Contribution of Inflammation and Bone Destruction to Pain in Arthritis: A Study in Murine Glucose-6-Phosphate Isomerase-Induced Arthritis

Autor: Matthias Ebbinghaus, Ingrid Hilger, Andreas Hess, Hans-Georg Schaible, Gisela Segond von Banchet, Sylvia Müller, Annett Eitner, Isabel Wank, Thomas Kamradt
Rok vydání: 2018
Předmět:
Zdroj: Arthritisrheumatology (Hoboken, N.J.)References. 71(12)
ISSN: 2326-5205
Popis: OBJECTIVE Arthritis is often characterized by inflammation and bone destruction. This study was undertaken to investigate the contribution of inflammation and bone destruction to pain. METHODS Inflammation, bone resorption, pain-related behaviors, and molecular markers (activating transcription factor 3 [ATF-3], p-CREB, and transient receptor potential vanilloid channel 1) in sensory neurons were measured in murine glucose-6-phosphate isomerase (G6PI)-induced arthritis, a model of rheumatoid arthritis. Depletion of Treg cells before immunization changed self-limiting arthritis into nonremitting arthritis with pronounced bone destruction. Zoledronic acid (ZA) was administered to reduce bone resorption. RESULTS Compared to nondepleted mice, Treg cell-depleted mice exhibited arthritis with more severe bone destruction and higher guarding scores (P < 0.05; n = 10 mice per group) as well as more persistent thermal hyperalgesia (P < 0.05), but displayed similar mechanical hyperalgesia at the hindpaws (n = 18-26 mice per group). These pain-related behaviors, as well as an up-regulation of the neuronal injury marker ATF-3 in sensory neurons (studied in 39 mice), appeared before the clinical score (inflammation) became positive and persisted in Treg cell-depleted and nondepleted mice. In the late stage of arthritis, Treg cell-depleted mice treated with ZA showed less bone resorption (
Databáze: OpenAIRE