DOES PGE2 MEDIATEINDOMETHACIN AND THEOPHYLLINE EFFECTS ON JOINT DIAMETER AND VASCULAR RESPONSE TO SAPHENOUS NERVE STIMULATION IN CHRONICALLY INFLAMED RAT KNEE JOINT

Introduction: In this study the role of PGE2 as an important inflammatory mediator in indomethacin and theophylline effects on joint diameter and vascular response to saphenous nerve stimulation in chronically inflamed rat knee joint was investigated. Methods: Inflammation was induced by intraarticular injection of 0.2 ml Freunds Complete Adjuvant (FCA). 3, 7, 14 and 21 days post injection, knee joint diameter, blood flow changes induced by saphenous nerve stimulation and PGE2 content of the joint were assessed using micrometer, laser Doppler flowmeter and an enzyme immunoassay kit, respectively. These variables were also determined in another three groups, control, inflamed receiving indomethacin or inflamed receiving theophylline. also Results: After induction of inflammation in the knee joint, constrictory response of the joint vessels to saphenous nerve stimulation was reduced but joint diameter was enhanced significantly. Theophylline administration decreased both vascular response of the knee joint to nerve stimulation and joint diameter. Daily administration of indomethacin had no effect on joint edema but increased the constrictory response of the joint vessels to nerve stimulation. Furthermore PGE2 content increased in inflamed knee joint in comparison with control (un-inflamed) during two weeks but in rats receiving indomethacin it was reduced significantly on days 3, 14. Also in inflammation induced rats treated by theophylline, PGE2 content was significantly decreased only on day 14. Conclusion: In chronic inflammation, PGE2 as an inflammatory mediator play an important role in edema and modulation of constrictory response of the joint vessels to nerve stimulation. Furthermore antiedema effect of theophylline also may be mediated by PGE2 through reduction of vascular permeability.