Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord.

Aim: To investigate the antinociceptive, antiedematogenic and chondroprotective effects of diacerein (DIA) in a model of joint inflammation induced by complete Freund's adjuvant (CFA), as well as to investigate the involvement of metalloproteinase (MMP)-9, transient receptor potential vanilloid 1 (TRPV1) and glial cells in DIA's action mechanism.

Methods: Complete Freund's adjuvant was injected into the knee joint of male rats. We observed mechanical and cold hypersensitivity, vocalization and spontaneous pain-related behaviors, as well as edema of the knee. Tissue samples of the knee were stained with Cason`s technique and the thickness of the condilus cartilage was measured. Immunohistochemical analysis was performed on the spinal cord using anti-GFAP (glial fibrillary acidic protein), anti-MMP and anti-TRPV1 antibodies. Sections of the dorsal horns of the spinal cord were captured and an optical density was obtained.

Results: Complete Freund's adjuvant induced mechanical and thermal hypersensitivity, as well as joint edema and changes in the synovial membrane and cartilage. DIA (30 mg/kg, orally, daily) significantly inhibited mechanical (58 ± 10-87 ± 3%) and thermal (66 ± 12-87 ± 8%) hypersensitivity, vocalization (83 ± 5-41 ± 11%), spontaneous pain score, joint swelling (60 ± 6-40 ± 9%), as well as the histological changes induced by CFA. In addition, DIA inhibited astrocyte activation, and prevented the increase of MMP-9 and TRPV1 expression in the spinal cord of the animals subjected to CFA injections.

Conclusions: In short, this study shows that DIA reduces joint damage and hypersensitivity associated with inflammation induced by CFA through the inhibition of astroglial activation and decreases the expression of TRPV1 and MMP-9 in the rat spinal cord.