Knowledge Mapping of Migraine: a Bibliometric Analysis (2000-2019)


 Background: There has been rapid development of migraine research in the past 20 years in China and around the world. We analyzed the development trend of migraine research, and made a bibliometric analysis on the growth trend of the total number of publications, countries, institutions, authors, cited references and keywords from 2000 to 2009 and 2010 to 2019 by applying visualization software, and constructed the relevant knowledge map, and found the trends and hot spots in the field through comparison. Methods: Retrieved the literature on migraine in the Web of Science database from 2000-2009 and 2010-2019 respectively, and then utilized CiteSpace to conduct bibliometric analysis to acquire the knowledge mapping. Results: The total number of publications each year has increased year by year, and the average annual growth rate from 2000 to 2009 was 7.999%, while from 2010 to 2019 was 5.348%, with a faster growth rate from 2000 to 2009. According to the cluster analysis of institutions, authors, cited references, and keywords, 10/11, 12/11, 12/11, and 8/9 categories were obtained from 2000 to 2009 and 2010 to 2019 respectively. The most productive countries, institutions, and authors are the USA, Albert Einstein College of Medicine, and Lipton RB from 2000 to 2009 and 2010 to 2019, whose frequency is 4274/7107, 322/592, and 279/472 respectively. However, the most important of them are Belgium/ Pakistan, Houston Headache Clin/ Amgen Inc, and Lipton RB/ Klatt J, owing to their highest centrality, they are 1.20/1.08, 1.13/1.32, and 1.22/0.89 separately. Moreover, Cited references that contributed to the most co-citations are Silberstein SD (2004)/ Bes A (2013) from 2000 to 2009 and 2010 to 2019, however, the most vital cited reference is Welch KMA (2001)/ Goadsby PJ (2017). Keywords such as migraine, headache, prevalence, and the double blind are the most frequently used. But prevalence is the crucial keyword. In the cluster analysis of institutions, authors, cited references, and keywords from 2000 to 2009 and 2010 to 2019, the more convincing research categories are potential anti-migraine agent/ chronic migration prevention, reducing headache recurrence/ following symptomatic treatment, to-left shunt/ placebo controlled phase, spectrum study/ family study hemiplegic migraine, with S values of 0.952/0.956, 0.985/0/986, 0.981/0.970 and 0.985/0.982 respectively. Furthermore, the hotspots in this field are “stimulation”, “triptan” from 2000 to 2009 and 2010 to 2019. Conclusion: Based on the bibliometric analysis in the past 20 years, the knowledge mapping of the country, institution, author, cited reference, and the keyword is gained, which has an important guiding significance for quickly and accurately positioning the trend in this field.


Introduction
Migraine is a group of recurrent headache disease, showing unilateral or bilateral pain, often accompanied by nausea and vomiting. A few typical cases have visual, sensory, and motor disorders and other auras before the attack [1], and may have a family history [2]. According to a study of the 2016 global burden of disease study, 1.04 billion people worldwide suffer from migraine, with an overall prevalence rate of 14.4% [3]. Migraine affects women three times as much as men [4]. The prevalence of migraine in children increases with age [5]. And the annual prevalence of migraine in the elderly is about 10% [6]. Migraine is the main cause of disability in the world, the number of years of disability-adjusted life lost caused by migraine has reached one third [7]. With the increase of headache days, the disease burden (disability, medical care utilization, and direct cost) of migraine patients also increases [8]. The high incidence rate, high disability rate, and the increase of treatment expenditure have brought serious economic costs and brought various burdens to society. It is vital to quickly and accurately grasp the research trends of migraine.
Bibliometrics is an interdisciplinary science that uses mathematical and statistical methods to quantitatively analyze all knowledge carriers. It uses statistical indicators to measure the contribution of a research eld [9], including different countries, institutions, journals, or authors and predicts trends or hotspots in a eld [10]. The research methods involved include co-word analysis and cluster analysis. Co-word analysis is an important method of bibliometrics [11]. It can be used to identify trends and hotspots. The number of occurrences in the group of literature, this number of co-occurrences to measure the close relationship between them. Cluster analysis utilizes weighting algorithm, log-likelihood algorithm, and mutual information algorithm with "title entries", "index entries", and "abstract entries" to extract common information to interpret research mainstreams and research characteristics [12]. Researchers rely on relevant analysis software for visual analysis (including Citespace [13], VOSviewer [14], Histcite [15], etc.).
To date, there has been no comprehensive article of studies on migraine using bibliometric methods. Therefore, in this study, to analyze the global status and trend of migraine in the past 20 years, the researchers used the bibliometric software CiteSpace to not only analyze the growth of publications in this eld from 2000 to 2019 of the web of Science Database (SCI-E), but also construct the knowledge maps of countries, institutions, authors, cited references and keywords from 2000 to 2009 and 2010 to 2019, and compare the differences and connections between them, which is of great signi cance to accurately grasp the research trends and hotspots.

