難治的偏頭痛讓科學家頭痛

The hunt is intensifying for new treatments for migraines, the common and debilitating headaches that have confounded scientists for decades.
人類正在加緊尋求治療偏頭痛的方法，這種讓人身體虛弱的常見頭痛病已經困擾了科學家數十年。

Of greatest focus for researchers is a brain chemical known as CGRP, which appears to play a role in the transmission of pain, but not in other brain functions, such as cognition or mood. Researchers are trying a variety of experimental drugs to stop CGRP from working by blocking its receptors in the brain. Others are working on artificial antibodies that could soak up the chemical in the bloodstream or brain before it can trigger migraines.
研究人員關注最多的是一種名爲降鈣素基因相關口（CGRP）的大腦化學物質，這種物質似乎與痛感傳遞有關，但是在認知或情緒等大腦的其它功能方面並沒有造成影響。研究人員嘗試使用各種實驗藥物，通過屏蔽大腦裏感應CGRP的部分來阻止CGRP發生作用。還有一些人正致力於人工抗體的研製，使其在CGRP引發偏頭痛之前將血液或大腦中的這種化學物質吸收。

Experts say the need for new medicines to treat migraine pain once it begins is great because current drugs only provide some benefit for 50% to 60% of sufferers and can't be used in people with heart disease or who have had a stroke. Also, they aren't a cure, and in many cases, the headaches tend to come back within 24 hours.
專家說，治療偏頭痛的新藥一旦面世就會有巨大需求，因爲目前的藥物只對大約50%-60%的患者有一定療效，並且心臟病患者和有中風病史的人都不能服用。而且這些藥物並不能治本，在很多病例中，患者在24小時內又會出現頭痛。

There also is a separate category of preventive drugs, which tend to be used by a small proportion of people who suffer from more frequent or debilitating migraines.
還有一種單獨類型的預防性藥物，使用者一般是一小部分偏頭痛發生頻率較高或發作起來更難受的人。

'People need migraine drugs that have a rapid onset of action, that take the pain away and keep it away,' says Richard Lipton, director of the Montefiore Headache Center in New York.
“人們需要立竿見影的偏頭痛藥，能夠止痛並讓它不再復發，”紐約蒙特菲奧裏頭痛研究中心（Montefiore Headache Center）的主任理查德•利普頓（Richard Lipton）說。

 Headache disorders are among the most common medical conditions world-wide. More than 1 in 10 adults globally are affected by migraines, which can be incapacitating, according to the World Health Organization. International studies have found that 50% to 75% of adults have reported a headache in the past year, with up to 4% of the global population reporting having a headache in half or more of the days each month, WHO says.
頭痛症是全世界最常見的醫學病症之一。根據世界衛生組織（World Health Organization）的數據，在全球範圍內，每10名成年人中就有1人以上身受可能讓人無法正常行動的偏頭痛之苦。世衛組織說，國際研究發現，在過去的一年裏，有50%-75%的成年人聲稱發生過頭痛。全球人口中有4%的人每月有一半或者一半以上的日子裏會發生頭痛。

There isn't such a thing as a 'regular' headache, but rather more than 300 types, says David Dodick, a professor of neurology at the Mayo Clinic's branch in Phoenix and chairman of the American Migraine Foundation. People having migraines usually experience intense pain, sensitivity to light, dizziness and sometimes nausea and visual and sensory symptoms called auras. Two other major types of headaches are caused by tension or medication overuse.
美國梅約診所（Mayo Clinic）鳳凰城分所神經學教授、美國偏頭痛基金會（American Migraine Foundation）主席大衛•多迪克（David Dodick）說，頭痛沒有一種“常規”病症，而是有300多種類型他也是。患偏頭痛的人通常會感受到劇痛、對光線敏感、頭暈，有時會感到噁心，還會有一些被稱爲先兆的視覺和知覺症狀。另外兩大類頭痛的成因是緊張或藥物使用過度。

