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FEATURE ARTICLE
Current Progress in the Classication and Treatment of Headache
CAI Ding-fang () Headache is a general term for inward or outward cranial pain of various characters, and its classication is undoubtedly of fundamental meaning for differential diagnosis, and valid treatment of headache. The International Classification of Headache Diseases (Version 1)" (ICHD- ) has been issued by the International Headache Society in 1988. After then, the ICHD- was quickly universally accepted. Moreover, the new diagnosis standard for migraine worked out by Sulbactam Study was gradually applied in clinical practice. In the "International Classication of Headache (Version 2)" (ICHD-)(1) published in 2004, headache is classified into 4 kinds, namely, primary headache, secondary headache, and cranial neuralgia, central or primary facial pain, and others. Among them, primary headache, closely associated with neurology, is subdivided into 4 groups: migraine, tension type headache (TTH), cluster headache, and trigeminal autonomic cephalalgia. The recognition of headache by human being has gone through a long period of time. Headache was sorted into three kinds early in rst century A.D. by Aretaeus (81138), who named mild repeated headache as "cephalalgia", frequently attacking chronic headache as "cephalaea", and unilateral severe headache "heterocrania".(2) Christian Ludwig Baur, in 1787, classified headache into idiopathic headache and sympathetic headache, which were subdivided into some subtypes(3). In the 30s of the last century, Harold G. Wolff (18981962, USA) unfolded medical research on headache for the first time, and his chief contributions are (1) defined the sensory structure and radiating position of pain depending on various stimulating regions in the human brain; (2) verified the vascular dilation theory of migraine by the experimental study, and illustrated the relief of supercial arterial pulsation in the head by intravenous injection of ergotamine; and (3) put forward the concept of muscular contractive headache. His monograph on headache, "The man and his migraine", was published in 1948, which has been republished for seven editions and was called by the posterity as "Wolff's headache and other pain in the head"(4). In China, records of "Head Wind" is mentioned in the classic medical book, Huangdi Neijing, and the classication of headache has also been carried out by doctors in history from various viewpoints (5), as shown in Table 1. Migraine, the type of headache having been studied most frequently and deep, is one of the often encountered primary headaches, leading to loss of working capacity, ranked as the 19th of such diseases for causing disability in the world by WHO. However, what draws our attention is that no abnormality associated with the occurrence of migraine in the encephalic morphologic structure has been found so far, neither in modern medicine nor in Chinese medicine. Migraine is generally divided into two types depending on the emergence of presymptoms. Migraine without presymptom is a clinical syndrome characterized by headache accompanied with denite specicity and associated symptoms. Migraine with presymptom is characterized by the appearance of local neuro-symptoms with successive or concurrent headache. In some patients, the presymptoms reveal several hours or days before headache, with emergence of some atypical symptoms in the premonitory stage as well as in the onset stage, including excessive excitation, indolence, depression, longing for special food, repeated yawns, etc.
Zhongshan Hospital Affiliated to Fudan University, Shanghai (200032), China Tel: 86-13701645937, E-mail:dingfangcai@163.com DOl:10.1007/s11655-009-0243-4

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Chin J Integr Med 2009 Aug;15(4):243-247 Table 1. Historical Chinese Medicine Classication and Main Types of Headache
Time and source of the literature and their authors 400 BC Huang Di Nei Jing Yuan Dynasty Jin Dynasty Jin Dynasty Ming Dynasty Tang Dynasty Yuan Dynasty Ming Dynasty Ming Dynasty Ming Dynasty Wang Hao-gu Yi Lei Yuan Rong Li Gao Lan Shi Mi Cang Li Gao Nei Wai Shang Bian Huo Lun Zhang Jing-yue Jing Yue Quan Shu Wang Shu-he Mai Jing Wang Tao Wai Tai Mi Yao Wei Yi-lin Shi Yi De Xiao Fang Wang Ken-tang Zheng Zhi Zhun Sheng Fang Yu Yi Lin Sheng Mo Zhang Jing-yue Jing Yue Quan Shu