Source of literature
To prevent the omission of searching the literature, we used "migraine" to search for synonyms in the MeSH Database, the subject word database in Pubmed, and then merge the nal data. Firstly, we input the Web of Science database with English Subject words= "migraine". Next is Web of science database settings: Literature was retrieved online through the Science Citation Index-Expanded of the Web of Science Core Collection on November 18, 2020 [16], and the language of the literature is not to deduplicate literature, secondly, two researchers were required to check before and after literature deduplication. These two researchers separately examined the papers by title, abstract, and full text. And the searched Web of science database comes from the Tsinghua University Library database in China.

Analysis software
The version of Citespace analysis software is 5.2.R1, which was invented by Professor Chen Chaomei from the Computer and Information Science of Drexel University in the United States, and can be used to analyze the structure, laws, and distribution of scienti c knowledge [17].

Download and import of data
The results retrieved by subject words are exported, and the le format is "plain text". The researchers used Citespace software to remove duplicates and kept a unique record, and then analyzed it.

Parameter setting
Time slicing (from 2000 to 2009 and from 2010 to 2019, years per slice: 2), node type (check one at a time, including Author, Institution, Country, Keyword, Cited Reference), selection criteria (TopN, select top 50 levels of most cited or occurred items from each slice), pruning select Path nder, and Pruning the merged network. Because the network obtained by keywords is messy in 2010-2019, Therefore, the network screening measures of keywords are as follows: years per slice: 2, the keyword analysis should also select pruning sliced networks.

Statistical methods
The statistics of the total number of publications in the two stages were analyzed by SPSS 24.0, and the measurement data is expressed by the mean ± standard deviation. If it is following the normal distribution, the comparison of the means between the two groups is performed by t-test. Relying on GraphPad Prism 8 to perform linear regression analysis on the total number of publications. And the difference is statistically signi cant with P<0.01. The scientometric analysis was executed on all literature of acupuncture for cancer pain, the frequency of which is mainly utilized to observe the core countries/territories, institutions, authors, cited references, keywords. And Centrality is an indicator to measure the importance of nodes in the network, to discover and measure the signi cance of the literature. The result of clustering analysis is a keyword co-occurrence network. This network can re ect the current and past research hotspots in a certain eld. Cluster view shows the distribution of research elds from different angles. Based on the network structure and the clarity of clustering, Citespace provides two indicators: the module value (referred to as Q value) and the silhouette value (referred to as S value), as the basis for us to judge the effect of map drawing, the silhouette value is the average that the contour values of each sample point. Generally speaking, the Q value is generally in the interval [0,1), and Q>0.3 means that the divided community structure is signi cant; when the S value is 0.7, the clustering is highly e cient and convincing, if it is 0.5 above, clustering is generally considered reasonable [18]. And the interpretation of cluster analysis results mainly includes Cluster ID, Mean Year, Size, Silhouette, Label (LLR), Label (MI). Cluster ID is the number after clustering, and Size represents the number of members contained in the cluster. The larger the Size, the smaller the number. Mean Year represents the average year of the literature in the cluster, which can be used to judge the distance of the cited literature in the cluster. The larger the log-likehood ratio (LLR), the more representative of the cluster category; mutual information (MI) is mainly used to represent the relationship between terms and categories in text mining, and it does not consider the frequency of feature words. The timeline view mainly shows solicitude for delineating the relationship between clustering results and focuses on the historical span of documents in a clustering result.

