Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord.
OBJECTIVE
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.
Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.|Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.|Departamento de Fisioterapia, Universidade Federal do Pampa, Uruguaiana, RS, Brazil.
Morgana Duarte
MD
da Silva
Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.|Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.
Francisco José
FJ
Cidral-Filho
Departamento de Ciências Morfológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.
Elisa Cristina
EC
Winkelmann-Duarte
Laboratório de Marcadores Histológicos, Instituto Federal de Santa Catarina, Garopaba, SC, Brazil.
Eduardo
E
Cargnin-Ferreira
Centro de Inovação e Ensaios Pré-clínicos, Cachoeira do Bom Jesus, Florianópolis, SC, Brazil.|Departamento de Farmacologia, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.
João B
JB
Calixto
Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.|Laboratório de Autoimunidade e Imunofarmacologia, Universidade Federal de Santa Catarina, Araranguá, SC, Brazil.
Rafael C
RC
Dutra
Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.|Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil.
Adair Roberto Soares
ARS
Santos
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D004487:Edema / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D005620:Freund's Adjuvant; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D059226:Nociceptive Pain / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000523:psychology; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013697:Thermosensing / Q000187:drug effects; D013997:Time Factors; D014828:Vocalization, Animal / Q000187:drug effects
D000700:Analgesics; D000880:Anthraquinones; D018501:Antirheumatic Agents; D061965:Matrix Metalloproteinase Inhibitors; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C025292:diacerein; D005620:Freund's Adjuvant; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
MMP-9; TRPV1; diacerein; glial cells; joint inflammation; pain