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...

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Bibliographic Details
Published in:International journal of rheumatic diseases Vol. 20; no. 10; pp. 1337 - 1349
Main Authors: Silva, Morgana Duarte, Cidral‐Filho, Francisco José, Winkelmann‐Duarte, Elisa Cristina, Cargnin‐Ferreira, Eduardo, Calixto, João B., Dutra, Rafael C., Santos, Adair Roberto Soares
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-10-2017
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Summary: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.
ISSN:1756-1841
1756-185X
DOI:10.1111/1756-185X.12741