Nonsteroidal anti-inflammatory painkillers such as ibuprofen work for some migraine sufferers. But the class of migraine medicines that hit the market in the 1990s called triptans remain the best or only treatment option for many patients. Nevertheless, about half of sufferers don't respond to them or can't take them because of other health reasons.
像布洛芬這樣的非類固醇抗炎鎮痛藥對某些偏頭痛患者有效。但是上世紀90年代面市的曲坦類偏頭痛藥對很多患者來說仍然是最好或唯一的藥物選擇。然而，大約一半的患者要麼服用這類藥後沒有效果，要麼由於其他健康原因不能服用此類藥物。

CGRP, which stands for calcitonin gene-related peptide neurotransmitter, has long been thought to play a role in migraines, but for much of that time for the wrong reason. Part of the confusion was because of a misunderstanding of migraines themselves.
CGRP是降鈣素基因相關口神經遞質的縮寫，長久以來它被認爲在偏頭痛中發揮了作用，不過很長一段時間裏這種看法的依據都是錯誤的。出現混亂的原因是對偏頭痛本身產生了誤解。

Why they occur still isn't clear, but specialists say they have recently begun to understand the migraine as a brain disorder and not a vascular disorder. Until about 12 years ago, they were believed to stem from constriction of blood vessels in the brain. The dilation of the vessels to compensate then led to the throbbing pain, so the thinking went.
偏頭痛發生的原因尚不清楚，但是專家們說他們最近開始把偏頭痛當作一種大腦病症而非血管病症。直到大約12年前，偏頭痛都被認爲是由於大腦血管收縮引起的。血管的補償性擴張就導致了搏動痛，當時的人們就是這麼想的。

Now, it appears more likely that migraines 'hijack' the brain's normal pain circuitry, says Dr. Dodick. The brain's normal pain-sensory system, in which nerve endings send messages to the brain about a threat, goes awry in migraines.
多迪克說，現在看來，更有可能是偏頭痛“攔截”了大腦的正常疼痛迴路。在大腦正常的疼痛感知系統裏，神經末梢會將威脅信息發送給大腦，偏頭痛發生時這個系統就會出錯。

Experts disagree about how a migraine is triggered, but the trigeminal nerve - an important pathway that carries sensory information about the face - and its connections to numerous other nerves and the brain appear to be responsible for transmitting the pain.
偏頭痛是如何引發的？專家們對此意見不一，但是三叉神經（傳遞面部周圍感官信息的重要途徑）以及它與其它各種神經和大腦的連接神經似乎是傳遞疼痛的介質。Researchers also have isolated certain genes that might be linked to a predisposition for migraines, Dr. Dodick says.
多迪克醫生說，研究人員已經把某些與易患偏頭痛體質相關的基因分離出來。

Triptans, which promote blood-vessel constriction and inflammation, block the release of CGRP in the trigeminal nerve. While CGRP does aid the blood-vessel dilation process, its role activating the nerves in the brain appears to be the key when it comes to migraine pain.
引起血管收縮和發炎的曲坦類藥物可以阻止三叉神經中CGRP的釋放。雖然CGRP的確促進了血管的擴張進程，但在偏頭痛問題上，它對激活大腦神經所起的作用似乎纔是最關鍵的。

In the mid-1980s, Peter Goadsby, a neurologist and headache specialist at the University of California San Francisco, and his colleagues found that CGRP is released in migraines and that triptans decreased CGRP action.
20世紀80年代中期，加州大學舊金山分校（University of California San Francisco）的神經病學家和頭痛治療專家彼得•戈德比（Peter Goadsby）和他的同事發現，CGRP在偏頭痛發生時被釋放出來，而曲坦類藥物減少了CGRP的活動。

Several researchers and companies have been trying to develop drugs that bind to the CGRP receptors to prevent the chemical from activating the pain network. But because CGRP has a complex receptor - the slot where the molecule must bind in order to initiate actions in the body - it took chemists 15 years to figure out how to block the effects of CGRP, and even longer to develop a compound that could be taken orally, says Dr. Goadsby.
好幾家研究機構和公司一直在努力研發可以作用於CGRP感應器官的藥物，從而阻止這種化學物質激活疼痛網絡。但是戈德比醫生說，由於CGRP的感應器官非常複雜──藥物分子必須作用於這種感應器官才能激發身體的行動──藥物學家用了15年時間來研究如何阻止CGRP起效，而研製可以口服的藥物還要更長時間。

