Cutrer F M, Mitsikostas D D, Ayata G, Sanchez del Rio M
Departments of Neurology and Neurosurgery, Massachusetts General Hospital, 149 13th Street, CNY 6403, Charlestown, MA 02129, USA.
Headache. 1999 Nov-Dec;39(10):697-704. doi: 10.1046/j.1526-4610.1999.3910697.x.
We examined the effects of butalbital (30, 100, and 1000 micrograms/kg) on the number of cells expressing c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, within lamina I, IIo of the trigeminal nucleus caudalis and the nucleus of the solitary tract 2 hours after the intracisternal injection of capsaicin (0.1 mL; 15.25 mg/mL) or vehicle in urethane-anesthetized guinea pigs (N = 45). Robust c-fos-LI was observed within nuclei of cells in the trigeminal nucleus caudalis after capsaicin (329 +/- 35). Butalbital dose-dependently reduced the number of labeled cells to a maximum of 66% (1000 micrograms/kg intraperitoneally [i.p.], P < .01) in lamina I, IIo but not within area postrema, medial reticular nucleus, or the nucleus of the solitary tract. Pretreatment with bicuculline (30 micrograms/kg i.p.) blocked the effect of butalbital, thereby suggesting the importance of the GABAA receptor to activation involved in the transmission of nociceptive information. Our studies suggest the possibility that GABAA receptors might provide an important therapeutic target in migraine and related headache disorders.
我们在氨基甲酸乙酯麻醉的豚鼠(N = 45)中,于脑池内注射辣椒素(0.1 mL;15.25 mg/mL)或赋形剂2小时后,研究了布他比妥(30、100和1000微克/千克)对三叉神经尾侧核I层、IIo层以及孤束核中表达c-fos样免疫反应性(c-fos-LI,神经元激活标志物)的细胞数量的影响。注射辣椒素后,在三叉神经尾侧核的细胞核内观察到强烈的c-fos-LI(329 ± 35)。布他比妥剂量依赖性地减少了I层、IIo层中标记细胞的数量,最大减少至66%(腹腔注射1000微克/千克,P < 0.01),但在最后区、内侧网状核或孤束核中未观察到这种现象。用荷包牡丹碱(腹腔注射30微克/千克)预处理可阻断布他比妥的作用,这表明GABAA受体对伤害性信息传递中涉及的激活过程很重要。我们的研究表明,GABAA受体可能是偏头痛及相关头痛疾病的一个重要治疗靶点。