Analysis of the total number of publications
The variable of the total number of publications in the two time periods was found to obey a normal distribution through P-P chart analysis. Therefore, the comparison of the two means found that P = 0.000128 < 0.01 (Table 1) Table 1), the Pearson r correlation coe cient = 0.9348, P < 0.0001, indicating that it is greater than 99.5% Con dent that the correlation coe cient reaches 0.9348, X and Y are linearly related; while the linear regression equation for 2010-2019 is Y = 101.7X + 1455 ( Fig. 1 and Table 1), the Pearson r correlation coe cient = 0.8713, and P = 0.001 < 0.01, indicating that it is greater than 99.5% Con dent that the correlation coe cient reaches 0.8713, X and Y are linearly related.    Table   3. When the cluster view can't judge which institutions focus on the same research in detail, it will utilize the cluster timeline view prevention, 3 temporomandibular disorder, 4 patient-reported outcome, 5 ampp study, 6 systematic review, 7 depressive disorder, 8 pressure algometry data, 9 chronic migraine and 10 childhood maltreatment. The silhouette of all the clustering results was greater than 0.7, which indicates that the results of all categories of cluster analysis are very reliable. Also, the most important research categories in the two periods were a potential anti-migraine agent and headache care.

Distribution of authors and Cluster analysis
The distribution of the main scholars engaged in migraine is shown in Table 4. and Lipton RB (centrality = 0.78), therefore, they are considered to be the most important researcher in the Author's network relationship.  The knowledge base and research progress of migraine are described using high co-citation references and main article clusters respectively, and the co-citation frequencies of references and their importance in network nodes are shown in Table 4. The     (844), and sumatriptan (754). But from the perspective of centrality, the most vital keyword in the network is migraine (centrality = 1.45), followed by sumatriptan (centrality = 0.97), prevalence (0.96), headache (0.85), aura (centrality = 0.65). Thus, compared with the rst stage, migraine, headache, prevalence, double blind were also in the top four, only increasing in number. And the most critical keywords are the same as the previous period, which is migraine (centrality = 1.56). The next four different keywords are double blind (centrality = 1.07), prevalence (centrality = 0.71), aura (centrality = 0.42), and gene related peptide (centrality = 0.38). Therefore, these keywords constitute the main content of migraine research.  Figure 6 and Table 8   Burst is used to re ecting hotspots within a certain time node. The red bar indicates the duration of the citation explosion and the start and end year that the citation explosion. That is to say: the red bar indicates some frequently cited keywords, and the green bar is rarely cited in terms of keywords [23], it was found that the hotspot of migraine between 2000 and 2009 was "stimulation". And from 2010 to 2019, the hotspot of migraine was "triptan". The speci c results are shown in Fig. 7.