Sort and main types Classied depending on Jingluo Sanyang and yin-syndrome headache Taiyin, Jueyin, and Shaoyin headache Classied depending on etiology Exogenous headache Wind headache Pestiferous headache Summer-heat headache Stinky toxic headache Dampness headache Exogeneous injury caused headache Fainting headache Phlegm caused headache Sots' headache Dyspeptic headache Asthenic headache Fire headache Other headache Unendurable headache Thunder headache Severe Thunder headache Light Thunder headache Prolonged headache Blood-stasis caused headache

West Jin Dynasty

400 BC Nei Jing-Ling Shu Ming Dynasty Fang Yu Yi Lin Sheng Mo Ming Dynasty Wang Ken-tang Zheng Zhi Zhun Sheng Ming Dynasty Dai Yuan-li Zheng Zhi Yao Jue Ming Dynasty Dai Yuan-li Zheng Zhi Yao Jue Ming Dynasty Zhang San-xi Yi Xue Zhun Sheng Liu Yao 400 BC Nei Jing-Ling Shu 400 BC Nei Jing-Su Wen Ming Dynasty Wang Ken-tang Zheng Zhi Zhun Sheng Ming Dynasty Wang Ken-tang Zheng Zhi Zhun Sheng Ming Dynasty Fang Guang Dan Xi Xin Fa Fu Yu Qing Dynasty He Meng-yao Yi Bian

The clinical specicities of migraine are repeated attacks of unilateral, pulsatile headache to moderate or severe degree, lasting for 4-72 h, and it can be aggravated by daily labor, accompanied with nausea, vomiting, and/or intolerance of light and sound. Its diagnosis criteria are as follows: (1) having suffered from at least five attacks and meeting the criteria listed in (2) and (4); (2) the attack of headache lasting for 472 h (when untreated or when treatment failed in the treatment); (3) headache shows at least two of the following specificities: (a) unilateral, (b) with pulsation, (c) of moderate or severe degree, (d) could be aggravated by or may lead to forced avoidance of daily physical activities, such as taking a walk or climbing stairs; (4) coexistence of nausea and vomiting and/or intolerance of light and sound; and (5) not caused by other diseases. According to the Guidelines for Migraine issued by the United States Headache Confederation (USHC) and published by the Quality Standards Subcommittee of the American Academy of Neurology in 2000,

the treatment of migraine is divided into the acute treatment (for the attack stage) and the preventive treatment (for the relief stage). The goals of acute treatment are to alleviate headache rapidly and to prevent relapse, as well as to restore the normal living capacity of patients, etc. The specific drugs as Triptans (5-HT1b/1d receptor agonists) and dihydro-ergotamine could effectively treat patients of moderate/severe degree or those with mild/moderate headache responding poorly to nonspecific drugs; the per-oral nonsteroid anti-inflammation drugs (NSAIDs), like aspirin, are regarded as the first used drug for attacks of mild/moderate migraine. To prevent drug induced headache, the medication in the attack stage is generally applied only in patients with headache attacks that last for 2 days in a week. The drugs for acute treatment of migraine are shown in Table 2(6). The goals of preventive treatment are to reduce the frequency, severity, and duration of attacks, to

Chin J Integr Med 2009 Aug;15(4):243-247 Table 2.

Group 1 Specic Naratriptan PO Rizatriptan PO Zolmitriptan PO DHE SC, IM, , IN Group 2 Acetaminophen plus codeine PO

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Drugs for Acute Treatment of Migraine

Group 3 Butallital, aspirinm, plus caffeine PO Group 4 Acetaminopjen PO Chlorpromazine IM Granisetron Lidocaine Group 5 Dexamethasone Hydrocortisone

Butalbital, aspirin, caffeine, Ergotamine PO plus codeiniPO Butorphanol IM Diclofenac K, PO Ergotamine plus caffeine plus Bellafoline PO Isometheptene CPD, PO Ergotamine plus caffeine PO Metoclopramide IM, PR

