Selective inhibition of cyclooxygenase-2 attenuates nitroglycerin-induced calmodulin-dependent protein kinase II alpha in rat trigeminal nucleus caudalis

The nitric oxide donor, nitroglycerin (NTG) can trigger a migraine attack, after a delay of several hours in migraineurs, but not in healthy people. This long delay does not favor a pure vasodilatatory action. In rats. subcutaneous administration of NTG (10 mg/kg) significantly and selectively increases the number of calmodulin-dependent protein kinase If alpha (CamKII alpha)-immunoreactive neurons in the trigeminal caudal nucleus (TNC) after 4 h. The aim of our study was to determine if any isoforms of the cyclooxygenase (COX) enzyme might have a role in the NTG-induced increase of CamKII alpha expression. In our experiments, we demonstrated that pretreatment with NS398, the selective COX-2 inhibitor attenuated the NTG-induced CamKII alpha expression in the TNC at doses of 3 and 5 mg/kg. In contrast, SC560, a selective COX-1 inhibitor failed to modulate this phenomenon in any of the dosages used (1, 5 and 10 mg/kg). These findings suggest that COX-2, but not COX-1 derived metabolites are important factors in the NTG-induced CamKII alpha expression. Thus this isoform may play a significant role in the induction of migraine. These data could help in the better understanding of the pathogenesis of headaches and the action of antimigraine drugs. (C) 2008 Elsevier Ireland Ltd. All rights reserved