Increased prevalence of migraine in women with inflammatory bowel disease: A cross-sectional study

Abstract

Background

Some studies have suggested an association between migraine and inflammatory bowel disease. We determined migraine prevalence in a cohort of patients with inflammatory bowel disease.

Methods

Patients with inflammatory bowel disease aged 18–65 years were interviewed using an ad hoc headache questionnaire. Those who admitted a history of headache in the last year answered the three questions of the ID-Migraine questionnaire. Those who answered “yes” to the three of them were classified as “definite” and those who answered “yes” to two were classified as “probable” migraine.

Results

We interviewed 283 patients with inflammatory bowel disease. Of these, 176 (62.2%) had headache. Fifty-nine (20.8%; 95% CI 16.3–26.0%) met migraine criteria either definite (n = 33; 11.7%; 95% CI 8.2–16.0%) or probable (n = 26; 9.2%; 95% CI 6.1–13.2). When divided by gender, 12 men (9.6%; 95% CI 5.1–16.2%) and 47 women (29.8%; 95% CI 22.8–37.5%) met migraine criteria. The prevalence of migraine was increased in inflammatory bowel disease patients from the current cohort (20.8%) versus that reported for our general population for the same age group (12.6%; p < 0.0001). These differences remained significant in female inflammatory bowel disease patients (29.8% versus 17.2% in our general population; p < 0.0001), but not in males (9.6% in inflammatory bowel disease vs 8.0%; p = 0.30). Seventeen patients with inflammatory bowel disease (6.0%; 95% CI 3.54–9.44%) fulfilled chronic migraine criteria. There were no differences in migraine prevalence by inflammatory bowel disease subtypes.

Conclusion

Migraine prevalence, including chronic migraine, seems to be increased in patients with inflammatory bowel disease. The fact that this association was stronger for women suggests an influence of sex-related factors.

Keywords

Inflammatory bowel disease migraine prevalence

Introduction

Migraine is often disabling by itself but also due to the co-occurrence of other chronic diseases both neuropsychiatric, including anxiety-depression, insomnia, epilepsy or stroke, and non-neuropsychiatric, such as heart disease or asthma/allergies (1). Gastrointestinal symptoms (nausea/vomiting, gastroparesis) are classical hallmarks of migraine and some gastrointestinal disorders, such as irritable bowel syndrome or celiac disease, are more frequent in migraineurs as compared to the general population (2,3).

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC), Crohn’s disease (CD) and undetermined-IBD (U-IBD) is a lifetime, chronic inflammatory disorder, with some epidemiological characteristics similar to those of migraine as it is more likely to be diagnosed in children or young adults and to co-occur with other chronic conditions including depression and anxiety, asthma and some neurological disorders (4,5). Several studies have analyzed a possible comorbidity between migraine and IBD with very heterogeneous results (Table 1). Four studies, mostly coming from big insurance data-bases with incredibly low migraine prevalence, have found no association (6 –9). The remaining seven (10 –16) did find a numerical difference, but these differences were only significant in three of them (12 –14). These three positive studies cannot be interpreted as definitive as either just used one question to diagnose migraine (14), the number of included cases was too low (n = 80) (12) or the percentages found for prevalence of migraine in IBD patients and controls (41% and 21.3%, respectively) were too high (13). Our aim, therefore, was to assess, by means of a validated questionnaire with high sensitivity and specificity also in Spanish language (17,18), a possible coexistence between migraine and IBD in a series of unselected, consecutive patients attending our IBD clinic.

Table 1.

Main results of surveys analyzing migraine prevalence in IBD.

Author, year	N of IBD patients included	IBD diagnosis	Migraine diagnosis	Migraine prevalence, %	Migraine prevalence in controls, %
Ford et al., 2009	100	IBD clinic	ID-Migraine	30	Not available
Dimitrova et al., 2013	111	IBD clinic Health Survey	ID-Migraine	14	7
Anadol Kelleci et al., 2016	51*	IBD clinic	IHS-based questionnaire	17.6	17.6 (NS)
Cheraghi et al., 2016	80	IBD clinic	IHS-based questionnaire	21.3	8.8
Moisset et al., 2017	203	IBD clinic	IHS-based questionnaire	41	21.3
Bähler et al., 2017	4791	Insurance records	Insurance records	2.2	1.1 (NS)
Welander et al., 2021	4041UK	Biobank Health Survey	UK Biobank	2.9	2.98 (NS)
Leitäo et al., 2021	155	IBD clinic UK biobank	IHS-base interview	34.2	20.8 (NS)
Liu et al., 2021	862	US National Health Survey	One question**	28.1	15.2
Kim et al., 2022	1027	Insurance records	IHS questionnarie	1.6	1.1 (NS)
González-Martínez et al., 2023	66	IBD clinic	MS-Q questionnaire***	34.2%	20.8% (NS)

All reports appearing in Pubmed journals and studying migraine prevalence in IBD patients are included here (search terms: Crohn’s disease/inflammatory bowel disease/ulcerative colitis AND migraine). *This study included only patients with Crohn’s disease. **Patients were just asked “if they had migraine or severe headache”. ***Migraine screening questionnaire. NS: non-significant. Significant prevalence numbers appear in bold.

