Effect of BIBN4096 in Neurobehavioural Changes of Nitroglycerin-induced Migraineous Rat Model

Abstract

: Background: The pathogenesis of migraine pain has not yet been adequately explained. The incidence of cognitive dysfunction and psychological symptoms, as well as their reciprocal relationships in migraine patients, is still under consideration. The study aims to characterise the neurobehavioral and molecular changes that occur during a migraine condition. Methods: For the present study, nitro-glycerine (NTG)- induced rats were treated with antimigraine drugs such as ergotamine, sumatriptan, as well as BIBN4096. The pain was measured by the hot plate method, and the motor activity was assessed using actophotometer. The neurobehavioural activities were tested by using open field, elevated plusmaze and forced swim test. Vasoactive substances such as NO and CGRP were detected in the plasma and CGRP was detected in the isolated parts of the rat’s brain. Analysis of the proinflammatory marker such as TNF-α was carried out in the serum. Histopathological changes of the animal brain were identified using Cresyl violet (Nissl body) staining. Results: A significant analgesic activity was observed with BIBN4096 (p<0.01). Significant (p<0.05) regaining of motor and neurobehavioural changes was observed in the NTG-induced migraneous animal after treatment with BIBN4096 as compared to the NTG-treated animal. But there was a non-significant difference observed in the forced swim test. Vasoactive and inflammatory markers such as NO, CGRP and TNF-α were significantly reduced on treatment with BIBN4096 (p<0.05) when compared to the model group. On Cresyl violet staining, less damage of neurons was observed with BIBN4096 treatment and a near-normal morphology of the rat’s cerebral cortex was observed. Conclusion: Thus, the present study exhibited a remarkable antimigraine effect with a CGRP antagonistic agent, BIBN4096 than the other tested drugs such as ergotamine and sumatriptan.Key words: Migraine, Nitroglycerin, CGRP, BIBN4096, Open field task, Elevated plus-maze.