The ability to perceive the Earth's magnetic field has been demonstrated in a variety of animals, including representatives of all five classes of vertebrates. The physiological mechanisms underlying magnetic field sensation, however, remain largely unknown. Behavioral, physiological, neuroethological studies and studies using early response genes as neuronal activation markers indicated that a major role in the perception and processing of magnetic information play trigeminal, vestibular and visual systems. Subsequently, magnetic information seem to be integrated with multimodal sensory and motor information within the hippocampal-entorhinal system. In the majority of studies, however, birds have been used as model organisms. In this work I analyzed the neural substrate of magnetic compass orientation in the mouse strain C57BL/6J using markers c-Fos and Egr1. I found that all the aforementioned systems contain neurons responsive to the experimental magnetic fields. This finding demonstrates a complex processing of the magnetic information at level of the central nervous system.

Neuralgia pós-herpética trigeminal (NPH), neuralgia idiopática do trigêmeo (NIT) e síndrome da ardência bucal (SAB) são doenças neuropáticas da face, caracterizadas por dor na ausência de sinais que evidenciem a causas. Este estudo teve por objetivos determinar as características sensitivas, olfativas, gustativas e salivares em doentes com NPH, NIT e SAB comparados a controles. Foram avaliados 20 doentes de cada grupo, diagnosticados de acordo com critérios da International Association for the Study of Pain (IASP), e 60 indivíduos saudáveis, através de um protocolo sistematizado que incluiu os seguintes testes quantitativos sensitivos: limiares térmicos (frio e calor), limiares mecânicos tácteis, limiares dolorosos de superfície, limiares gustativos (doce, azedo, salgado e amargo), limiares olfativos e fluxo salivar. Os testes foram realizados no território de inervação trigeminal. Os dados foram analisados através dos testes estatísticos ANOVA 1 fator, Tukey, Kruskal-Wallis e Dunn, e o nível de significância foi de 5%. Os limiares térmicos de frio foram diferentes (maiores) somente no ramo mandibular dos doentes com NPH (p=0,001) e os limiares térmicos de calor foram diferentes (maiores) em todos os ramos trigeminais nos doentes com NPH e SAB (p=0,001); a sensibilidade mecânica táctil estava alterada no ramo mandibular de doentes com NPH (p=0,001) e em todos os ramos trigeminais dos doentes com SAB (p= 0,001; p=0,004 e p=0,001); os limiares gustativos salgado e doce, além do limiar olfativo, foram maiores em todos os doentes quando comparados aos controles (p=0,004; p=0,001 e p=0,0389); o sabor ácido obteve os menores limiares e não foram encontradas diferenças para a identificação do sabor amargo ou na avaliação salivar quantitativa (p=0,1694 e p=0,001). Este estudo apresentou evidências de anormalidades sensitivas nos doentes com dor neuropática trigeminal, tanto somestésicas como gustativas e olfativas. A sensibilidade somatosensitiva apresentou-se mais alterada nos doentes com NPH e SAB quando comparados a NIT e aos controles. Mecanismos periféricos e centrais relacionados à percepção e modulação sensitiva podem estar envolvidos na fisiopatologia dos achados aqui observados / Trigeminal postherpetic neuralgia (PHN), idiopathic trigeminal neuralgia (ITN) and burning mouth syndrome (BMS) are painful neuropathies with no clear signs about their causes. The objectives of this study were to determine somatosensory, olfactory, gustative and salivary characteristics of patients with PHN, ITN and BMS compared to controls. Twenty patients from each group, diagnosed according to the criteria from the International Association for the Study of Pain (IASP), and 60 healthy controls were evaluated with a systematized quantitative approach which included thermal (cold and warm), mechanical (tactile), pain, gustative (sweet, sour, salty and bitter) and olfactory thresholds, and quantitative salivary flow evaluation. Data were analyzed with ANOVA 1 factor, Tukey, Kruskal-Wallis and Dunn tests with a level of significance of 5%. Thermal thresholds for cold were different (higher) only in the mandibular branch of patients with PHN (p=0.001) and warm thresholds were higher in all trigeminal branches of PHN and BMS (p=0,001); tactile