Notice bibliographique
Résumé
International classification of diseases-11 (ICD-11) classifies chronic primary pain conditions like temporomandibular pain disorders and fibromyalgia syndrome under Chapter 21 ("symptoms, signs or clinical findings, not elsewhere classified"). such conditions lack well-defined etiology and diagnosis. Our understanding of chronic primary pain conditions is incomplete, and these conditions are not just limited to anomalies in sensory perception of pain but involve multiple systems. The immune system is one of those contributors to the pathophysiology of chronic primary pain. This thesis explores the role of the immune system in pain modulation. Specifically, we will focus on two chronic primary pain conditions: temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS). Chapter I would summarize the literature on the general involvement of the immune system in enhancing and resolving pain, and how immune cells and neurons interact due to neuro-immune molecular overlap. Chapter II will describe my first research project representing an important example of reverse translational research in the area of pain genetics and immunology. Here, we found an association between an inflammatory mediator, epiregulin (EREG), and chronic TMD through statistical genetics approaches. TMD, a major cause of nondental pain in the orofacial region, is characterized by craniofacial pain involving the joint, masticatory muscles, or muscle innervations of the head and neck. We found that loss of function EREG genetic variants are associated with chronic TMD and chronic pain intensity. Next, we found that the same genetic variants are analgesic during the acute stages of pain development. We then validated these associations in the large independent cohort. Finally, we were able to confirm this dichotomous role of EREG in pain through animal pain models. Chapter III deciphers the role of the immune response in another chronic musculoskeletal pain condition-fibromyalgia syndrome (FMS). FMS, a common rheumatic disease, is characterized by chronic widespread pain, fatigue, and, sleep and cognitive difficulties. Pathogenesis of this syndrome remains elusive leading to a lack of objective diagnosis and specific treatment. Although the immune system's involvement in FMS is irrefutable, the specifics are yet to be deciphered. Furthermore, numerous studies have described the presence of small fiber neuropathy in FMS patients, but the mechanism of development of this neuropathy is unknown. In chapter III, we investigate peripheral blood mononuclear cells (PBMCs) through flow cytometry and differential gene expression in a case-control manner. We found that the FMS cases have fewer circulating natural killer (NK) cells. Furthermore, these cells were activated and exhausted in FMS patients. Co-culturing these cells with HLA-/- cell line (an activation stimulus for NK cells) showed that the NK cells from FMS patients are hyperactive compare to controls. Lastly, skin biopsies from an independent cohort showed increased expression of ULBP (NK activation ligand) and recruitment of NK cells on the peripheral nerves of the patients. In summary, this thesis advances our current understanding of the immune system's involvement in chronic primary pain conditions. Firstly, it demonstrates the dichotomies role of EREG in pain development being protective against acute pain but contributing to chronic pain. Secondly, we found the contribution of NK cells to FMS through its association with peripheral nerves in FMS. Both of these findings are novel steppingstones on our understanding of the pathophysiology of chronic pain and have therapeutics implementations in the treatment of chronic primary pain conditions
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».