant alors aux fibres myélinisées de gros calibres, d’accéder aux voies de la nociception, notamment les couches superficielles.Ce facteur serait prédisposant mais pas en lui même un facteur causal suffisant. Une compression nerveuse est plus souvent retrouvée du coté douloureux mais ne semble pas non plus à elle un facteur suffisant pour générer la douleur. La compression nerveuse pourrait contribuer à la pathologie soit via une aggravation de la déafférentation, notamment au niveau des fibres A, soit via un rôle générateur local de potentiels d’action au niveau de ces fibres de gros calibre, ce qui expliquerait qui plus est la disparition très rapide, parfois quasi immédiate de la douleur lorsque les patients subissent une micro-décompression vasculaire. / Migraine and trigeminal neuralgia are two separate cephalic pain characterized by allodynia. Allodynia is of intense interest because it is a way to explore mechanism of pain. Then our work helps to better understanding pathophysiology of these two pain cephalic diseases. -In migraine: During attacks, cutaneous allodynia can extend outside the head involving mosthly thermal modalities. In between attack migraine patients are also characterized by greater extracephalic temporal pain summation and hyperalgesia unrelative to headache frequency or medication intake. Extratrigeminal hyperalgesia and allodynia may be consequence of central sensitization of spinal dorsal horn neurol in relation to tonic descending facilitation of pain. Migraine patients have also impairment of DNIC but in opposite to pain facilitation, DNIC magnitude is changed by several conditions. Loss of DNIC may be driven by repetition of headache and could lead to allodynia extension during attacks. Medication overuse also improves migraine-induced DNIC impairment. Since improvement of DNIC is not able to offset central sensitization, pain facilitation and descending inhibitory input involve two separate and independent ways. Moreover medication overuse may promote the increasing of headache frequency acting on others brain structures than descending pain inhibition. - In trigeminal neuralgia: our current findings promote the possibility that small fibers lesions due to dental deafferentation are predisposing factors for classical trigeminal neuralgia. Patients with CTN have bilateral trigeminal pain hypersensitivity over the trigeminal region, suggesting a central sensitization process. The relationship between pain thresholds and number of dental deafferentations suggest a role of the peripheral input as a driving factor for inducing sensitization. This may have clinical implications in term of the spreading symptomatology, and may promote the development of pain symptoms. In contrast, as for the NVC, the dental deafferentation is only one of several (unknown) conditions that are necessary but not sufficient for trigeminal neuralgia. Even compression could be an aggravating factor of axonal damages; neurovascular contact could be a triggerpromoting excitability of healthy large myelinated fibers.

Background: Migraine is a chronic disaese, often described as a growing publich health problem. One of the suffering groups are adolescents and the prevalence of the migraine is one of the most common reasons why school based health clinics are contacted. The state is related to an extensive, physical and psychological suffering. Objectives: The aim with the presented study was to illuminate the experienced life situation of the adolescent migraineurs. Method: The exploration of articles were done with restriction in databases as Pubmed, CINAHL and psycINFO. The 13 chosen articles were viewed, analyzed and compiled in four different categories with eight sub-categories. Results: The presented outcome reveals that migraine effects the life of adolescents in four different dimensions. The state impacts negatively on the physical and psychological well-being. Furthermore it influences school and leisure of the suffered group. A tendency of isolation and denial is seen as a repeated behaviour in the adolescent migraineurs. Conclusion: Embracement and acceptance ought to be present for the possibility, to create and develop an individual lasting coping strategy. This way of thinking might improve the life situation of the adolescent migraineurs. Keywords: Migraine, adolescents, life changing events, coping strategies, effects. / Bakgrund: Migrän är en kronisk sjukdom och den beskrivs som ett växande folkhälsoproblem. En grupp individer som drabbas är ungdomar och åkomman är en av de vanligaste orsakerna till uppsökt skolvård. Tillståndet är nära bundet till ett omfattande fysiskt och psykiskt lidande. Syfte: Syftet med litteraturstudien var att belysa den upplevda livssituationen hos ungdomar med migrän. Metod: Artiklar har sökts i databaserna Pubmed, CIHNAL och psycINFO och därefter kvalitetgranskats. 13 utvalda artiklar analyserades och sammanställdes i fyra kategorier med åtta underkategorier. Resultat: Resultatet visar att migrän påverkar livet för ungdomar i fyra olika dimensioner. Åkomman påverkar den fysiska och psykiska hälsan negativt och inverkar på ungdomarnas skola och fritid. En tendens av isolering och förnekelse kunde ses som upprepade beteenden. Slutsats: Bemötande och acceptans bör infinnas hos den migränsjuke för att vidare kunna skapa och utveckla en individuellt hållbar copingstrategi som förbättrar livssituationen. Nyckelord: Migrän, ungdomar, livshändelser, copingstrategier, effekt.