mechanical sensitivity was altered at the mandibular branch of PHN (p=0,001) and in all trigeminal branches of BMS (p= 0,001; p=0,004 e p=0,001). The salty, sweet and olfactory thresholds were higher in all studied groups (p=0,004; p=0,001 e p=0,0389); the sour threshold was lower and there were no differences in bitter taste or salivary flow (p=0,1694 e p=0,001). This study showed evidences of somatosensory, gustative and olfactory abnormalities in patients with neuropathic orofacial pain. Somatosensory findings were discrete in ITN and more common in PHN and BMS. Peripheral and central mechanisms of perception and modulation could be involved in the physiopathology of these findings

A dor crônica envolve complexos processos de gênese e condução neural e é decorrente da ativação de mecanismos periféricos e centrais de manutenção. Muitos pacientes crônicos são refratários aos diferentes tipos de tratamento propostos, o que gera a suspeita de que de alguma maneira estes não estão sendo totalmente eficazes. O objetivo deste trabalho é avaliar os mecanismos de condução, manutenção e modulação da dor em diferentes condições dolorosas crônicas. Foram avaliadas 92 mulheres, divididas em 5 grupos: Grupo I, 20 pacientes com Dor Miofascial da musculatura mastigatória; Grupo II, 20 pacientes com Fibromialgia; Grupo III, 20 pacientes com Cefaleia Crônica Diária; Grupo IV, 12 pacientes com Neuralgia Trigeminal e Grupo V, 20 pacientes saudáveis assintomáticas. Foram aplicados dois questionários, o IDATE e o OHIP-30, para mensuração do estado ansioso e da qualidade de vida relacionada a condição dolorosa diagnosticada, respectivamente. Todas as pacientes foram submetidas a Testes Quantitativos Sensoriais, como: Limiar de Dor à Pressão, Limiar de Detecção Mecânico, Limiar Doloroso Mecânico, Tolerância à Dor Isquêmica, Sensibilidade Dolorosa ao Frio, Sensação Pós-Estímulo e Controle da Modulação da Dor. Além disso, um Teste Eletrodiagnóstico, que determinou o Limiar de Percepção Atual, através do uso do aparelho Neurometer CPT/C (Neurotron®) foi realizado. Foram avaliadas 3 regiões em cada paciente: trigeminal, cervical e extratrigeminal. Os dados obtidos foram submetidos à análise estatística (ANOVA, Tukey, t-Student) adotando-se um nível de significância de 5% para todos os testes. Todos os grupos experimentais apresentaram altos níveis de ansiedade e grande comprometimento da sua qualidade de vida, quando comparados ao controle. Os Grupos I, II e III apresentaram valores de Limiar de Dor à Pressão significativamente menores do que o Grupo V. As mulheres do Grupo III apresentaram Limiar de Detecção Mecânico significativamente maior do que o Grupo V. Os Grupos I, II, III e IV apresentaram valores de Limiar de Doloroso Mecânico e Tolerância à Dor Isquêmica estatisticamente menores do que o Grupo V. A capacidade de ativação do mecanismo de modulação endógeno, avaliada pelo teste de Controle de Modulação da Dor, está comprometida nas mulheres com Dor Miofascial e Fibromialgia. Não houve diferença estatisticamente significante no Limiar de Percepção Atual (CPT) entre os Grupos I, II, III e V. Pacientes do Grupo IV apresentaram CPT para a frequência de 5Hz significativamente menor do que as do Grupo V na região trigeminal, indicando uma hiperestesia de origem inflamatória no nervo trigêmeo, caracterizando-se a dor neuropática. Ainda, de acordo com os resultados encontrados, os Grupos I, II e III parecem dividir um mecanismo de dor e etiologia semelhantes, não apresentando danos às estruturas neurais e sim uma alteração no processamento e modulação do impulso nociceptivo, caracterizando-se uma dor disfuncional. Os resultados deste estudo mostraram evidências da presença do processo de sensibilização central e prejuízo no mecanismo de modulação endógeno em pacientes com Dor Miofascial, Fibromialgia e Cefaleia Crônica Diária. / Chronic pain involves complex processes of genesis and neural conduction due to activation of peripheral and central mechanisms of pain maintenance. Many chronic patients are refractory to different types of treatment, which leads to the suspicion that somehow they are not fully effective and probably some mechanism of pain generation and/or maintenance is still unknown. Based on that, the aim of the present study is to evaluate the mechanisms of conduction, maintenance and pain modulation in patients