The Actions of  Sodium Valproate in Headache model Evoked by Substance-P in rats.

J Korean Neurol Assoc > Volume 16(1); 1998 > Article

Journal of the Korean Neurological Association 1998;16(1): 1-7.

Substance-P에 의해 유발된 흰쥐 두통 모델에 있어서Sodium Valproate의 작용에 관한 연구

한진규, 박민규, 박건우, 이대희

고려대학교 의과대학 신경과학 교실

The Actions of Sodium Valproate in Headache model Evoked by Substance-P in rats.

Jin Kyu Han, M.D., Min Kyu Park, M.D., Kun Woo Park, M.D., Dae Hie Lee, M.D.

Department of Neurology, Korea University, College of Medicine

Abstract

Background and Purpose : Valproic acid (2-propylpentanoic acid) which enhances GABA synthesis and blocks it’s degradation has been useful treatment of migraine and may activate GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. But the mechanism and action of sodium valproate in headache is not clear. To investigate the mechanism of valproic acid action in headache model, we compared the change of dural plasma protein extravasation in both substance-P neurogenic inflammation rats with valproic acid pretreatment and without valproic acid pretreatment. Method: Sprague-Dawely rats were pretreated with valproate 30 minutes prior to substance-P administration in order to test the effects of sodium valproate on dural plasma protein extravasation by detecting the amount of extravasated Evans blue in the dura matter. To examine the abilities of either bicuculine (GABAA antagonist) and phaclofen (GABAB antagonist) to reverse the effect of valproate, they were administered 5 min before valproate administration. After then we also test the effect of muscimol (GABAA agonist) and bicuculine (GABAA antagonist) in substance-P induced neurogenic inflammation rats.
Results: Intraperitoneal injection of sodium valproate and muscimol reduced dural plasma protein extravasation after intravenous substance-P administration. The GABAA antagonist bicuculine completely reversed the effect of valproate and muscimol on plasma extravasation following substance-P administration, whereas the GABAB receptor antagonist, phaclofen, did not.
Conclusion: We concluded that the attenuation of dural plasma protein extravasation by valproate and muscimol is mediated by via GABAA receptors within the meninges. Agonists and modulators at the GABAA receptor may become useful for the development of selective therapeutic agents for migraine headache. Key words : Valproic acid, GABA, Neurogenic inflammation.