The Effect of Calcium Channel Blockers on Experimental Arthritis Induced by Complete Ferund's Adjuvant Injection in Rat Knee

Rheumatoid arthritis is a chronic inflammatory disorder of connective tissue that has affected 1% of human population. The role of calcium antagonists in acute inflammation has shown by previous studies. Therefore the aim of the present study was to investigate the effect of verapamil and nifedipine (two calcium antagonists) on experimental arthritis induced by complete Ferund’s adjuvant (CFA) in rat knee. This experimental study was carried out in 8 groups of adult male rats. In group 1 and 2 (CFA and control group), 0.2 ml of CFA or saline solution were injected respectively. Groups 3and 4 received 100 and 800µg/kg nifedipine and groups 5 and 6 received the same doses of verapamil orally 7 days after injection of CFA till the end of study. Group 7 (solvent group) received dimethyl sulfoxide (DMSO) as same as groups 5 and 6 and group 8 received 15mg/kg ibuprofen daily from day 7th orally with gastro-intestinal tube. The changes caused by chronic inflammation were evaluated by measurement the knee diameter and Evans blue (E.B) content through 28 through days of CFA injection. The finding of this study showed that on day 7th after CFA injection the knee diameter (13.1±0.2mm) increased significantly compared to the day zero (9.99±0.08 mm). The increasing of diameter was significant till the end of study (day 28) (p<0.001). DMSO failed to reduce the increased diameter induced by CFA but the high dose of nifedipine on day 14, 21 and 28 and its low dose only on day 28 reduced the increased diameter significantly (p<0.01). The low dose of verapamil on days 14 and 28 and its high dose only on day 28 have had an inhibitory effect. Ibuprofen inhibited the increased diameter during all 28 days of study significantly (p<0.01). The E.B content before the injection of CFA was 2.97±0.14 µg/100mg tissue that increased significantly after injection of CFA. Whereas 7 days after CFA injection, E.B content was 12.37±0.7µg/100mg tissue (p<0.001). Either low or high dose of calcium channel blockers had significant inhibitory effect on E.B content on days 14, 21 and 28 p<0.001. The inhibitory effect of calcium channel blockers on E.B content was comparable to ibuprofen effect on the day 28. The findings of this study showed that nifedipine and verapamil can inhibit the experimental arthritis induced by CFA injection into the rat knee, by reducing the knee diameter and decrease the E.B content (albumin leakage).