Discussions
In  [24], migraine epidemiology and health care model in the United States [25], and migraine prevalence in Taipei (China) [26]. And the 2010-2019 study is more inclined to the treatment of children's migraine [27], chronic pain, and depression in the quality of life of migraine women [28].
Cluster analysis of authors from 2000 to 2009: #1 menstrual migraine: First, the relationship between the menstrual cycle and headaches of migraine patients were explored, and it was con rmed that migraine attacks without aura were more likely to occur 2 days before the start of menstruation and 2 days before the menstrual cycle [29]. Secondly, it was found that rizatriptan can effectively treat menstrual-related migraine attacks [30]. All these provide a good research basis for the diagnosis and treatment of menstrual-related migraines. #2 migraine prevention: In this category, the prevention of migraine is mainly based on drugs, and the representative drug is naratriptan. Related results indicate that if 2.5 mg of naratriptan is taken in the early stage of prodromal symptoms, it is more effective to prevent headaches and the severity of headaches will be greatly reduced, which provides a medication basis for the early prevention of migraine [31]. #3migraine patient: Through the comparative analysis of visual and auditory cortex evoked potentials in migraine patients, it is found that the increased migraine response may be due to the decreased pre-activation level of the sensory cortex [32]. #4 disintegrating tablet: A Phase 3 crossover study on the pharmacokinetic characteristics of 10 mg rizatriptan tablets and orally disintegrating tablets in healthy subjects proved that the absorption rate of rizatriptan orally disintegrating tablets was slightly slower than that of its tablets, and the bioavailability and peak concentration were similar [33], which supplied a reference method for the study of the absorption rate on different dosage forms of drugs. #6 medication overuse: This category engrosses in the follow-up study of overuse of analgesics in the treatment of migraine. In the follow-up study after 3 years of overuse of analgesics, the combination of drugs and biofeedback therapy is more effective than drug therapy alone [34], which provides a new treatment model for migraine. Overuse of analgesics for 1 year indicates that chronic migraine accompanied by overuse of analgesics leads to severe disability before treatment [35]. #7 cardiovascular disease: This category mainly discusses the relationship between migraine and cardiovascular disease.
Studies have shown that TT genotype carriers have an increased risk of cardiovascular disease in migraine patients with aura [36], while researches in female migraine patients have found that active migraine with aura is associated with an increased risk of cardiovascular disease, active migraine without aura is not associated with an increased risk of cardiovascular events [37]. This is a good exploration from the correlation research of risk factors. #8 chronic daily headache: The research in this category mainly includes two aspects of the main life changes before and after the onset of chronic daily headache and the identi cation of chronic daily headache and related factors of induction and transformation. A proportional control study found that chronic daily headache cases are more likely to experience certain major life events within 2 years before the chronic daily headache attack than episodic headaches, especially in middle-aged people over 40 years [38]. In addition, the transformation of past occasional headaches or the occurrence of new daily persistent headaches may be related to certain medical conditions and behaviors [39], providing a basis for the analysis of related factors of induction and transformation. #9 human isolated blood vessel: Eletriptan and sumatriptan contract the middle meningeal artery more than the coronary artery [40], which provides a basis for the rational drug choice for migraine. #10 alternating hemiplegia: Alternating hemiplegia in children is a rare disease, which is often associated with migraine. CACNA1A gene on chromosome 19 is related to familial hemiplegic migraine and other paroxysmal brain diseases. The mutation of the CANA1A gene is expected to increase the concentration of K+ and glutamate in synaptic space, and increase the release of neurotransmitters, which is the mechanism of alternating hemiplegia and migraine in children [41]. Haan J [42] found that the second comorbid gene is ATP1A2, which is the common pathogenesis of alternating hemiplegia and migraine in children. Cluster analysis of authors from 2010 to 2019: Chronic migraine: #0 and #9 are included in this category, Oral botulinum toxin not only signi cantly reduced the number of days of headache and migraine but also improved the quality of life for patients and avoided the overuse of painkillers [43]. #2patient-reported outcome: Focusing on patient outcomes in migraine prevention, Pompili M's study [44] found that a combination of comprehensive care and preventive treatment for adult migraine patients may be the best choice for migraine improvement. Adequate prevention is especially critical in reducing disability and preventing migraines from evolving. #4American migraine prevalence: Compared with episodic migraine, patients with chronic migraine have signi cantly lower family income levels, and patients with chronic migraine are about twice as likely to suffer from depression, anxiety, and chronic pain [45]. In addition to the difference in the frequency of headache attacks, chronic migraine, and paroxysmal migraine are also the key to distinguish between the two. #5 