All 22 preclinical investigations suggested that based on the different behavioral tests, biochemical parameters, histological and immunohistochemistry reports revealed that Nitroglycerine has the capacity to damage the neuronal cells, over expression of NLRP3, Brain derived neurotrophic factor (BDNF), Nerve growth factor (NGF), RIPK1 activation, neuroinflammation, cognitive impairment, NFkB, TXNIP, ADAR3, p-ERK, c-Fos, HMGB1 and Neurotrophin-3 (NT3) may be responsible for the migraine attack. Here, HMGB1 is linked to Cognitive impairment.