with different types of chronic pain conditions. Ninety two women were evaluated, divided into 5 groups: Group I, 20 patients with Myofascial Pain of the masticatory muscles; Group II, 20 patients with Fibromyalgia; Group III, 20 patients with Chronic Daily Headache; Group IV, 12 patients with Trigeminal Neuralgia and Group V, 20 healthy asymptomatic patients. Two questionnaires were used, the STAI and the OHIP-30, to measure state anxiety and quality of life related to painful condition diagnosed, respectively. All patients underwent Quantitative Sensory Tests such as: Pressure Pain Threshold, Mechanical Detection Threshold, Mechanical Pain Threshold, Ischemic Pain Tolerance, Cold Pain Sensitivity, After- Sensation and Control Pain Modulation. An Electrodiagnostic Test, the Current Perception Threshold, using the apparatus Neurometer CPT/C (Neurotron®) was also performed. Three different regions were evaluated for each patient, for each test: trigeminal, cervical and extratrigeminal. Data were gathered and subjected to statistical analysis (ANOVA, Tukey, t-Student), adopting a significance level of 5% for all tests. All patients had high levels of anxiety and greater impairment of their quality of life, when compared to controls. Groups I, II and III showed significantly lower values of Pressure Pain Threshold than Group V. Group III had a significantly higher Mechanical Detection Threshold than Group V. Groups I, II, III and IV showed statistically lower values for Mechanical Pain Threshold and Ischemic Pain Tolerance than Group V. The ability to activate the mechanism of endogenous modulation, evaluated with the Controled Pain Modulation test, is impaired in women with Fibromyalgia and Myofascial Pain. There was no significant differences in the Current Perception Threshold (CPT) between Groups I, II, III and V. Group IV showed a CPT to 5 Hz frequency significantly lower than Group V for the trigeminal region, indicating an hyperesthesic condition due to inflammation of the trigeminal nerve, characterizing neuropathic pain. According to the results, Groups I, II and III seem to share a common pain mechanism and similar etiology, with no significant damage to neural structures but a change in the processing and modulation of nociceptive stimuli, characterizing a dysfunctional pain. The results of this study showed evidence of the presence of central sensitization process and impaired endogenous modulation system in patients with Myofascial Pain, Fibromyalgia and Chronic Daily Headache.

A dor crônica envolve complexos processos de gênese e condução neural e é decorrente da ativação de mecanismos periféricos e centrais de manutenção. Muitos pacientes crônicos são refratários aos diferentes tipos de tratamento propostos, o que gera a suspeita de que de alguma maneira estes não estão sendo totalmente eficazes. O objetivo deste trabalho é avaliar os mecanismos de condução, manutenção e modulação da dor em diferentes condições dolorosas crônicas. Foram avaliadas 92 mulheres, divididas em 5 grupos: Grupo I, 20 pacientes com Dor Miofascial da musculatura mastigatória; Grupo II, 20 pacientes com Fibromialgia; Grupo III, 20 pacientes com Cefaleia Crônica Diária; Grupo IV, 12 pacientes com Neuralgia Trigeminal e Grupo V, 20 pacientes saudáveis assintomáticas. Foram aplicados dois questionários, o IDATE e o OHIP-30, para mensuração do estado ansioso e da qualidade de vida relacionada a condição dolorosa diagnosticada, respectivamente. Todas as pacientes foram submetidas a Testes Quantitativos Sensoriais, como: Limiar de Dor à Pressão, Limiar de Detecção Mecânico, Limiar Doloroso Mecânico, Tolerância à Dor Isquêmica, Sensibilidade Dolorosa ao Frio, Sensação Pós-Estímulo e Controle da Modulação da Dor. Além disso, um Teste Eletrodiagnóstico, que determinou o Limiar de Percepção Atual, através do uso do aparelho Neurometer CPT/C (Neurotron®) foi realizado. Foram avaliadas 3 regiões em cada paciente: trigeminal, cervical e extratrigeminal. Os dados obtidos foram submetidos à análise estatística (ANOVA, Tukey, t-Student) adotando-se um nível de significância de 5% para todos os testes. Todos os grupos experimentais apresentaram altos níveis de ansiedade e grande comprometimento da sua qualidade de vida, quando comparados ao controle. Os Grupos I, II e III apresentaram valores de Limiar de Dor à Pressão