preempt clinical program: The PREEMPT study for migraine prevention and treatment includes two phases, PREEMPT 1 and PREEMPT 2, which are used to evaluate the effectiveness, safety, and tolerability of botulinum toxin for preventing migraine in adults. The results of the research indicate that repeated botulinum toxin treatment is Safe and well tolerated [46]. #6 medication-overuse headache: This category mainly includes abnormal cortical responses to somatosensory stimulation in patients with drug overuse, risk factors, headache management, and personality characteristics of drug overuse headaches and episodic headaches. Coppola G's research [47] suggests that overuse of non-steroidal anti-in ammatory drugs In patients, the somatosensory cortex becomes more and more sensitive, which is conducive to compulsive drug intake behavioral sensitization; Sances G [48] believes that the negative prognostic factors for headache recurrence include intake of more than 30 doses per month, smoking, drinking, etc., which are dangerous Factors may in uence treatment strategies. Tassorelli C [49] advocated that the consensus solutions proposed in different countries and different medical models have been proven effective for headaches caused by drug overuse. Sances G [50] found that MMPI-2 tracked the psychological characteristics of headache patients well, but he was not sure whether it was related to MMPI 2 "itself". #7 genome-wide association study: In his genome-wide association study, Anttila V [51] identi ed that the minor allele of rs1835740 on chromosome 8q22.1 was associated with migraine, and also found that rs1835740 was the rst genetic risk factor for migraine, which provided evidence for understanding the disease from the genome-wide perspective. Cluster categories that are not discussed in the article indicate that this category has no special signi cance, or that there are few related documents in this category, or that no similar research reports have been found. that the Periaqueductal gray matter may play a role as a "producer" in migraine attacks, while Goadsby PJ's study showed that the monthly subcutaneous injection of erenumab 70 mg or 140 mg could signi cantly reduce the frequency of migraine attacks and cut down the use of speci c drugs for acute migraine within 6 months.
According to the cluster analysis of cited references, the common research in the two periods is chronic migraine. The difference between the two is: the study of chronic migraine in 2000-2009 mainly focused on the diagnostic criteria of the disease [52] and topiramate can decrease the headache days of patients with chronic migraine [53], while 2010-2019 focused on the disability, quality of life, sociodemographic [45] and comorbidity characteristics [54] of patients with chronic and intermittent migraine. By comparing #6 Migraine headache in 2000-2009 with #11 familial migraine in 2010-2019, the research content is mainly for familial hemiplegic migraine, but the previous period involved mainly gene mutations [55] and genes Localization [56], chromosome markers, and the latter mainly focused on genome-wide associations, con rming that the minor allele of rs1835740 on chromosome 8q22.1 is related to migraine [57]. The similarities and differences between the two periods in terms of neuronal channels are: A Ducros's study [58] found that hemiplegic migraine caused by mutations in CACNA1A (a gene encoding neuronal calcium channels) has a broad clinical spectrum, including paroxysmal and permanent. Signs, the severity of the two are very different, and Martin Dichgans's research [59]found that a new site of familial hemiplegic migraine was found on chromosome 2q24. Sequencing of candidate genes in this region revealed a heterozygous missense mutation (Gln1489Lys) in the neuronal voltage-gated sodium channel gene SCN1A, which is related to epilepsy. The same mutation appeared in three familial hemiplegic migraine families. It results in a charge-change amino acid exchange in the so-called hinge domain of the protein, which is essential for the rapid inactivation of the channel. These studies provide us with methodological reference for randomized controlled trials of drug treatment on migraine from different levels. 2 economic outcome: The main study is the burden of migraine disability and economic loss in the United States [63]. The bed rest time of migraine patients takes up the working day and impairs work function, causing US employers to lose about 13 billion U.S. dollars and the annual direct cost of care is about 1 billion U.S. dollars. Therefore, the economic burden of migraine is mainly concentrated in bed rest and productivity declines, which in turn greatly affects employers' economic income, various screening and treatment options should be evaluated to reduce the burden of disease. 5 headache sufferers study: Mainly include the prevalence of migraine in different countries, the diagnosis mode, and preventive treatment of migraine. It was found that in the past ten years, the prevalence of migraine in France was 11.2% for women and 4.0% for men [64]. In the United States [65], the prevalence of migraine was 18.2% for women and 6.5% for men. The MIDAS score is lower than the score obtained in the US population study. This is helpful for us to understand the epidemiological results of migraine in different countries and to judge the clinical characteristics. 