S-(-3-LSOBUTYLGABA AND ITS STEREOISOMER REDUCES THE AMOUNT OF INFLAMMATION AND HYPERALGESIA IN AN ACUTE ARTHRITIS MODEL IN THE RAT())

The present study investigated whether spinal administration of S-(+)- 3-isobutylgaba (S-(+)3-IBG) or its stereoisomer, R-(-)-3-isobutylgaba (R-(-)3-IBG), are effective in reducing the hyperalgesia and swelling observed after injection of kaolin and carrageenan into the knee joint of the rat. The effects of pretreatment and post-treatment of S-(+)-3 -IBG, R-(-)-3-IBG and artificial cerebrospinal fluid (aCSF) on the swe lling, pain-related behavior scores and the heat hyperalgesia induced by knee joint inflammation were compared. Infusion of either S-(+)-3-I BG or R-(-)-3-IBG through a microdialysis fiber, implanted in the dors al horn of the spinal cord, for 1.5 h before injection of kaolin and c arrageenan resulted in a 20 to 30% reduction in joint swelling compare d with aCSF-treated controls, and prevented the development of heat hy peralgesia and spontaneous pain. In contrast, infusion of either stere oisomer after the development of inflammation reduced the hyperalgesia but did not reduce the amount of joint swelling compared with aCSF-tr eated animals. In summary, S-(+)-3-IBG and R-(-)-3-IBG are effective a ntihyperalgesic agents when administered both before and after joint i nflammation. In addition, if administered before injection of kaolin a nd carrageenan into the knee joint this drug can attenuate joint infla mmation. Both the antihyperalgesic and anti-inflammatory properties of this drug probably are mediated through a central neurogenic mechanis m.