significativamente menores do que o Grupo V. As mulheres do Grupo III apresentaram Limiar de Detecção Mecânico significativamente maior do que o Grupo V. Os Grupos I, II, III e IV apresentaram valores de Limiar de Doloroso Mecânico e Tolerância à Dor Isquêmica estatisticamente menores do que o Grupo V. A capacidade de ativação do mecanismo de modulação endógeno, avaliada pelo teste de Controle de Modulação da Dor, está comprometida nas mulheres com Dor Miofascial e Fibromialgia. Não houve diferença estatisticamente significante no Limiar de Percepção Atual (CPT) entre os Grupos I, II, III e V. Pacientes do Grupo IV apresentaram CPT para a frequência de 5Hz significativamente menor do que as do Grupo V na região trigeminal, indicando uma hiperestesia de origem inflamatória no nervo trigêmeo, caracterizando-se a dor neuropática. Ainda, de acordo com os resultados encontrados, os Grupos I, II e III parecem dividir um mecanismo de dor e etiologia semelhantes, não apresentando danos às estruturas neurais e sim uma alteração no processamento e modulação do impulso nociceptivo, caracterizando-se uma dor disfuncional. Os resultados deste estudo mostraram evidências da presença do processo de sensibilização central e prejuízo no mecanismo de modulação endógeno em pacientes com Dor Miofascial, Fibromialgia e Cefaleia Crônica Diária. / Chronic pain involves complex processes of genesis and neural conduction due to activation of peripheral and central mechanisms of pain maintenance. Many chronic patients are refractory to different types of treatment, which leads to the suspicion that somehow they are not fully effective and probably some mechanism of pain generation and/or maintenance is still unknown. Based on that, the aim of the present study is to evaluate the mechanisms of conduction, maintenance and pain modulation in patients with different types of chronic pain conditions. Ninety two women were evaluated, divided into 5 groups: Group I, 20 patients with Myofascial Pain of the masticatory muscles; Group II, 20 patients with Fibromyalgia; Group III, 20 patients with Chronic Daily Headache; Group IV, 12 patients with Trigeminal Neuralgia and Group V, 20 healthy asymptomatic patients. Two questionnaires were used, the STAI and the OHIP-30, to measure state anxiety and quality of life related to painful condition diagnosed, respectively. All patients underwent Quantitative Sensory Tests such as: Pressure Pain Threshold, Mechanical Detection Threshold, Mechanical Pain Threshold, Ischemic Pain Tolerance, Cold Pain Sensitivity, After- Sensation and Control Pain Modulation. An Electrodiagnostic Test, the Current Perception Threshold, using the apparatus Neurometer CPT/C (Neurotron®) was also performed. Three different regions were evaluated for each patient, for each test: trigeminal, cervical and extratrigeminal. Data were gathered and subjected to statistical analysis (ANOVA, Tukey, t-Student), adopting a significance level of 5% for all tests. All patients had high levels of anxiety and greater impairment of their quality of life, when compared to controls. Groups I, II and III showed significantly lower values of Pressure Pain Threshold than Group V. Group III had a significantly higher Mechanical Detection Threshold than Group V. Groups I, II, III and IV showed statistically lower values for Mechanical Pain Threshold and Ischemic Pain Tolerance than Group V. The ability to activate the mechanism of endogenous modulation, evaluated with the Controled Pain Modulation test, is impaired in women with Fibromyalgia and Myofascial Pain. There was no significant differences in the Current Perception Threshold (CPT) between Groups I, II, III and V. Group IV showed a CPT to 5 Hz frequency significantly lower than Group V for the trigeminal region, indicating an hyperesthesic condition due to inflammation of the trigeminal nerve, characterizing neuropathic pain. According to the results, Groups I, II and III seem to share a common pain mechanism and similar etiology, with no significant damage to neural structures but a change in the processing and modulation of nociceptive stimuli, characterizing a dysfunctional pain. The results of this study showed evidence of the presence of central sensitization process and impaired endogenous modulation system in patients with Myofascial Pain, Fibromyalgia and Chronic Daily Headache.

