Open AccessTLR4 Antagonism Reduces Movement-Induced Nociception and ATF-3 Expression in Experimental Osteoarthritis
Author(s) -
Joana FerreiraGomes,
Miguel Martínez García,
Diana S. Nascimento,
L. Almeida,
Ernesto Quesada,
José Manuel Castro-Lopes,
David W. Pascual,
Carlos Goicoechea,
Francisco Piorino Neto
Publication year - 2021
Publication title -
journal of pain research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 49
ISSN - 1178-7090
DOI - 10.2147/jpr.s317877
Subject(s) - tlr4 , medicine , osteoarthritis , nociception , receptor , toll like receptor , pharmacology , endogeny , pathology , innate immune system , alternative medicine
Toll-like receptor 4 (TLR4) is a pattern recognition receptor involved in the detection of pathogen-associated molecular patterns (PAMPs), but also a "danger-sensing" receptor that recognizes host-derived endogenous molecules called damage-associated molecular patterns (DAMPs). The involvement of TLR4 in rheumatic diseases is becoming evident, as well as its potential role as a target for therapeutic intervention. Moreover, increasing evidence also suggests that TLR4 is implicated in chronic pain states. Thus, in this study, we evaluated whether a systemic administration of a synthetic antagonist of TLR4 (TLR4-A1) could decrease nociception and cartilage degradation in experimental osteoarthritis (OA). Furthermore, as the activation transcription factor (ATF)-3 serves as a negative regulator for TLR4-stimulated inflammatory response, we also evaluated the effect of TLR4 inhibition on ATF-3 expression in primary afferent neurons at the dorsal root ganglia (DRG).