Sumatriptan SC, IN, PO Chlorpromazine IM,

DHE , plus antiemetic Flurbiprofen, PO Nonspecic

Acetaminophen, aspirin, Ketorolac IM plus caffeine PO Aspirin PO Butorphanol IN Ibuprofen PO Naproxen sodium PO Prochlorperazine Lidocaine IN Meperidine IM, Methadone IM Metoclopramide Naproxen PO Prochlorperazine IM, PR 1. Proven, pronounced statistical and clinical benet (at least two double-blind, placebo-controllled studies and clinical impression of effect). 2. Moderate statistical and clinical benet (one double-blind, placebo-controlled study and clinical impression of effect). 3. Statically but not proven clinically, or clinically but not proven statistically effective (conicting or inconsistent evidence). 4. Proven to be statistically or clinically ineffective (failed efcacy versus placebo). 5. Clinical and statical benets unknown (insufcient evidence available).

enhance the sensitivity of patients to acute treatment, and to improve function and lessen disability in patients. Medication of preventive treatment is indicated to (1) presence of over two attacks in a month with disability for over three days; (2) when acute treatment is ineffective or patients are contraindicated to or intolerable of adverse reaction resulting from the treatment; (3) having terminated attacks for over two episodes in a week; (4) special types of migraine, such as the hemiplegic type of migraine, the basilar type of migraine, migraine with prolonged aura, and the episode might cause permanent injury to nerve function such as migrainous cerebral infarction; (5) menstrual migraine; and (6) patients prefer it(7). The principle of preventive treatment is to initiate the treatment at low dose of confirmed effective drugs, but the dosage might be increased gradually; 2-3 months application of a drug is necessary to estimate its clinical effectiveness. Then, it is to avoid interfering medication (excessive use of drugs for acute treatment); and the long-acting preparation is the first choice. A daily record of the headache may

be created for monitoring the changes of headache in patients and evaluating the efficacy of treatment; lessening the dose or discontinuing the medication is allowable only after the headache is completely alleviated for 3-6 months. The occurrence of some complications, like stroke, myocardial infarction, Raynaud's phenomenon, epilepsy, affective, and anxiety, should be taken into full consideration, which may be the treatment opportunities, and also the limitations of drug choice. The principle of medication for co-existing diseases and complications are as follows: selecting drugs as those effective to both the migraine and the complication as possible; guaranteeing not to choose drugs contraindicated to complications or drugs that could induce or aggravate migraine; paying attention to the interaction among drugs; and treating pregnant women or women ready to get pregnant, what should be selected are drugs with the least adverse effect on fetus. The drugs for preventive treatment of migraine are listed in Table 3(7). Chinese medicine has a long history in treating

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Chin J Integr Med 2009 Aug;15(4):243-247 Table 3. Drugs for Preventive Treatment of Migraine
Group 3 A: Antidepressants Doxepine Fluvoxamine Group 4 Methysergide Group 5 Acebutolol Carbamazepine Clomipramine, clonazepam Clonidine Ca-blockers Nimodipine/verapamil NSAIDs Aspirin/fenoprofen/ urbiprofen Ketoprofen Mefenamic acid Neproxen Naproxen sodium Imipramine Mirtazepine Nortriptyline Paroxetine Probtriptyline Sertraline trazodone Venlafaxine Cyproheptadine Diltiazem Ibuprofen Tiagabine Topiramate Others Feverfew Magnesium vitamin B2 B: (side effect concerns) Methylergonovine (methylergometrine) Phenelzine Clonidine Indomethacin Nicardipine Nifedipine Pindolol

Group 1 Amitriptyline Divalproex sodium Fropranolol/timolol Fluoxetine (racemic) Gabapentin