Neuralgia pós-herpética trigeminal (NPH), neuralgia idiopática do trigêmeo (NIT) e síndrome da ardência bucal (SAB) são doenças neuropáticas da face, caracterizadas por dor na ausência de sinais que evidenciem a causas. Este estudo teve por objetivos determinar as características sensitivas, olfativas, gustativas e salivares em doentes com NPH, NIT e SAB comparados a controles. Foram avaliados 20 doentes de cada grupo, diagnosticados de acordo com critérios da International Association for the Study of Pain (IASP), e 60 indivíduos saudáveis, através de um protocolo sistematizado que incluiu os seguintes testes quantitativos sensitivos: limiares térmicos (frio e calor), limiares mecânicos tácteis, limiares dolorosos de superfície, limiares gustativos (doce, azedo, salgado e amargo), limiares olfativos e fluxo salivar. Os testes foram realizados no território de inervação trigeminal. Os dados foram analisados através dos testes estatísticos ANOVA 1 fator, Tukey, Kruskal-Wallis e Dunn, e o nível de significância foi de 5%. Os limiares térmicos de frio foram diferentes (maiores) somente no ramo mandibular dos doentes com NPH (p=0,001) e os limiares térmicos de calor foram diferentes (maiores) em todos os ramos trigeminais nos doentes com NPH e SAB (p=0,001); a sensibilidade mecânica táctil estava alterada no ramo mandibular de doentes com NPH (p=0,001) e em todos os ramos trigeminais dos doentes com SAB (p= 0,001; p=0,004 e p=0,001); os limiares gustativos salgado e doce, além do limiar olfativo, foram maiores em todos os doentes quando comparados aos controles (p=0,004; p=0,001 e p=0,0389); o sabor ácido obteve os menores limiares e não foram encontradas diferenças para a identificação do sabor amargo ou na avaliação salivar quantitativa (p=0,1694 e p=0,001). Este estudo apresentou evidências de anormalidades sensitivas nos doentes com dor neuropática trigeminal, tanto somestésicas como gustativas e olfativas. A sensibilidade somatosensitiva apresentou-se mais alterada nos doentes com NPH e SAB quando comparados a NIT e aos controles. Mecanismos periféricos e centrais relacionados à percepção e modulação sensitiva podem estar envolvidos na fisiopatologia dos achados aqui observados / Trigeminal postherpetic neuralgia (PHN), idiopathic trigeminal neuralgia (ITN) and burning mouth syndrome (BMS) are painful neuropathies with no clear signs about their causes. The objectives of this study were to determine somatosensory, olfactory, gustative and salivary characteristics of patients with PHN, ITN and BMS compared to controls. Twenty patients from each group, diagnosed according to the criteria from the International Association for the Study of Pain (IASP), and 60 healthy controls were evaluated with a systematized quantitative approach which included thermal (cold and warm), mechanical (tactile), pain, gustative (sweet, sour, salty and bitter) and olfactory thresholds, and quantitative salivary flow evaluation. Data were analyzed with ANOVA 1 factor, Tukey, Kruskal-Wallis and Dunn tests with a level of significance of 5%. Thermal thresholds for cold were different (higher) only in the mandibular branch of patients with PHN (p=0.001) and warm thresholds were higher in all trigeminal branches of PHN and BMS (p=0,001); tactile mechanical sensitivity was altered at the mandibular branch of PHN (p=0,001) and in all trigeminal branches of BMS (p= 0,001; p=0,004 e p=0,001). The salty, sweet and olfactory thresholds were higher in all studied groups (p=0,004; p=0,001 e p=0,0389); the sour threshold was lower and there were no differences in bitter taste or salivary flow (p=0,1694 e p=0,001). This study showed evidences of somatosensory, gustative and olfactory abnormalities in patients with neuropathic orofacial pain. Somatosensory findings were discrete in ITN and more common in PHN and BMS. Peripheral and central mechanisms of perception and modulation could be involved in the physiopathology of these findings

No description available.

No description available.