8 chronic daily headache: This category of research mainly focuses on the epidemiological analysis of chronic daily headaches in the general population and the related factors of onset and relief. Castillo J's research [66] found that almost 5% of the general population suffers from chronic daily headaches. The proportions of chronic tension-type headaches and conversion migraines are very similar. A.I. Scher's study [67] con rms that chronic daily headaches are more common in women and have lower levels of education. It is more common among low-income people, white people, and married people. Its prevalence is related to obesity, arthritis, and diabetes. 9 trigeminovascular system: The main research in this category is that the intrinsic brain activity in the migraine model triggers trigeminal meningeal afferents. Hayrunnisa Bolay's research [68] found that the trigeminal nerve innervates the meninges and participates in migraine. Cortical diffusion inhibition leads to selective and persistent enhancement of blood ow in the middle meningeal artery, which provides a basis for the mechanism of migraine and a good interpretation of vasodilation in migraine. 10 using rizatriptan: The research in this category mainly shows solicitude for the application of rizatriptan in the acute treatment of migraine. Rizatriptan produces a consistently high response rate in the acute treatment of migraine attacks [69]. Comparing with sumatriptan, naratriptan, and zolmitriptan, it was found that rizatriptan eliminated a signi cant proportion of patients' disability within 2 hours. It provides a basis for the selection of drugs for migraine treatment. 11 to-left shunt: The research in this category mainly concentrated on the relationship between migraine with aura and cardiac shunt from right to left, and the relationship between patent foramen ovale or atrial septal defect and the incidence of migraine. First of all, P Wilmshurst's research [70,71]shows that there is a causal link between the right-to-left shunt of the heart and migraine with aura, and the closure of atrial defects can improve or eliminate migraine. Secondly, Babak Azarbal's study [72] further con rmed that occlusion of patent foramen ovale or atrial septal defect via catheter can completely relieve migraine symptoms in 60% of patients, providing a new method for the treatment of migraine. Cluster analysis of cited references from 2010 to 2019: 1 excitatory-inhibitory balance: The focus of the research in this category lies in the clinical relevance of cortical diffusion inhibition in neurological diseases [73] (including migraine). The cortex of migraine patients is thought to be over-excited due to impaired habit, which may explain why the patient Increased susceptibility to cortical diffusion inhibition, therefore, patients with familial hemiplegic migraine may show a particularly low threshold for cortical diffusion inhibition. 3 new analysis: The research in this category mainly includes the following aspects: updated guidelines for drug treatment to prevent adult-onset migraine [74], the latest statistical analysis of the prevalence and burden of migraine and severe headache in the United States [75], and evidence of acute treatment of adult migraine Evaluation [76]. The results show that valproate sodium, valproate sodium, topiramate, metoprolol, propranolol, and timolol are effective in preventing migraine, and can reduce the frequency and severity of migraine attacks; In the United States, the prevalence of migraine is very high, about one in seven people suffer from this disease each year. Migraine and headache are the main reasons for outpatient and emergency visits; triptans, ergotamine derivatives, NSAIDs, opioids, and combination drugs Effective for acute treatment of migraine. These studies have not only conducted in-depth discussions on migraine from the perspective of epidemiology but also the perspective of disease prevention and treatment, to guide clinicians in the precise treatment of migraine. 5 placebo effect: Studies in this category are mainly randomized, double-blind, placebo-controlled researches. The drugs involved mainly include botulinum toxin [43] and topiramate [53]. Botulinum toxin sodium has obvious advantages in curative effect, reducing disability, and improving function and related quality of life. Topiramate can signi cantly reduce the number of days of migraine per month, which provides medication guidance for the prevention of migraine. 6 emerging drug: This category of research is mainly based on randomized controlled trials of human monoclonal antibodies in the prevention and treatment of paroxysmal migraine. The drugs involved mainly include fremanezumab [77] and erenumab [22]. Subcutaneous injection of fremanezumab can reduce the number of migraine days per month by an average of 1.3 to 1.5 days within 12 weeks. Subcutaneous injection of 70 mg or 140 mg of orrenzumab per month can signi cantly reduce the frequency of attacks and reduce the use of speci c drugs, which provides a basis for the prevention and treatment of migraine from the perspective of monoclonal antibody. 8 calcium channel function: Familial hemiplegic migraine type 1 calcium channel mutations cause increased cortical neurotransmission excitability, indicating that the destruction of excitatory-inhibitory balance and neuronal overactivity is the basis for migraine attacks susceptible to cortical diffusion inhibition ignition [78]. 9 key player neuropeptide: This category mainly introduces the pathophysiological basis of calcitonin gene-related peptide and its receptor triggering migraine [79,80]. This peptide is found in small and medium-sized neurons of the trigeminal ganglion and is released from the sensory nerves. Therefore, it is related to the pain pathway. It is released during migraine attacks and can cause migraines. It provides us with ideas for the development of new drugs to treat diseases from our understanding of this molecule.