Group 2 -lbockers Atenolol/metoprolol/nadolol

1 Does not include combination products. 2 Medium to high efcacy, good strength of evidence, and mild-to-moderate side effects. 3 Lower efcacy than those listed in the rst column, or limited strength of evidence, and mild-to-moderate side effects. 4 Clinically efcacious based on consensus and clinical experience, but on scientic evidence of efcacy. 5 Medium to high efcacy, good strength of evidence, but with side effect concerns. 6 Evidence indicating no efcacy over placebl.

headache, with rich clinical experience accumulated. For example, Wuzhuyu Decoction () used for treating "headache with nausea and running saliva" was recorded in Shang Han Lun () by ZHANG Zhong-jing; Dachengqi Decoction ( ) was offered for treating hemilateral headache in Ru Men Shi Qin ( ) written by ZHANG Zihe, and in Dan Xi Xin Fa ( ), ZHU Dan-xi recommends Qing Kong Paste () for protracted frontal or partial headache, etc. At present, patent Chinese drugs such as Duliang Soft Capsule ( , containing dahurian angelica and chuanxiong), Yangxue Qingnao Granules (, containing angelica, chuanxiong, white peony root, wild ginger, etc.) are widely applied for acute and preventive treatment of migraine, which have shown certain effects. However, we hold that it is very important to select rationally and scientifically the primary and

secondary criteria of therapeutic efficacy evaluation in developing clinical trials on migraine. The criteria for evaluating therapeutic effect on acute attacks of migraine observed by Olesen J, et al(8) are: primary criteria refer to 2 h responsive rate, namely, the percentage of patients with headache disappeared or reduced to mild degree within the rst 2 h of treatment; secondary criteria refer to (1) the 30-min, 1-, 2-, 4-, and 24-h responsive rate and complete remission rate; (2) the 24-h sustaining responsive rate; (3) remission rate of accompanied symptoms such as nausea, vomiting, intolerance of light and sound, etc.; (4) degree of disability; (5) conditions in which other analgesics are needed; and (6) incidence of adverse reaction. The criteria for preventive treatment issued by Magis D, et al(9) are: primary criteria refer to the frequency of attacks, and the percentage of patients with their attacks reduced by 50%; secondary criteria

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refer to the total number of days during which the patients suffer from migraine in a month; severity and duration of attacks; the total number of days with nausea and vomiting; and the amount of antimigraine agents taken each day in the attack period. The standards of classification and therapeutic efficacy evaluation are very important for the investigation of headache. The International Headache Society stressed its disapproval of publishing articles concerning headache that do not keep to or refer to its standards. On this account, the author proposes that at the same time of accepting and using the ICHD-, the standard for efcacy evaluation should be implemented seriously and accurately to make the clinical design strict, so as to elevate the level of Chinese medicine and integrative medical researches on headache in China.

3.

Gladstone JP, Dodick DW. From hemicrania lunaris to hemicrania continua: an overview of the revised International Classification of Headache Disorders. Headache 2004;44: 692-705.

4. 5. 6.

Blau J. Harold G Wolff: the man and his migraine. Cephalalgia 2004;24:215-222. LI WW, CAI DF. History of taxonomy of headache. Chin J Med His (Chin) 2005;35:230-234. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:754-762.

7.

Snow V, Weiss K, Wall EM, Mottur-Pilson C. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med 2002;137: 840-849.

8.

Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, et al. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 2004;350:1104-1110.

REFERENCES
1. Lima MM, Padula NA, Santos LC, Oliveira LD, Agapejev S, Padovani C. Critical analysis of the international classification of headache disorders diagnostic criteria (ICHD I-1988) and (ICHD II-2004), for migraine in children and adolescents. Cephalalgia 2005;25: 1042-1047. 2. Koehler PJ, van de Wiel TW. Aretaeus on migraine and headache. J Hist Neurosci 2001;10: 253-261. 9.

Magis D, Ambrosini A, Sandor P, Jacquy J, Laloux P, Schoenen J. A randomized double-blind placebo-controlled trial of thiotic acid in migraine prophylaxis. Headache 2007;47:52-57. (Received April 3, 2009) Edited by GUO Yan