De nombreuses fonctions cérébrales dépendent de la capacité de réseaux de neurones à générer une activité rythmique. Les réseaux neuronaux, nommés générateurs de patron centraux (GPCs), contrôlant les patrons de mouvements répétitifs comme la locomotion, la respiration et la mastication en sont un exemple important. Des travaux antérieurs ont montré que le noyau sensoriel principal du trijumeau (NVsnpr), qui fait partie du GPC de la mastication, contient des neurones qui peuvent décharger de façon rythmique et que les astrocytes et leur protéine S100ß étaient nécessaires pour cette rythmogénèse neuronale. Cependant, l’effet de l’activation directe des astrocytes sur la décharge des neurones du NVsnpr n’a jamais été investigué. De plus, comme les astrocytes forment des réseaux bien définis dans le NVsnpr, nous avons émis l’hypothèse que l’activation de ces réseaux pourrait contribuer à synchroniser l’activité rythmique de groupes de neurones. Pour investiguer ces deux questions, nous avons utilisé des enregistrements en mode cellules entières de neurones et d’astrocytes du NVsnpr lors de stimulations optogénétiques des astrocytes chez des souris transgéniques. Différentes lignées de souris transgéniques ont été utilisées pour exprimer des protéines photosensibles comme la channelrhodopsin (ChR2) ou le récepteur adrénergique α-1 dans les astrocytes du NVsnpr dans le but de pouvoir les stimuler par l’exposition à la lumière. De ces lignées, seul le croisement de souris S100β-Cre à des souris ChR2-lox donna des réponses significatives. Ces résultats démontrent que la stimulation optogénétique des astrocytes du NVsnpr cause divers effets sur la décharge neuronale, dont la genèse de bouffées rythmiques. Cependant, l’enregistrement de paires de neurones n’a pas permis de confirmer l’implication des astrocytes dans la synchronisation de l’activité rythmique des neurones de NVsnpr. Ces résultats permettent d’affiner les méthodes d’études des astrocytes dans le système trigéminal ainsi que de confirmer l’implication des astrocytes dans une activité rythmique, une implication qui pourrait potentiellement être observée dans d’autres structures du système nerveux central comme les GPCs de la locomotion ou de la respiration. / Several cerebral functions depend on the capacity of neural network to generate a rhythmic activity. One prominent example of this is the neural networks, named central pattern generators (CPGs), controlling repetitive movements patterns like locomotion, breathing and chewing. Previous studies have shown that the trigeminal main sensory nucleus (NVsnpr), which is part of the masticatory CPG, contains neurons that can rhythmically discharge and that the astrocytes and their protein, S100β, were essential for this neuronal rhythmogenesis. However, the effect of the activation of astrocytes on neuronal discharge of the NVsnpr remains uninvestigated. Additionally, since astrocytes form well-defined networks in the NVsnpr, we hypothesized that the activation of these networks could help synchronize the rhythmic activity of groups of neurons. To investigate these questions, we used whole cell recordings of neurons and astrocytes of the NVsnpr during optogenetic stimulation of astrocytes in transgenic mice. Different mice strains have been used to express photosensitive proteins such as channelrhodopsin (ChR2) or the α-1 adrenegic receptor in NVsnpr astrocytes to enable their stimulation with light. Of all these strains, only the S100β-Cre X ChR2-lox hybrids provided significant responses. Optogenetic stimulation of NVsnpr astrocytes produced various effects on neuronal discharge, including the genesis of rhythmic bursts. However, the recording of pairs of neurons did not confirm the involvement of astrocytes in the synchronization of the rhythmic activity of NVsnpr neurons. These results contribute to the refinement of methods used to study astrocytes in the trigeminal system and confirm the involvement of astrocytes in rhythmogenesis, an involvement that could be observed in other structures of the central nervous system such as the CPGs for respiration or locomotion.

Le trouble de l’odorat est un symptôme fréquent bien connu de la Maladie de Parkinson (MP). Il apparaît plusieurs années avant la possibilité d’un diagnostic de la maladie et son étude est ainsi d’intérêt particulier pour aider au développement d’outils de dépistage précoces et la sélection de candidats pouvant participer à des essais cliniques visant le développement de traitements potentiellement curateurs. Pour ce faire, il est important de différencier un trouble de l’odorat associé à la MP d’autres troubles de l’odorat non reliés à une maladie neurodégénérative (trouble de l’odorat non-parkinsonien : TONP), tels que des troubles de l’odorat liés à une infection virale, à un traumatisme craniocérébral ou des troubles sinu-nasaux. Le système olfactif est plus complexe qu’il ne le semble et est intimement lié au système trigéminal, un système moins bien connu, qui permet, entre autres, la perception de sensations de fraicheur, chaleur et picotement des odeurs. L’interaction entre les systèmes olfactif et trigéminal est complexe et peu connue. La sensibilité trigéminale est typiquement réduite dans le cas d’un système olfactif altéré dans les TONP, mais il n’est pas bien compris comment les deux systèmes