S-(+)-3-isobutylgaba and its stereoisomer reduces the amount of inflammation and hyperalgesia in an acute arthritis model in the rat.
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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 swelling, pain-related behavior scores and the heat hyperalgesia induced by knee joint inflammation were compared. Infusion of either S-(+)-3-IBG or R-(-)-3-IBG through a microdialysis fiber, implanted in the dorsal horn of the spinal cord, for 1.5 h before injection of kaolin and carrageenan resulted in a 20 to 30% reduction in joint swelling compared with aCSF-treated controls, and prevented the development of heat hyperalgesia and spontaneous pain. In contrast, infusion of either stereoisomer after the development of inflammation reduced the hyperalgesia but did not reduce the amount of joint swelling compared with aCSF-treated animals. In summary, S-(+)-3-IBG and R-(-)-3-IBG are effective antihyperalgesic agents when administered both before and after joint inflammation. In addition, if administered before injection of kaolin and carrageenan into the knee joint this drug can attenuate joint inflammation. Both the antihyperalgesic and anti-inflammatory properties of this drug probably are mediated through a central neurogenic mechanism.