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 II alpha (CamKIIα)-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 CamKIIα expression. In our experiments, we demonstrated that pretreatment with NS398, the selective COX-2 inhibitor attenuated the NTG-induced CamKIIα 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 CamKIIα 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.