Investigating behavioral effects of nitroglycerin induced headache in rats

Migraine is a common disabilitating disease especially in women. Human studies are limited, so animal migraine models are important. Animal models have been used to investigate migraine pathophysiology and treatment options. GTN triggers migraine attack in migraine patients and animal headache models. There are acute migraine models in the literature. In this study it is the first time NCNL model is used to mimic chronic migraine and GTN was administered for acute attack. The effect of sumatriptane, CGRP receptor antagonist was investigated. Extravasation of dura mater was investigated. Mechanical allodynia and thermal hyperalgesia was tested by VF/ EVF and acetone. Also elevated plus maze was used to evaluate anxiety. c-fos immunoreactivity in brain and brain stem pain related structures was studied. This is the first time extravasation in dura mater was shown in freely moving rats which confirms the validity of the model as migraine model. NCNL ligation and GTN administration model demonstrated mechanical allodynia and thermal hyperalgesia confirming central and peripheral sensitization. Concordant with this data, immunhistochemistry disclosed significantly increased c-fos immunoreactivity in ipsilateral brainstem TNC compared to contralateral. c-fos was positive in cortical structures constituting pain matrix. Anxiety accompanying pain was confirmed by elevated plus maze test. As a result, equivalent migraine models to human migraine is still a debate. Studies are going on considering the advantages and disadvanges of animal models on CGRP receptor antagonists. In this study chronic pain model by NCN ligation was performed and acute pain by GTN was trigerred. This model was confirmed similar to human chronic migraine and seems convenient for further drug studies.