This study compared psychological and physiological differences between children diagnosed with migraine and their healthy peers. Physiological measures were obtained at baseline, after discussing an emotionally relevant stressor, and after recovery in 21 children with pediatric migraine and 32 healthy peers. Comparisons were also made on psychological measures investigating sleep problems, anxiety, and family stress. It was hypothesized that children with migraine compared to their peers 1) would report more sleep disturbances, anxiety, and family stress 2) would exhibit greater sympathetic activation at rest, in response to an emotional stressor, and after a recovery period and 3) that autonomic functioning would mediate the relation between the presence of pediatric migraine and sleep disturbances. Results indicated that the migraine group reported significantly greater anxiety compared to peers but there were no significant differences in sleep disturbances or family stress. Within the migraine group, migraine severity was significantly associated with total sleep disturbance and greater incidence of parasomnias, while migraine duration was significantly associated with greater night time awakenings. Migraine children also exhibited a significantly higher pulse rate compared to their peers at rest and a significantly higher diastolic blood pressure and marginally significant higher LF/HF ratio at recovery from an emotional stressor. These findings suggest that sleep disturbance and pediatric migraine are significantly related but the relation is unclear and warrants additional research. Results also indicate that children with migraine may experience more anxiety than peers. Of most interest, results suggest that children with migraine may experience a disinhibition of the autonomic nervous system characterized by a dominance of the sympathetic nervous system resulting in a longer recovery period following an emotional stressor.

Migraine is one of the most common neurological disorders. The pathological conditions that initiate and sensitize afferent pain signaling are poorly understood. The goal of this study is to identify the ion channels and signaling proteins underlying activation and sensitization of meningeal nociceptors.In trigeminal neurons retrogradely labeled from the cranial meninges, approximately 80% responded to a pH 6.0 application with a rapidly activating and desensitizing ASIC-like current. Pharmacological experiments and kinetics analysis demonstrated that dural afferent pH-sensitive currents were mediated via activation of ASIC3. In addition, applications of decreased pH solutions were able to excite these neurons and generate action potentials. In awake animals, application of decreased pH solutions to the dura produced dose-dependent facial and hindpaw allodynia, which was also mediated through activation of ASIC3. Accumulating evidence indicates that meningeal inflammation induced sensitization of dural afferents contributes to migraine headache. We have demonstrated here that in the presence of mast cell mediators, dural afferents showed a decreased pH threshold and increased activity in response to pH stimuli both in vivo and in vitro. These data provide a cellular mechanism by which decreased pH in the meninges directly excites afferent pain-sensing neurons potentially contributing to migraine headache. It also indicates that inflammatory events within the meninges could sensitize afferent pain signaling and result in increased sensitivity of dural afferents.Intracranial Interleukin-6 (IL-6) levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges. Here we reported that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia via activation of the ERK signaling pathway. IL-6 application was also able to increase neuronal excitability in a manner consistent with phosphorylation of Nav1.7. These data provide a cellular mechanism by which IL-6 in the meninges causes sensitization of dural afferents therefore contributing to the pathogenesis of migraine.These findings are discussed in relation to how activation and sensitization of primary afferent neurons might initiate migraine pain signaling and how the research included in this dissertation relates to the development of new therapeutic strategies for migraine.

Migrena - dažnas lėtinis susirgimas, kuris daugiausiai vargina jaunus žmones. Priepuolių metu dėl skausmo ir lydinčių reiškinių yra sutrikdoma ligonių kasdienė veikla. Be to, sergantiems migrena, o ypač migrena su aura, yra 2-3 kartus padidėjusi išeminių insultų, o taip pat kitų išeminių - kraujagyslinių komplikacijų rizika. Darbo tikslas buvo laikotarpyje tarp priepuolių nustatyti moterims, sergančioms migrena su aura (MA) ir be auros (M0), ryšį su bendraisiais kardiovaskulinės rizikos veiksniais, uždegiminių žymenų specifiškumu, ląstelinės hemostazės ypatumais bei su įvairaus diametro periferinių kraujagyslių endotelio funkcijos bei standumo kitimais. Ištyrėme 60 sveikų, 30 sergančių MA ir 30 M0. M0 moterims nustatytas didesnis sistolinis ir diastolinis kraujospūdis bei hipodinamija. Neįrodytos serumo amiloido A ir C reaktyvaus baltymo sąsajos su migrenos tipais, trombocitų funkcinio aktyvumo kitimais bei su įvairaus diametro periferinių kraujagyslių standumo ar endotelio funkcijos sutrikimais. Sergančiosioms migrena buvo padidėjęs trombocitų funkcinis aktyvumas, kuris priklausė nuo migrenos formos, M0 sergančiosioms ir nuo priepuolių dažnio Migrenos grupėje endotelio funkcija buvo sutrikusi tik mikrocirkuliacijoje. MA grupėje buvo didesnė tėkmės sąlygota dilatacija nei M0. Sergančiosioms migrena nustatytas susidarančių trombocitų monocitų agregatų tiesioginis ryšys su kitimais mikrocirkuliacijoje ir atvirkštinis ryšys su endotelio funkcija smulkiosiose periferinėse... [toliau žr. visą tekstą] / Migraine is a common chronic disease that is usually suffered by young people. During the attacks due to pain and other concomitant phenomena everyday activities of the patients are interrupted. Furthermore, people with migraine, especially with migraine with aura, are subject to 2-3 bigger risk of ischaemic stroke, as well as other ischaemc-blood vessel complications. The goal of the thesis is to determine the relation between migraine with aura (MA) and without aura (M0) (in women) and common cardiovascular risk factors, particularity of inflammatory markers, particularities of cellular hemostasis, as well as changes in functionality and stiffness of endothelium of peripheral blood vessels of various diameter during period between the attacks. 60 healthy women, as well as 30 with MA and 30 with M0 participated in the research. Higher systolic and diastolic blood pressure, as well as hypodynamia was registered in the M0 group. The relation between serum amyloid A, C reactive proteine and types of migraine, changes in functional activity of platelets and changes in functionality or stiffness of endothelium of peripheral blood vessels of various diameter was not proved. Women with migraine had an increased functional activity of platelets that depended on the type of migraine, frequency of attack and was more common in women with M0. In the migraine group endothelial function was unbalanced only in microcirculation. MA group demonstrated a higher flow-induced dilation than... [to full text]

