Anti-nociceptive effect of thalidomide on zymosan-induced experimental articular incapacitation.
The anti-nociceptive effect of thalidomide on zymosan-induced articular knee joint incapacitation in rats was investigated. Thalidomide (5-45 mg/kg), given 30 min before but not 2 h after the intra-articular injection of zymosan, inhibited the nociceptive response in a dose-dependent manner. Furthermore, thalidomide pretreatment significantly reduced the concentration of tumor necrosis factor-alpha (TNF-alpha, -68.4%) in the exudate of zymosan-injected joints, but not those of interleukin-1beta, interleukin-6, CINC-1 or interleukin-10. The expression of TNF-alpha, determined by immunohistochemical staining, in synovial tissues obtained from articular joints injected with zymosan was also inhibited by thalidomide pretreatment. The anti-nociceptive effect of thalidomide was not reversed by the co-administration of an opioid receptor antagonist, naloxone, suggesting that endogenous opioids do not mediate the anti-nociceptive effect of thalidomide in this model. In conclusion, the anti-nociceptive activity of thalidomide in zymosan-induced articular incapacitation is associated with the inhibition of TNF-alpha by resident synovial cells.
Vale
Mariana L
ML
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará. R. Cel. Nunes de Melo 1127, Rodolfo Teófilo, 60.430-270 Fortaleza CE, Brazil. marianavale@yahoo.com
Cunha
Fernando Q
FQ
Brito
Gerly A C
GA
Benevides
Verônica M
VM
Ferreira
Sérgio H
SH
Poole
Stephen
S
Ribeiro
Ronaldo A
RA
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018771:Arthralgia / Q000517:prevention & control*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007719:Knee Joint / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan
D000700:Analgesics; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D009292:Narcotic Antagonists; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D013792:Thalidomide; D015054:Zymosan