Conclusion
The TLR4 antagonist administration possibly interrupts the TLR4 signalling cascade, thus decreasing the neurotoxic environment at the joint, which leads to a reduction in ATF-3 expression and in nociception associated with experimental OA.
Methods
OA was induced in adult male Wistar rats through an intra-articular injection of 2 mg of sodium mono-iodoacetate (MIA) into the left knee. From days 14 to 28 after OA induction, animals received an intraperitoneal injection of either TLR4-A1 (10 mg/kg) or vehicle. Movement- and loading-induced nociception was evaluated in all animals, by the Knee-Bend and CatWalk tests, before and at several time-points after TLR4-A1/vehicle administration. Immunofluorescence for TLR4 and ATF-3 was performed in L3-L5 DRG. Knee joints were processed for histopathological evaluation.
Results
Administration of TLR4-A1 markedly reduced movement-induced nociception in OA animals, particularly in the Knee-Bend test. Moreover, the increase of ATF-3 expression observed in DRG of OA animals was significantly reduced by TLR4-A1. However, no effect was observed in cartilage loss nor in the neuronal cytoplasmic expression of TLR4 upon antagonist administration.