Bringing to market CGRP blockers, or antagonists - the most advanced of the new drugs in development for migraines - has proved challenging. Several investigational compounds have been shown to be toxic to the liver, a challenge that highlights the difficulty in developing drugs for conditions that affect the brain.
事實證明，面向市場推出CGRP阻滯藥物或者拮抗物──最先進的偏頭痛治療新藥──難度很大。好幾種正在研製中的藥物都被發現對肝臟有毒害作用，這項挑戰突顯了針對可影響大腦的病症開發藥物的難度有多大。

CGRP antagonists don't appear to work as well as triptans, but the blockers have an advantage in they don't appear to cause cardiovascular complications, says Stephen Silberstein, a neurology professor and director of Thomas Jefferson University's Headache Center in Philadelphia.
費城托馬斯•傑斐遜大學頭痛病研究中心（Thomas Jefferson University's Headache Center）的神經病學教授兼主任史蒂芬•西爾伯斯坦（Stephen Silberstein）說，CGRP拮抗藥物的療效似乎不如曲坦類藥物，但是阻滯類藥物的優點是它們似乎不會引起心血管併發症。

'You trade one kind of risk for another,' says Dr. Silberstein, who has served as an investigator on several companies' clinical trials.
“你是以一種風險來替代了另一種風險，”西爾伯斯坦醫生說。他擔任了好幾家公司產品臨牀試驗的調研員。

Merck & Co. had a promising CGRP-receptor antagonist under development but discovered in late-stage clinical-trial testing that some patients experienced liver enzyme changes. In July of last year, the company said it was discontinuing development of the compound, telcagepant, after looking at all its trial data. Germany's Boehringer Ingelheim GmbH was also working on a CGRP antagonist but canceled development. A spokesman declined to comment.
默克公司（Merck & Co.）曾經研製了一種讓人看好的CGRP感受器官拮抗藥，但是在後期的臨牀測試中發現，有些患者出現了肝臟 改變的情況。去年7月，該公司稱，在查看了所有試驗數據之後，公司不再繼續研製這種名爲telcagepant的化學藥物。德國的勃林格殷格翰製藥公司（Boehringer Ingelheim GmbH）也曾研製過一種CGRP拮抗藥，但後來終止了該產品的開發。一名發言人拒絕置評。

Bristol-Myers Squibb Co. is conducting several early stage studies on CGRP antagonists and other companies are testing or may begin development of similar compounds as well.
百時美施貴寶公司（Bristol-Myers Squibb Co.）正在進行幾種CGRP拮抗藥的早期研究，其它公司也在對類似藥物進行測試或者準備開始進行開發。

Researchers and companies also are trying to develop artificial antibodies that, when injected, would glom onto CGRP in the bloodstream or brain, before it reaches the receptors in the brain, or by blocking the receptors.
研究人員和企業也在努力開發人工抗體，注射進人體後，人工抗體會在CGRP抵達感應器官之前攔截血液或大腦中的CGRP，或者屏蔽感應器官。

Research into these biologic antibody-based approaches is at an earlier stage than the testing of antagonist drugs, but antibodies eventually might be able to block CGRP action regularly so that migraines don't ever begin.
對於這類基於生物抗體的方法的研究處於早期，還未達到拮抗藥物的測試階段，但是抗體也許最終能夠規律性地阻止CGRP的活動，使偏頭痛無從發作。

'The CGRP story is a story of developing an acute treatment for migraine,' says Dr. Goadsby. 'But the antibody story is testing the larger idea [that] if you blocked continuously CGRP, would you have a preventive treatment.'
“CGRP之說涉及到偏頭痛緊急治療方法的開發，”戈德比醫生說，“但是對抗體的研究實際上是就更重要的理念展開測試，即如果不斷阻止CGRP，就會是一種預防性的治療手段。”