THE EFFECTS OF S-FLURBIPROFEN AND R-FLURBIPROFEN ON THE INFLAMMATION-EVOKED INTRASPINAL RELEASE OF IMMUNOREACTIVE SUBSTANCE-P - A STUDY WITH ANTIBODY MICROPROBES

Using antibody coated microprobes in anesthetized rats, we studied the intraspinal release of immunoreactive substance P during development of kaolin/carrageenan-induced inflammation in the knee joint, and the effects of S- and R-flurbiprofen on inflammation-evoked intraspinal re lease of immunoreactive substance P once inflammation was established. During the first 6 h after induction of acute inflammation, the basal release and the release of immunoreactive substance P evoked by innoc uous pressure applied to the knee showed increases (n = 4 rats). An in travenous dose of 9 mg/kg S-flurbiprofen (a potent inhibitor of cycloo xygenases that is anti-inflammatory and antinociceptive) did not signi ficantly alter the pattern of inflammation-evoked release of immunorea ctive substance P within 2 h although this dose reduced the responses of spinal cord neurons to pressure applied to the inflamed knee joint within 15 min to about 15% of the predrug value (Neugebauer et al., J. Pharmacol. Exp. Ther, 275 (1995) 618-628). The subsequent i.v. inject ion of 27 mg/kg S-flurbiprofen significantly changed the pattern of re lease of immunoreactive substance P showing a reduction of the level o f immunoreactive substance P in the dorsal horn within 1 h (n = 4 rats ). The release of immunoreactive substance P was also reduced after th e i.v. injection of 27 mg/kg R-flurbiprofen that is also antinocicepti ve but less anti-inflammatory (n = 5 rats). These data show that both S- and R-flurbiprofen reduce the inflammation-evoked intraspinal relea se of immunoreactive substance P within hours. However, the reduction of release of immunoreactive substance P does not seem to be a prerequ isite for the initial antinociceptive action of non-steroidal anti-inf lammatory drugs. It may be rather important in the long term range. (C ) 1998 Elsevier Science B.V. All rights reserved.