Effects of parecoxib on plasma protein extravasation and c-fos expression in the rat.
OBJECTIVE
We aimed to investigate the effects of the cyclooxygenases-2 (COX-2) inhibitor parecoxib on meningeal plasma protein extravasation (PPE) and on c-fos expression in the nucleus trigeminalis caudalis in an animal model of trigeminovascular activation. Background.-Recent reports about the efficacy of COX-2 inhibitors in migraine treatment suggest the involvement of COX-2 in migraine pathophysiology. So far, studies on the role of COX-2 in animal models of migraine are lacking.


METHODS
Unilateral electrical stimulation of the trigeminal ganglion was performed in anesthetized male Sprague Dawley rats. We assessed PPE in the ipsilateral dura mater and expression of c-fos within the ipsilateral trigeminal nucleus caudalis (TNC) under control conditions and after pretreatment with parecoxib.


RESULTS
Parecoxib significantly attenuated PPE in the rat dura mater. The PPE ratio under control conditions (1.73 +/- 0.19 (mean +/- SD)) was reduced by 58.9 +/- 30% after pretreatment with 10 mg/kg parecoxib and by 78.1 +/- 23% after pretreatment with 50 mg/kg. c-fos experiments: Compared with vehicle, all doses of parecoxib (1 mg/kg, 10 mg/kg, 50 mg/kg) significantly reduced the number of c-fos positive cells in the ipsilateral TNC (P < .05). The number of c-fos positive cells in the ipsilateral TNC was 50 +/- 2.7 (mean +/- SEM) under control conditions and 9.1 +/- 0.6 after pretreatment with 50 mg/kg parecoxib.


CONCLUSIONS
Our study results suggest that COX-2 is involved in neurogenic inflammation of the rat dura mater. Moreover, the study points to a role of COX-2 inhibitors in trigeminal nociception at the second-order level.
Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Sigrid
S
Schuh-Hofer
Mandana
M
Tayefeh
Uwe
U
Reuter
Ulrich
U
Dirnagl
Guy
G
Arnold
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001798:Blood Proteins; D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; D016760:Proto-Oncogene Proteins c-fos; C409945:parecoxib