interagissent ensemble dans le cas d’un trouble de l’odorat associé à la MP. L’objectif principal de cette thèse visait donc la caractérisation du trouble de l’odorat associé à la MP lorsque spécifiquement comparé à des patients atteints de TONP. Par conséquent, cette thèse avait aussi pour objectif d’apporter une meilleure compréhension de l’interaction entre les systèmes olfactif et trigéminal dans le cas d’un système olfactif fonctionnel et d’un système olfactif altéré dans la MP et d’autres TONP. Nous avons donc d’abord évalué la sensibilité olfactive et trigéminale, sur le plan comportemental (étude 1). Cette première étude a permis d’identifier un patron de réponse spécifique dans la MP avec un système olfactif altéré et un système trigéminal intact,en comparaison à des contrôles, en contraste à une sensibilité trigéminale réduite dans les TONP. Dans le même ordre d’idée, nous avons ensuite évalué la perception des dimensions trigéminales et olfactives de différentes odeurs (étude 2). Nos résultats suggèrent que la perception de sensations trigéminales est intacte chez les patients avec la MP en contraste à la perception de dimensions olfactives qui est réduite, comparativement à des contrôles. Pour mieux comprendre l’interaction entre le système olfactif et trigéminal dans le cas d’un système olfactif fonctionnel, nous avons ensuite évalué l’impact d’un stimulus olfactif sur la capacité à latéraliser un stimulus trigéminal chez des participants contrôles (étude 3). Cette étude a démontré un effet d’amplification de la réponse trigéminale lors d’une co-stimulation olfactive ipsilatérale suggérant ainsi une interaction au niveau de l’épithélium nasal. Afin de mieux comprendre la réponse trigéminale dans la MP, nous avons évalué la sensibilité trigéminale périphérique et centrale en réponse à un stimulus trigéminal pur via des mesures électrophysiologiques (étude 4). Nous avons ainsi démontré une altération spécifique de la réponse trigéminale dans la MP comparativement à d’autres TONP et à des contrôles. Puisque le bulbe olfactif est l’une des premières régions affectées dans la MP, nous avons ensuite mesuré le volume du bulbe olfactif sur des images IRM (étude 5). Nos résultats ont démontré un volume réduit dans la MP et les TONP comparativement à des contrôles, mais aucune différence entre les patients atteints de la MP et de TONP. Néanmoins, l’utilisation de techniques d’apprentissage profond sur les images IRM du bulbe olfactif a permis de différencier les patients avec la MP des TONP avec une exactitude considérable. Enfin, nous avons étudié la connectivité fonctionnelle au sein du réseau chimiosensoriel (étude 6). Nous avons ainsi identifié des altérations spécifiques de la connectivité et la modularité des réseaux entre des régions de traitement olfactif et trigéminal au repos et lors de la réalisation d’une tâche olfactive et d’une tâche trigéminale chez des patients atteints de la MP en comparaison avec des TONP et des contrôles. En conclusion, la série d’études présentée dans cette thèse contribue à une meilleure compréhension du trouble de l’odorat associé à la MP et propose de potentielles pistes pour le différencier d’autres TONP, notamment par la mesure du système trigéminal. Cette thèse apporte une meilleure compréhension de l’interaction entre le système olfactif et trigéminal dans un système olfactif fonctionnel et de son altération dans les troubles olfactifs associés à la MP ou à d’autres TONP. La caractérisation de ce symptôme non-moteur pourra éventuellement aider au développement d’outils de dépistage précoce de la MP. / Olfactory dysfunction is a highly reliable non-motor symptom of Parkinson’s disease (PD) that appears several years before the possibility of a diagnosis of the disease. Hence, its study is of particular interest to help the development of early diagnosis tools and the selection of ideal candidates to participate in clinical trials that aims to test potential neuroprotective treatments. To do so, it is important to differentiate PD-related olfactory dysfunction from other non-neurodegenerative forms of olfactory dysfunctions that can be related to infections, head trauma or sinonasal disease (non-parkinsonian olfactory dysfunction: NPOD). The olfactory system is more complex than it seems and is intimately connected to the trigeminal system, a less well-known system, that allows, amongst others, the perception of sensation of freshness, warmth, and piquancy of odors. The interaction between the olfactory and trigeminal system is complex and not well understood. Trigeminal sensitivity is typically reduced in cases of an impaired olfactory system related to NPOD; however, this is not clear how both systems interact together in PD-related olfactory dysfunction. The main objective of this thesis was to principally characterize PD-related olfactory dysfunction when specifically compared to patients with NPOD. Consequently, this thesis also aimed to bring a better understanding of the interaction between the olfactory and trigeminal system in a fully functional olfactory system as well as in alterations of the olfactory system associated with PD and other NPOD. We have thus first assessed the olfactory and trigeminal sensitivity using behavioral measures (study 1). This study allowed the identification of a specific response pattern in PD patients