Keywords' cluster analysis comparison
By comparing the cluster analysis of keywords in the two time periods, we found that the following research categories to-left shunt, chronic migraine, and familial hemiplegic migraine have all been analyzed in other cluster analysis, so we only discussed the cluster categories that did not appear. Cluster analysis of keywords from 2000 to 2009: 1 trigeminal ganglion cell: In this category, the expression of 5-HT 1B receptor in rat trigeminal ganglion cell subtypes was mainly studied, 5-HT 1B receptor agonists can reduce neurogenic vasodilation by activating this receptor, which helps explain the anti-migraine drugs and accelerate the development of compounds that speci cally act on vascular or neural receptors [81]. 2 common experience: Perquin CW's research [82] concentrates on the clinical epidemiology of pain in children and adolescents. Research has shown that chronic pain (including migraine) is a common problem in children and adolescents, especially severe chronic pain and multiple pain in girls 12 years and older. The high incidence of the disease should become the main focus of future health care services. The enlightenment for follow-up research is to focus on the pain process, quality of life, and biological-psychological-social factors over the years, which will be potential targets for intervention. 3 cytokine level: This type of research is represented by the plasma cytokine levels of migraine patients. By collecting the plasma of migraine patients and healthy people, using enzymelinked immunosorbent assay to detect cytokine levels, the study found that tumor necrosis factor-alpha (TNFα), IL-1β, and IL-10 may be involved in the onset of migraine [83]. 4 sumatriptan tablet: This category mainly analyzes the cost-effectiveness of sumatriptan tablets and conventional therapies in the treatment of migraine. The results of the study show that the net bene t of sumatriptan in treating a single migraine attack is $50, while the net bene t of conventional therapy is $20. And compared with the annual increase in net income, sumatriptan is 114-540 US dollars per patient more than conventional treatment. It further demonstrates that the advantages of sumatriptan in reducing the use of medical resources and the loss of productivity offset the price difference [84]. Cluster analysis of keywords from 2010 to 2019: 2 tension-type headache: Studies in this category included the association of multiple sclerosis with tension-type headache and migraine and the characteristics and chronicity of the two types of headache. Kister I's research [85] believes that migraine is earlier than multiple sclerosis, which may be one of the risk factors for multiple sclerosis, and it may also be its early clinical manifestations. Ashina S' study [86] argues that the chronicity of primary headache involves various risk factors. Combining these risk factors with some of the clinical features of the two types of headaches can predict the cause of the increased frequency and chronicity of primary headaches. 3 transient global amnesia: This category analyzes the relationship between migraine and transient global amnesia through a cohort study.
The results of the study show that migraine patients are at increased risk of transient global amnesia, especially women aged 40-60 [87], which provided a valuable method for the association between migraine and other diseases. 5 migraine education: This category mainly recommends the impact of migraine primary care education program on headache and the bene ts of quality of life. The research results exhibit that Mercy Migraine Management Program has a signi cant effect in improving headache frequency, cognitive and emotional aspects of headache treatment, which offers in-depth research power for migraine prevention and health care [88]. 7 laser-evoked potential: The research that was absorbed in this category is laser evoked potential. In de Tommaso M's research [89], high-frequency repetitive transcranial magnetic stimulation was utilized to detect the effect of the left primary motor cortex on subjective pain and evoked response induced by laser stimulation in contralateral hand and supraorbital region of patients with migraine without aura in a critical period. The results demonstrate that high frequency repetitive transcranial magnetic stimulation of the motor cortex has a better effect on injury than other pain regulation methods, and its potential advantages should not be ignored. 8 anxiety symptom: The focus of research in this category is that migraine recurrence is not related to depression or anxiety. Through a multicenter randomized double-blind trial study, Mitsikostas DD [90] found that the recurrence of migraine was not affected by the Hamilton Depression Scale or Anxiety Score, SCL-90-R score or treatment, indicating that depression or anxiety symptoms did not affect the recurrence of migraine in the drug treatment of acute migraine.

Comparison of research hotspots
Comparison of keyword research hotspots in the two periods: The research hotspot during 2000-2009 was "stimulation", which mainly included transcranial magnetic stimulation [91], vagus nerve stimulation [92], visual stimulation [93], light stimulation [94], laser pain stimulation [95], etc. The main effects of these stimulations are focused on the treatment of migraine, treatments such as vagus nerve stimulation for refractory migraine, occipital nerve stimulation for chronic migraine, and transcranial magnetic stimulation (including single pulse and double pulse forms) for migraine, all of which enrich the treatment of migraine. Moreover, the research hotspot in 2010-2019 is "triptan"(Most of them start from the treatment of migraine [96]), including the rst and second-generation triptans. Speci c drugs include sumatriptan, zolmitriptan, rizatriptan, naratriptan, eletriptan, uvatriptan, etc. The incidence of side effects And the severity is lower than traditional anti-migraine drugs. These studies provide evidence for the clinically reasonable and safe use of paroxysmal migraine.

Conclusions
In this paper, we used Citespace to conduct bibliometric analysis on migraine in the  Network of countries/territories on migraine The purple node in the middle of the annual ring means the in uence and the signi cance of a country/territory. The larger the node and the more purple it exhibits, the greater is the importance of the country/territory.