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.

Migraine is one of the most prevalent contributors to the global burden of mental and neurological disorders. It is a complex episodic condition that presents as intense recurrent unilateral headaches lasting hours to days that can be accompanied by nausea, photophobia, phonophobia and other neurological symptoms. The causes of migraine appear multifactorial and are not fully understood. However, activation of the trigeminovascular system and sphenopalatine parasympathetic neurons and the resulting vasodilation of meningeal arteries have been associated with the development of migraine pain. Recently, the neurotransmitter and neurotrophic peptide pituitary adenylate cyclase activating polypeptide (PACAP) has been implicated in this migraine headache pathway. The effects of PACAP parallel those of other migraine inducing agents and notably PACAP induces vasodilation of the MMA concurrent with the genesis of migraine headache when administered to human subjects. The mechanisms by which PACAP induces dilation are presently unclear. The objective of this present work was to elucidate the signaling pathways linking PACAP to MMA dilation. To achieve this objective, we developed an ex vivo approach to study isolated MMA at physiologically relevant intravascular pressure. Using this preparation we found that PACAP dilates MMA at picomolar concentrations via PAC1 receptors. Further, in MMA, PACAP-induced dilation is mediated exclusively though activation of KATP channels. While investigating the mechanisms of PACAP-induced dilation of MMA we discovered that basal KATP channel activity influences MMA diameter. Inhibition of KATP channels with glibenclamide or PNU37883 at physiological intravascular pressure resulted in a vasoconstriction of ≈ 20 %. Also consistent with basal KATP activity, glibenclamide induced a membrane potential depolarization of ≈ 14 mV. Further, in MMA loaded with the ratiometric Ca2+ indicator, Fura-2-AM, glibenclamide-induced MMA constriction was correlated with a simultaneous increase in the ratio of 340 nm/380 nm excited fura-2 fluorescence, consistent with an increase in intracellular Ca2+. Vascular smooth muscle KATP channels can be phosphorylated and activated by PKA, resulting in membrane potential hyperpolarization. KT5720, a PKA inhibitor, induced a constriction in MMA similar to that of glibenclamide (≈ 25 %). Additional treatment with glibenclamide did not induce further constriction suggesting that PKA activity may underlie tonic KATP channel activation. Together these results suggest that tonic PKA activity underlies basal KATP channel activity and together play a key role in regulation of MMA diameter. In summary, results presented in this dissertation suggest that picomolar PACAP-induced dilation of MMA is via activation of the PAC1-Hop1 receptor splice variant and KATP channel activation. Furthermore, KATP channels are also involved in tonic regulation of MMA diameter due to basal PKA activity. These unique features of the MMA provide additional insight into potential therapeutic targets in the development of treatments for migraine.

DIPLOMA THESIS: The impact of acupuncture on heart rate variability in patients with migraine SOCIAL AND CLINICAL PHARMACY DEPARTMENT, FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ, CHARLES UNIVERSITY IN PRAGUE AUTHOR: Kateřina Jehličková SUPERVISOR: PharmDr. Jitka Pokladníková, Ph.D. INTRODUCTION: Migraine is one of the most common diseases that affects up to 25% of human adult worldwide. The popularity of alternative therapeutic method is increasing, in this case namely acupuncture, currently between 11-46% globally, 4-9,9% respectively. OBJECTIVE: The primary goal of this work is to evaluate if acupuncture has any effect on HRV in patients with migraine. Secondary goal is to find out which psychosocial factors may influance HRV parameter changes. METHODOLOGY: HRV measurment was performed before acupuncture and after 12 weeks of acupuncture therapy. At first, results were processed in KUBIOS software which is specially designed for the study of heart rate variability and the needed parameters. Then the statistical analysis of a paired t-test (p=0,05) and linear regression (p=0,1) were done in SPSS software. MIDAS questionnaire (quality of life in patients with migraine), life satisfaction questionnaire (Satisfaction with Life Scale, SWLS) and The Symptom Checklist (SCL-90) were used to determine factors...