with an altered olfactory system and an intact trigeminal system, when compared to controls, in contrast to the reduced trigeminal sensitivity observed in NPOD. We then evaluated the perception of trigeminal and olfactory dimensions of different odors (study 2). Our results suggest that the perception of trigeminal sensations is intact in patients with PD in contrast to the perception of olfactory dimensions which is reduced when compared to control participants. To better understand the interaction between the olfactory and trigeminal systems in a functioning olfactory system, we evaluated the impact of an olfactory stimulus on the capacity to lateralize a trigeminal stimulus in healthy participants (study 3). This study has demonstrated an amplification effect of the olfactory system on the trigeminal system particularly during ipsilateral co-stimulation, suggesting an interaction at the level of the olfactory mucosa. To better understand the trigeminal response in PD patients, we further investigated the peripheral and central trigeminal sensitivity in response to a pure trigeminal stimulus by means of electrophysiological measurements (study 4). We thus demonstrated a specific alteration of the trigeminal response in PD patients when specifically compared to patients with NPOD and healthy control participants. As the olfactory bulb is one of the first regions to be affected in PD, we then measured the olfactory bulb volume on MRI scans (study 5). Our results showed reduced olfactory bulb volume in PD patients as well as in NPOD, when compared to controls, but no difference between PD and NPOD patients. Interestingly, the use of deep learning techniques on MRI scans of the olfactory bulb allowed the discrimination between PD patients and NPOD patients with considerable accuracy. Finally, we investigated the functional connectivity within the chemosensory network (study 6). We identified a specific pattern of functional connectivity and chemosensory network modularity in PD patients at resting-state and while performing an olfactory or a trigeminal task, when specifically compared to patients with NPOD and controls. In conclusion, all taken together, the studies presented in this thesis contributes to a better understanding of the PD-related olfactory dysfunction and suggest potential avenues to differentiate it from NPOD, notably through the measurement of the trigeminal system. This thesis brings further knowledge regarding the interaction between the olfactory and trigeminal systems in a functional olfactory system and its alteration in cases of an impaired olfactory system related to PD or NPOD. The characterization of this non-motor symptom of the disease will eventually help the development of early diagnostic tools for PD.

The trigeminal ganglion (TG) is a complex sensory structure and multiple lines of evidence suggest that significant differences exist in anatomical, neurochemical and physiological properties between it and its equivalent structure in the somatosensory system, the dorsal root ganglion (DRG). This is likely to be a reflection, first on the unique areas of tissue innervation of the TG and second, on the unusual responses to injury which give rise to distinct pain symptoms such as toothache, migraine and temporomandibular joint disorders. In an attempt to address this disparity in knowledge, we have carried out an in-depth in vivo study investigating neurochemical populations and cell size distributions of sensory neurons within the rat TG. We have performed a detailed analysis of expression patterns for receptor components of important inflammatory mediators, NGF (TrkA), TNFα (p55) and IL-6 (gp130), along with the thermo-transducers TRPV1 and TRPM8. For each analysis we have compared our findings with those of the rat DRG. We have shown a significantly larger population of NF200+ neurons within the TG (51%) compared to the DRG (40%), and most interestingly, the majority of NF200+ neurons in the TG were within the small to medium cell size range, conferring a nociceptive phenotype. We have for the first time, determined expression of p55 and gp130 protein levels within neurochemically defined subpopulations of the TG. We show that a large proportion (33%) of TG neurons, in particular 27% of NF200+ neurons co-express p55, and thereby have the potential to respond directly to TNFα. Furthermore, we have observed gp130 protein expression to be ubiquitous within the TG, suggesting all neurons, including non-nociceptors, could respond to IL-6. In addition, we have utilised biochemical and electrophysiological techniques in vitro to measure the functional outcome of exposure of TG neurons to IL-6. We have demonstrated that IL-6 activates the JAK/STAT signalling pathway, preferentially within NF200+ neurons. Furthermore, we have shown that IL-6 sensitises the response of TG neurons to the TRPV1 agonist capsaicin, altering the gating properties and prolonging the opening time of the channel. Taken together, our findings support the emerging picture of a complex combinatorial pattern of co-expression of sensory neurochemicals, transducers and receptor components that help to define TG neuronal modality and function. We would advocate caution in making generalisations across sensory ganglia in particular in extrapolating data from the DRG to the trigeminal ganglion.