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　 Sep;123 ( Pt 9):1830-7.

論文抄録

An experimental model of headache offers unique possibilities to study the mechanisms responsible for head pain. Using the glyceryl trinitrate [GTN; nitri oxide (NO) donor] model of experimental headache, we studied the intensity, quality and time profile of headache after infusion of GTN in 16 patients with chronic tension-type headache and in 16 healthy controls. Subjects were randomized to receive intravenous infusion of GTN (0.5 microg/kg per minute for 20 min) or placebo on two headache-free days separated by at least 1 week. Headache intensity was measured on a 10-point verbal rating scale during 2 h of observation and for the next 10 h after discharge from hospital. The primary endpoints were the difference between the area under the curve (AUC-intensities x duration) for headache recorded on the day of GTN treatment and on the day of placebo treatment in patients, and in patients and controls on the days of GTN treatment. In patients, the AUC on a GTN day [2221 (1572-3704); median with quartiles in parentheses], was significantly greater than on a placebo day [730 (60-1678), P: = 0. 008]. On the GTN day, the AUC in patients [2221 (1572-3704)] was significantly higher than in controls [43 (0-972), P: = 0.0001]. In patients, peak pain intensity occurred 8 h after infusion of GTN, whereas in controls it occurred 20 min after the start of infusion. The present study demonstrates that an NO-induced biphasic response with an immediate and a delayed headache is common to chronic tension-type headache and migraine. Furthermore, the NO-induced delayed headache has the characteristics of the primary headache disorder. This suggests that NO contributes to the mechanisms of several types of primary headaches and that NO-related central sensitization may be an important common denominator in the pain mechanisms of primary headaches.

文献 PubMed － ID

PMID:10960046

エビデンスレベル

Ib

文献タイトル ( 日本語 )

慢性緊張型頭痛患者における 一酸化窒素誘発性頭痛

目的

慢性緊張型頭痛患者と健康対照者で， ND donor である glyceryl trinitrate(GTN) 点滴静注後に誘発される頭痛に違いがあるか否かを検証すること．

研究デザイン

無作為二重盲検プラセボ対照交差試験（ Randomized, double-blind, placebo-controlled crossover study ）

研究施設

Glostrup Hospital , University of Copenhagen , Denmark

研究期間

N/A

対象患者

外来通院中の 16 人の CTTH 患者と 16 人の健康成人

介入

N/A

主要評価項目とそれに用いた統計学的手法

GTN 点滴静注後 2 時間とその後 10 時間の頭痛強度を 10 point 式 visual analogue scale で記録した．主要評価項目は，頭痛カーブ曲線で示された頭痛面積 (AUC) であり， GTN とプラセボ投与時の AUC を比較おし，更に，健常者結果とも比較した．

結果

患者の AUC は， GTN 投与時の方がプラセボ投与時に比べ有意に高かった（ AUC 中央値： 2221 (1572-3704)vs. 730 (60-1678), P=0.008 ） . また，患者の GTN 投与時の AUC は健康成人の値に比し有意に高かった（ AUC 中央値： 2221 (1572-3704)vs. 43 (0-972), P=0.0001 ）．患者においては，頭痛強度は GTN 投与 8 時間後にピークに達したが，健常者では投与開始後 20 分後にピークに到達した．

結論

NO 誘発性即時および遅発性頭痛の２相性の応答は，片頭痛および慢性緊張型頭痛に共通して認められる現象であり， NO 誘発性遅発性頭痛は一次性頭痛の特徴であると言える．このことから，種々の一次性頭痛の発症機序に NO が関与していると推測され， NO に関連する中枢性感作が一次性頭痛の痛み発現機序に重要な役割を果たしていると推測される ．

備考

Publication Types:
* Clinical Trial

MeSH Terms:
* Adult
* Chronic Disease
* Cross-Over Studies
* Double-Blind Method
* Female
* Hemodynamic Processes/drug effects
* Hemodynamic Processes/physiology
* Humans
* Male
* Middle Aged
* Migraine/chemically induced
* Migraine/physiopathology*
* Nitric Oxide/metabolism*
* Nitric Oxide Donors/administration & dosage
* Nitric Oxide Donors/adverse effects*
* Nitroglycerin/administration & dosage
* Nitroglycerin/adverse effects
* Placebos/administration & dosage
* Placebos/adverse effects
* Reaction Time/drug effects
* Reaction Time/physiology
* Research Support, Non-U.S. Gov't
* Tension Headache/chemically induced*
* Tension Headache/physiopathology*
* Time Factors

Substances:
* Nitric Oxide Donors
* Placebos
* Nitric Oxide
* Nitroglycerin

作成者

飯塚高浩