Get access

Cox-2 Inhibitor Attenuates NO-Induced nNOS in Rat Caudal Trigeminal Nucleus


  • Hedvig Varga MSc,

  • Arpad Pardutz MD, PhD,

  • Eniko Vamos MSc,

  • Imola Plangar,

  • Eszter Egyud,

  • Janos Tajti MD, PhD,

  • Ferenc Bari PhD, DSc,

  • Laszlo Vecsei MD, PhD, DSc

  • From the Neurology Research Group of the Hungarian Academy of Sciences and the University of Szeged, Szeged, Hungary (Drs. Varga, Tajti, and Vecsei); Department of Neurology, University of Szeged, Szeged, Hungary (Drs. Pardutz, Vamos, Plangar, Egyud, Tajti, and Vecsei); and Department of Physiology, University of Szeged, Szeged, Hungary (Dr. Bari).

Address all corresponence to Dr. Arpad Pardutz, Department of Neurology, University of Szeged, Semmelweis u. 6. H-6725 Szeged, Hungary.


Objective.—The aim of the present study was to determine which isoform of the cyclooxygenase (COX) enzyme plays a role in the neuronal nitric oxide synthase (nNOS) activation caused by nitroglycerin (NTG), in the most caudal part of the trigeminal caudal nucleus (TNC) of the rat.

Background.—Nitric oxide donor, NTG, can trigger migraine attack in migraineurs, but not in healthy persons. In rats, subcutaneous administration of NTG (10 mg/kg) increases significantly the number of nNOS-immunoreactive neurons in the TNC after 4 hours, which could be attenuated by acetyl-salicylate (Aspirin), a nonselective COX-inhibitor.

Methods.—SPRD rats were divided into 3 groups: (1) control group (no drug administration), (2) NS398 (selective COX-2 inhibitor) administration (1, 3, or 5 mg/kg), and (3) SC560 (selective COX-1 inhibitor) administration (1, 5, or 10 mg/kg). Thirty minutes after drug administration, the animals received NTG (10 mg/kg) or placebo injection. Four hours later the animals were transcardially perfused and the cervical part of the TNC was removed for immunohistochemistry.

Results.—The selective COX-2 inhibitor NS398 in contrast to the selective COX-1 inhibitor SC560 attenuates the NTG-induced nNOS expression dose-dependently.

Conclusion.—These findings suggest that metabolites deriving from COX-2 (but not COX-1) may be the most important factors in the NTG-induced nNOS expression. These data could help to better understand the pathogenesis of headaches and the action of antimigraine drugs.