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Titolo:
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/
Autore:
BURITOVA J; BESSON JM;
Indirizzi:
INSERM U161,UNITE RECH PHYSIOPHARMACOL SYST NERVEUX,2 RUE ALESIA F-75014 PARIS FRANCE EPHE F-75014 PARIS FRANCE
Titolo Testata:
British Journal of Pharmacology
fascicolo: 1, volume: 125, anno: 1998,
pagine: 87 - 101
SICI:
0007-1188(1998)125:1<87:PAOCEO>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ASPIRIN-LIKE DRUGS; IMMEDIATE-EARLY GENES; FIBER-EVOKED ACTIVITY; DORSAL HORN NEURONS; ELECTROPHYSIOLOGICAL EVIDENCE; CYCLOOXYGENASE INHIBITION; INDUCIBLE CYCLOOXYGENASE; DIFFERENTIAL INHIBITION; PROSTAGLANDIN SYNTHESIS;
Keywords:
CARRAGEENAN INFLAMMATION; C-FOS; DORSAL HORN; RACEMIC-FLURBIPROFEN; S(+)-FLURBIPROFEN; R(-)-FLURBIPROFEN; NOCICEPTION; NSAIDS; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
73
Recensione:
Indirizzi per estratti:
Citazione:
J. Buritova e J.M. Besson, "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/", British Journal of Pharmacology, 125(1), 1998, pp. 87-101

Abstract

1 We have evaluated the effects of intravenous or intraplantar racemic-, S(+)- and R(-)-flurbiprofen on both the carrageenan-evoked peripheral oedema and spinal c-Fos immunoreactivity, an indirect index of neurons involved in spinal nociceptive processes. 2 Three hours after intraplantar injection of carrageenan (6 mg in 150 mu l of saline) in awake rats, a peripheral oedema and numerous c-Fos protein-like immunoreactive (c-Fos-LI) neurons in L4-L5 segments were observed. c-Fos-LI neurons 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 oedema and spinal c-Fos expression (r=0.64, r=0.88 and r=0.84 for paw diameter, ankle diameter and number of c-Fos-LI neurons; P<0.05, P<0.001 and P<0.001 respectively). 4 Similar effects to those of intravenous racemic-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 = 0.56 and r = 0.52 respectively, P<0.05 for both). 5 For the dose of 0.3 mg 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 level (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 comparable 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-relatedly 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 respectively (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 respectively, P<0.001, P<0.01 and P<0.01) were similar to those of racemic-flurbiprofen. In contrast, intraplantar R(-)-flurbiprofen (1, 10 and 30mu g) did not have detectable effects on all studied parameters. 8 The present study provides clear evidence for potent anti-inflammatory and 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 intraplantar, R(-)flurbiprofen. These results suggest that the main site of action of racemic- and S(+)-flurbiprofen is in the periphery and indicate that the site of action of R(-)-flurbiprofen is mainly of central origin.

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Documento generato il 29/03/20 alle ore 09:23:35