Peripheral and/or central effects of racemic‐, S(+)‐ and R(−)‐flurbiprofen on inflammatory nociceptive processes: a c‐Fos protein study in the rat spinal cord

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Abstract
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. Three hours after intraplantar injection of carrageenan (6 mg in 150 μl 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. 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; PPP−1) which dose‐relatedly reduced the number of c‐Fos‐LI neurons (r=0.69, Pr=0.56 and r=0.52 respectively, P−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−1 i.v.) was necessary to obtain effects comparable to those of S(+)‐ or racemic‐flurbiprofen (0.3 mg kg−1 i.v.). Intraplantar racemic‐flurbiprofen (1, 10 and 30 μg) dose‐relatedly reduced the carrageenan‐enhanced ankle diameter (r=0.81, Pr=0.83, PPPr=0.77, r=0.60 and r=0.59 for c‐Fos‐LI neurons, paw and ankle diameters respectively, PPPBritish Journal of Pharmacology (1998) 125, 87–101; doi:10.1038/sj.bjp.0702053