ISSLS Prize Winner: Repeated Disc Injury Causes Persistent Inflammation
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Notice bibliographique
Résumé
STUDY DESIGN: An in vivo rat model of disc degeneration with emphasis on characterizing acute and chronic cytokine production. OBJECTIVE: To compare the morphologic and proinflammatory response between a single and triple-stab injury in attempts to establish mechanisms of chronic disc inflammation. SUMMARY OF BACKGROUND DATA: The features that distinguish physiologic (asymptomatic) from pathologic (symptomatic) degeneration are unclear. Epidemiologic evidence suggests that cumulative damage and elevated disc cytokine levels may be linked to increased low back pain rates. Although acute injury stimulates a healing response that includes transient cytokine production, repetitive damage may be necessary to trigger the persistent inflammation suspected to underlie chronic pain. METHODS: Tail discs were exposed surgically and stabbed with a number 11 blade. During the subsequent acute healing phase, triple-stab discs were percutaneously injured with a 23-gauge needle at day 3 and then again at day 6 after the initial blade incision. Cytokine (IL-1 beta, IL-6, IL-8, and TNF-alpha) production was quantified using enzyme linked immunosorbent assay, and, in addition to MAPK signaling pathways (phosphorylated forms of ERK, JNK, and p38), was localized by immunohistochemistry. Disc architecture was evaluated using histology. RESULTS: Both single-stab and triple-stab discs degenerated with time, yet degeneration was more severe with repeated injury where nuclear proteoglycan was replaced by disorganized collagen. Four days after single-stab, there was a transient peak in IL-1 beta and IL-8 production that was localized to the wound track and associated granulation tissue. By contrast, triple-stab induced an activated annular fibroblast phenotype (p38 positive) that caused a prolonged, diffuse inflammatory response with elevated levels of TNF-alpha, IL-1 beta, and IL-8 up to 28 days after injury. Disc inflammation was accompanied by reactive changes in the adjacent vertebral marrow spaces that was initially lytic at day 4, becoming sclerotic by day 56. CONCLUSION: Our results demonstrate that repeated injury during active healing leads to persistent inflammation and enhanced disc degeneration. These data support the premise that damage accumulation and its associated inflammation may distinguish pathologic from physiologic disc degeneration. In the future, this triple-stab model may be useful to evaluate the efficacy of anti-inflammatory low back pain treatments.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 découle