The effects of S- 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 release 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 innocuous pressure applied to the knee showed increases (n=4 rats). An intravenous dose of 9 mg/kg S-flurbiprofen (a potent inhibitor of cyclooxygenases that is anti-inflammatory and antinociceptive) did not significantly alter the pattern of inflammation-evoked release of immunoreactive 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. injection of 27 mg/kg S-flurbiprofen significantly changed the pattern of release of immunoreactive substance P showing a reduction of the level of immunoreactive substance P in the dorsal horn within 1 h (n=4 rats). The release of immunoreactive substance P was also reduced after the i.v. injection of 27 mg/kg R-flurbiprofen that is also antinociceptive but less anti-inflammatory (n=5 rats). These data show that both S- and R-flurbiprofen reduce the inflammation-evoked intraspinal release of immunoreactive substance P within hours. However, the reduction of release of immunoreactive substance P does not seem to be a prerequisite for the initial antinociceptive action of non-steroidal anti-inflammatory drugs. It may be rather important in the long term range.