A型肉毒毒素治疗偏头痛的临床研究

目的:观察A型肉毒毒素治疗预防偏头痛 发作的临床疗效和不良反应。方法:选取30例偏头 痛病人,应用A型肉毒毒素进行颅周肌内注射治 疗,问卷调查记录每例偏头痛病人治疗前3mo,治 疗后mo1,2,3偏头痛发作情况,比较偏头痛发作频 率、发作持续时间、发作严重程度及使用止痛药物情 况,观察不良反应。结果:A型肉毒毒素治疗后 mo1,偏头痛发作频率、发作持续时间、发作严重程 度均较治疗前明显下降(P<0.01),止痛药物的使 用较治疗前减少(P<0.01),疗效可至少维持3mo, 且不良反应轻微、短暂。结论:A型肉毒毒素颅周肌 内注射治疗预防偏头痛发作临床疗效显著,不良反 应轻微、短暂,值得临床研究。     

逍遥滴鼻液对实验性偏头痛模型大鼠c-fos基因表达的影响

目的 :研究逍遥滴鼻液通过鼻腔给药对实验性偏头痛模型大鼠c fos基因表达的影响 ,探讨逍遥滴鼻液治疗偏头痛的作用机理。方法 :将 6 0只Wistar大鼠随机分为 6组 ,即正常对照组、模型组、生理盐水滴鼻组、太极通天口服液组、逍遥滴鼻液灌胃组及逍遥滴鼻液滴鼻组 ,根据文献方法改进 ,用硝酸甘油 9.5mg·kg-1剂量皮下注射复制偏头痛模型 ,用免疫组化SABC法观察c fos基因表达的阳性细胞数、面积及灰度 ,并进行组间比较。结果 :逍遥滴鼻液滴鼻组大鼠脑干、下丘脑中的c fos表达阳性细胞数目和面积显著低于逍遥滴鼻液灌胃组和太极通天口服液灌胃组。结论 :逍遥滴鼻液能显著抑制c fos的表达 ,其作用机理可能是干预c fos产生的某个环节 ,在作用效果上优于太极通天口服液 ,鼻腔给药优于灌胃给药     

Six novel rare non-synonymous mutations for migraine without aura identified by exome sequencing

Abstract

Migraine without aura (MWO) is the most common among migraine group, and is mainly associated with genetic, physical and chemical factors, and hormonal changes. We aimed to identify novel non-synonymous mutations predisposing to the susceptibility to MWO in a Chinese sample using exome sequencing. Four patients with MWO from a family and four non-migraine subjects unrelated with these patients were genotyped using whole-exome sequencing. Bioinformatics analysis was used to screen possible susceptibility gene mutations, which were then verified by PCR. In four patients with MWO, six novel rare non-synonymous mutations were observed, including EDA2R (G170A), UBE2NL (T266G), GBP2 (A907G), EMR1 (C264G), CLCNKB (A1225G), and ARHGAP28 (C413G). It is worth stressing that GBP2 (A907G) was absent in any control subject. Multiple genes predispose to the susceptibility to MWO. ARHGAP28-, EMR1-, and GBP2-encoded proteins may affect angiokinesis, which supports vasogenic theory for the etiological hypothesis of this disease. CLCNKB-encoded protein may affect cell membrane potential, which is consistent with the cortical spreading depression theory. UBE2NL-encoded protein may regulate cellular responses to 5-hydroxytryptamine, which is in accordance with trigeminovascular reflex theory. EDA2R and UBE2NL are located on the X chromosome, which supports that this disease may have gender differences in genetic predisposition. Replication in larger sample size would significantly strengthen these findings.     

Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs

Introduction: The introduction of the triptans (5-hydroxytryptamine (5-HT)_1B/1D receptor agonists) was a great improvement in the acute treatment of migraine. However, shortcomings of the triptans have prompted research on novel serotonergic targets for the treatment of migraine.

Areas covered: In this review the different types of antimigraine drugs acting at 5-HT receptors, their discovery and development are discussed. The first specific antimigraine drugs were the ergot alkaloids, consisting of ergotamine, dihydroergotamine and methysergide, which are agonists at 5-HT receptors, but can also bind α-adrenoceptors and dopamine receptors. In the 1990s, the triptans became available on the market. They are 5-HT_1B/1D receptor agonists, showing fewer side effects due to their receptor specificity. In the last years, compounds that bind specifically to 5-HT_1D, 5-HT_1F and 5-HT₇ receptors have been explored for their antimigraine potential. Furthermore, the serotonergic system seems to act in tight connection with the glutamatergic as well as the CGRP-ergic systems, which may open novel therapeutic avenues.

Expert opinion: Although the triptans are very effective in treating migraine attacks, their shortcomings have stimulated the search for novel drugs. Currently, the focus is on 5-HT_1F receptor agonists, which seem devoid of vascular side effects. Moreover, novel compounds that affect multiple transmitter and/or neuropeptide systems that are involved in migraine could be of therapeutic relevance.     

偏头痛伴发脑微出血的相关危险因素分析

目的分析偏头痛患者伴发脑微出血(CMBs)的临床特点及影响因素。方法连续收集178例临床确诊的偏头痛患者,根据头颅MRI有无CMBs表现分为两组,收集患者一般资料,头痛特点并进行比较。结果 (1)178例偏头痛患者中CMBs患者56例,偏头痛合并CMBs发生率为31.5%,其中单发病灶17例(30.4%),多发病灶39例(69.6%),单纯脑叶病灶31例(55.4%);(2)与无CMBs的偏头痛患者比较,合并CMBs的偏头痛患者更容易合并高血压(P=0.028),头痛病程长(P=0.002)、头痛发作频率高(P=0.001)且容易伴发先兆(P=0.036);(3)多因素Logistic回归分析显示,在校正年龄、性别及其他危险因素后,头痛病程(OR=1.166,95%CI:1.044~1.303,P=0.007)、头痛发作频率(OR=1.353,95%CI:1.116~1.640,P=0.002)和先兆偏头痛(OR=10.080,95%CI:1.630~62.329,P=0.013)与偏头痛发生CMBs相关。结论偏头痛病程长、发作频率高及伴有先兆是偏头痛发生CMBs的危险因素。