Studies of mechanisms of OA-pain on a rat osteoarthritis model of the ankle joint
Notice bibliographique
Résumé
Osteoarthritis (OA), the degenerative and most common form of arthritis, is a complex disease of the whole joint and affects over 3 million Canadian adults. To this day, there is no satisfactory method of relieving osteoarthritic pain and, although chronic pain is the most reported complaint of the disease, our understanding of its driving mechanisms remains limited. Studies in this thesis were devised with the objective of contributing to understanding of the mechanism of pain in OA.Studies investigating changes of innervation of bone have been few and sparse in the literature, mostly due to the complexity and poor success of performing histological labellings on decalcified bone tissue. As a result, there has been a lack of understanding of mechanisms contributing to pain in diseases such as arthritis, osteoporosis, and low back pain. In this thesis, we developed a robust methodology for labelling nerve fibers in bone in various animal models of OA, osteoporosis, and bone fracture.In this thesis, we provide a multi-facetted time-course study of relevant changes in a mono-iodoacetate (MIA) model of OA in the rat ankle joint. We showed a correlation between pain-related behavior and pathological changes, including cartilage and bone degeneration, sprouting of sensory and sympathetic nerves in the bone and synovium, and increased density and activation of glial cells in the dorsal horn. There are many clinical and pre-clinical lines of evidence suggesting a neuropathic component to OA pain, including the occurrence of microgliosis in the spinal cord and modulation of nociceptors by sympathetic afferents. However, putative for a neuropathic pain-like component to OA is the possible contribution of primary afferent damage following joint degeneration. We have shown expression of Activating Transcription Factor 3 (ATF3), a marker of neuronal stress, principally in large-diameter cell bodies that also colocalize with parvalbumin (PV), a marker of proprioceptors. This suggests that Aβ mechanoreceptors innervating the articular joint in OA pain are mostly affected following joint degeneration, which drives interest in understanding the contribution of lamina III-V that receives input from these fibers, in the persistence of OA pain. The internalization of the receptor for substance P, the neurokinin-1 receptor (NK1-r) on lamina I projection neurons of the spinal dorsal horn has been used as a marker of nociceptive responses. Lamina I is an important centre for the modulation and forwarding to the brain of pain-related information. Therefore, changes in the properties of lamina I projection neurons may be important for pain. Previous work from our lab has shown increased expression of NK1-r on lamina I pyramidal neurons in both neuropathic pain and inflammatory arthritis models. In this thesis, we showed similar morphological changes and internalization of the receptor on NK1-r positive neurons, in a rat ankle joint model of osteoarthritis (OA) following movement of the affected joint in lamina I. This work combines many studies of important changes occurring in OA in the peripheral and central nervous systems, identifying various contributing mechanisms to chronic and irreversible pain in the disease, including a neuropathic pain-like component. Such studies have important implications in the development of more suitable therapeutic strategies by identifying potential targets
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».