PERIPHERAL AND OR CENTRAL EFFECTS OF RACEMIC-FLURBIPROFEN, S(+)-FLURBIPROFEN AND R(-)-FLURBIPROFEN ON INFLAMMATORY NOCICEPTIVE PROCESSES - A C-FOS PROTEIN STUDY IN THE RAT SPINAL-CORD/

1 We have evaluated the effects of intravenous or intraplantar racemic -, S(+)- and R(-)-flurbiprofen on both the carrageenan-evoked peripher al oedema and spinal c-Fos immunoreactivity, an indirect index of neur ons involved in spinal nociceptive processes. 2 Three hours after intr aplantar injection of carrageenan (6 mg in 150 mu l of saline) in awak e rats, a peripheral oedema and numerous c-Fos protein-like immunoreac tive (c-Fos-LI) neurons in L4-L5 segments were observed. c-Fos-LI neur ons were essentially located in the superficial (I-II) and deep (V-VI) laminae of the dorsal horn. 3 Intravenous racemic-flurbiprofen (0.3, 3 and 9 mg kg(-1)) dose-relatedly reduced the carrageenan-evoked oedem a and spinal c-Fos expression (r=0.64, r=0.88 and r=0.84 for paw diame ter, ankle diameter and number of c-Fos-LI neurons; P<0.05, P<0.001 an d P<0.001 respectively). 4 Similar effects to those of intravenous rac emic-flurbiprofen were obtained with intravenous S(+)flurbiprofen (0.3 , 3 and 9 mg kg(-1)) which dose-relatedly reduced the number of c-Fos- LI neurons (r = 0.69, P< 0.01) and diameters of paw and ankle (r = 0.5 6 and r = 0.52 respectively, P<0.05 for both). 5 For the dose of 0.3 m g kg(-1) i.v., R(-)-flurbiprofen did not modify the number of c-Fos-LI neurons and produced a weak reduction of oedema at only the ankle lev el (23+/-12% reduction, P<0.05). However, a ten times higher dose of R (-)-flurbiprofen (3 mg kg(-1) i.v.) was necessary to obtain effects co mparable to those of S(+)- or racemic-flurbiprofen (0.3 mg kg(-1) i.v. ). 6 Intraplantar racemic-flurbiprofen (1, 10 and 30 mu g) dose-relate dly reduced the carrageenan-enhanced ankle diameter (r=0.81, P<0.001) and the number of c-Fos-LI neurons in L4-L5 segments (r=0.83, P<0.001) , with a 60+/-3% reduction of the number of c-Fos-LI neurons (P<0.001) , and 30+/-3 and 67+/-7% reduction of paw and ankle diameter respectiv ely (P<0.001 for both) for the dose of 30 mu g. 7 For intraplantar S(S )-flurbiprofen (1, 10 and 30 mu g) the dose-related effects (r=0.77, r =0.60 and r=0.59 for c-Fos-LI neurons, paw and ankle diameters respect ively, P<0.001, P<0.01 and P<0.01) were similar to those of racemic-fl urbiprofen. In contrast, intraplantar R(-)-flurbiprofen (1, 10 and 30 mu g) did not have detectable effects on all studied parameters. 8 The present study provides clear evidence for potent anti-inflammatory an d antinociceptive effects of both intravenous or intraplantar racemic- and S(S)-flurbiprofen. These results further demonstrate marked anti- inflammatory and antinociceptive effects of intravenous, but not intra plantar, R(-)flurbiprofen. These results suggest that the main site of action of racemic- and S(+)-flurbiprofen is in the periphery and indi cate that the site of action of R(-)-flurbiprofen is mainly of central origin.