中文摘要
現今已有許多證據顯示偏頭痛之發作與三叉神經血管系統有關聯。然而目前大多數的研究著重於動脈系統。至於顱內靜脈系統與偏頭痛之間，相關的研究則較缺乏。在我們之前的研究顯當中，我們發現壓迫偏頭痛發作之病人的雙側內頸靜脈(奎氏試驗)會使其頭痛程度改變(奎氏試驗反應)，同樣之測試，對於可能偏頭痛與緊縮型頭痛病患則無影響。可見偏頭痛發作中之病患對於顱內靜脈阻滯或顱內壓升高相當敏感。根據以上的結論，我們假設奎氏試驗反應是與偏頭痛之’敏感反應’有關。偏頭痛之’敏感反應’一般可區分為’周邊敏感反應’及’中樞敏感反應’兩部分。其中，前者產生時與偏頭痛患者之’搏動性痛’有相關性，當後者發生時，病患則會有’表皮異感痛’(cutaneous allodynia)的表現。此一表現可藉由’紗布搔觸法’或是’定量皮膚感覺試驗’檢測得知。’紗布搔觸法’所測得者為’搔觸性異感痛 (brushing allodynia)’屬於’動態性(dynamic)異感痛’，而’定量皮膚感覺試驗’所測得者則為’靜態性(static)異感痛’以及’溫覺異感痛’。
為了證實我們的假設，我們進行了以下一系列的研究。首先在研究一，我們利用紗布搔觸法與奎氏試驗檢測偏頭痛發作中之病患，以了解奎氏試驗反應與敏感反應之關連性。我們的結果指出奎氏試驗反應與'搏動性痛'相關，而與'搔觸性異感痛'卻無關。可見奎氏試驗反應與'周邊敏感反應'有關，與’中樞敏感反應’無關。在研究二，則是以超音波測量偏頭痛發作中病患之雙側內頸靜脈血流量與正常對照組作比較。同時也對病患進行奎氏試驗。以了解內頸靜脈血流對奎氏試驗反應之影響。我們發現偏頭痛發作中之病患其內頸靜脈血流量與’搏動性痛’ 以及’奎氏試驗反應’皆呈現正相關。因此，’內頸靜脈血流量’在’奎氏試驗反應’中，扮演重要的角色。並且’內頸靜脈血流量’與’周邊敏感反應’具相當之關聯性。
於研究三，我們希望確立偏頭痛發作中病患之’搔觸性異感痛’與病患自述之異感痛症狀之相關性。並證實由紗布搔觸法於偏頭痛發作中之病患所檢測出的搔觸性異感痛，與病患自述之異感痛症狀之關聯性良好。由此可見，’搔觸性異感痛’可作為’表皮異感痛’之良好標記。研究四則是建立大鼠之奎氏試驗動物模式，以了解奎氏試驗對於生理參數之影響。研究發現奎氏試驗或雙側總頸靜脈夾起時，皆引起大鼠腦室壓升高、血壓降低的情形，且前者之效應強於後者。
總結而言，由以上一系列研究的結果，我們已確立’奎氏試驗反應’、’周邊敏感反應’以及’內頸靜脈血流量’三者存在密切之關聯性。並證實，顱靜脈系統主要是與偏頭痛發作時的’周邊敏感反應’有關(圖一)。

關鍵詞: 偏頭痛、內頸靜脈、奎氏試驗、紗布搔觸法、搔觸性異感痛、定量皮膚感覺試驗、搏動痛、超音波、內頸靜脈血流量、大鼠奎氏試驗模式。

Abstract
Trigeminovascular system is related to migraine pathogenesis. However, the majority of previous studies focused on the arterial systems. In contrast, the studies on the intracranial venous system are insufficient. We applied the Queckenstedt’s(Q)- test in patients with acute attacks of migraine, probable migraine and tension-type headache in both sitting and lying positions. Only patients with migraine attacks reported aggravation of headache intensity. Thus, patients with acute migraine attacks appear more sensitive to cerebral venous congestion or increased intracranial pressure. We hypothesized that the mechanism of sensitization during migraine attacks is related to the headache intensity changes by Q-test (Q-test response). ‘Sensitization’ has two major components: ‘peripheral sensitization’ and ‘central sensitization’ during migraine attacks. The former is related to ‘throbbing’ character of head pain and the latter is related to development of ‘cutaneous allodynia’(CA). ‘CA’ can be tested by ‘gauze brushing test’ or ‘quantitative skin test (QST)’. The gauze brushing test can test ‘brushing allodynia’ (BA) which is one type of ‘dynamic’ allodynia. On the other hand, QST evaluates ‘static allodynia’ and ‘thermal allodynia’
To investigate our hypothesis, we designed series of studies. In study 1, we used gauze brushing test combined with the Q-test on patients with migraine attacks, to elucidate the relationship between “sensitization” in migraine and Q-test response. And we concluded that the Q-test response is correlated with throbbing quality but not BA. That is, peripheral but not central sensitization is related to the Q-test response. In study 2, we compared the Q-test and bilateral internal jugular venous flow volume (IJVFV) with the ultrasonographic technique in patients with migraine attacks .We noted that Q-test response was associated with the presence of throbbing pain and the IJVFV. Therefore, the IJVFV played a role for the Q-test response as well as peripheral sensitization
In study 3, we aimed to examine the correlation between BA and self-reported allodynic symptoms. We found that BA detected by the gauze brushing test during migraine attacks correlated well with prior allodynia symptoms, suggesting that BA can be a marker of CA. Finally, we established a rat Q-test model (study 4) to evaluate the physiological changes of the Q-test. Both the Q-test and clipping of bilateral common jugular veins resulted in increased intravetricular pressure and decreased blood pressure, but the Q-test showed a stronger effect than the clipping method.
In conclusion, our series of studies showed a good correlation between the Q-test response, peripheral sensitization, and higher IJVFV in patients with acute migraine. The contribution for venous component in migraine pathophysiology is mainly at the peripheral sensitization (Figure 1).

Key words: Migraine, internal jugular vein, Queckenstedt’s test, gauze brushing test, Quantitative skin test, brushing allodynia, throbbing pain, ultrasonographic technique, internal jugular venous flow volume, rat model

Table of Contents
English Abstract……………………………………… 1
Chinese Abstract…………………… … ………3
List of Abbreviations………… …… ………… 5
Introduction…………..………….……… …6
Materials and Methods……………… … ………… 13
Results…………………………………….…………… 22
Discussion…….………………….…….… ………… 28
Conclusion………………………….….……………… 36
Perspectives………………………….… …………… 37
References……………………….………… …… 38
Figures and Tables………….………… … ………46
Appendix………………………………… ………………72
Publications………………… …………………………77

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