Patients and methods

Study population and design

We performed this cross-sectional study, between 21 November 2022 and 22 February 2023. To be included in this survey, IBD patients had to be between 18 and 65 years and have been diagnosed with IBD in our IBD Unit according to the Montreal Classification (19). After providing informed consent, consecutive patients with a confirmed diagnosis of IBD attending our Unit were interviewed using an ad hoc headache questionnaire (Table 2). Detailed clinical data were available for all the participants. The study received IRB approval by the Ethics Committee of Cantabria (2023/004).

Table 2.

Headache questionnaire used in this study.*

1. Did you suffer from headache last year unrelated to head injury, hangover or viral illness, such as flu or COVID-19?

2. Did you experience headache in the last three months?

3. If you had headache in the last three months, please point out the average number of days with headache:<15 days/month □ >15 days/month □

4. Has a headache limited your activities for a day or more in the last three months?

5. Are you nauseated or sick to your stomach when you have a headache?

6. Does light bother you when you have a headache?

7. Have you ever been diagnosed with migraine?

*Questions 4–6 are the ID-Migraine screening questionnaire (17,18).

IBD patients with a history of headache in the last year unrelated to head injury, hangover or a viral illness such as flu or COVID-19 were asked to answer the three questions of the ID-Migraine validated questionnaire (17). Those who answered “yes” to the three questions were classified as “definite” migraine and those who answered “yes” to two questions were classified as “probable” migraine. In these migraine patients, we also collected the subjective average frequency of headache days in the previous three months (more or less than 15 days a month). If participants had 15 or more headache days and a definite or probable migraine according to the questionnaire, they were defined as having chronic migraine. For all patients we collected demographic data, IBD diagnostic subtype, disease duration, hospitalizations, surgeries and medical treatments due to IBD.

Endpoints

The primary endpoint was to determine the prevalence of migraine in a cohort of unselected IBD patients versus that reported in our general population (20). The secondary endpoints were to analyze the prevalence of migraine in IBD patients according to sex, IBD diagnostic subtype and severity and treatment of the IBD.

Statistical analysis

Based on a reported migraine prevalence of 12.6% for our local population at 18–65 years of age (20) and an average prevalence of migraine in patients with IBD of 19% described in a recently published meta-analysis (21) we calculated that with alpha equal to 0.05 and a power of 80%, we had to include a minimum of 235 individuals.

Data are expressed as percentages with 95% confidence intervals (95% CI) calculated using the Clopper-Pearson method unless stated differently in text. Comparisons of prevalence between our IBD patients and the general population were performed using the binomial test, inferring the hypothesized values from the reported local migraine prevalence data at 18–65 years of age (20). Comparisons of proportions found in our IBD sub-groups were carried out using Fischer’s exact test.

Results

We interviewed a total of 283 consecutive IBD patients aged 18–65 years . There were 158 (55.8%) women with a mean age of 48.3 years (median 48.5 years, range 22–65 years) and 125 men (median 49 years, range 20–65 years). A total of 140 (49.1%; mean age 49.2, median 50, range 22–65 years) patients met UC criteria, 131 (46.7%; mean age 46, median 47, range 20–65 years) had CD and the remaining 12 (4.2%; mean age 46.2, median 47, range 27–62 years) were diagnosed as U-IBD. Main characteristics of this population are described in Table 3.

Table 3.

Main characteristics of total IBD population, and stratified by headache/no headache.

	Total IBD population283	No headache, total107	Headache, total176
Age years
- Mean ± SD	47.9 ± 11.8	48.9 ± 12.7	47.3 ± 11.3
- Median (range)	49 (20–65)	51 (20–65)	48 (20–65)
Sex, female (%)	158 (55.8)	48 (44.9)	110 (62.5)
IBD subtypes (%)
- UC	140 (49.1)	56 (53.8)	84 (47.7)
- CD	131 (46.7)	47 (43.9)	84 (47.7)
- U-IBD	12 (4.2)	4 (3.7)	8 (4.5)
Years since diagnosis of IBD
- Mean ± SD	9.9 ± 9.2	9 ± 9.3	10.4 ± 9.07
- Median (range)	8 (0–36)	5 (0–36)	9 (0–36)
Perianal disease (%)	27 (9.5)	6 (5.6)	21 (11.9)
Immunomodulator treatment (%)	119 (42)	39 (36.4)	80 (45.4)
Biologic treatment (%)	96 (33.9)	38 (35.5)	58 (32.9)
Surgery (%)	53 (18.7)	18 (16.8)	35 (19.9)
Hospitalizations related to IBD (%)	101 (35.7)	39 (36.4)	62 (35.2)
Immune related diseases or extraintestinal manifestations (%)	44 (15.6)	13 (12.1)	31 (17.6)

SD: standard deviation, IBD: inflammatory bowel disease, UC: ulcerative colitis, CD: Crohn’s disease, U-IBD undefined inflammatory bowel disease.

A total of 176 (62.2%) admitted a history of headache unrelated to head injury, hangover or a viral illness. Of those, 59 (20.85%; 95% CI 16.26–26.05%) IBD patients met migraine criteria either definite (n = 33; 11.66%; 95% CI 8.16–15.99%) or probable (n = 26; 9.18%; 95% CI 6.09–13.17) (Figure 1). When divided by gender, 12 men (prevalence 9.6%; 95% CI 5.06–16.17) and 47 women (prevalence 29.75%; 95% CI 22.75–37.53%) met migraine criteria. There were 17 IBD patients (6.0%; 95% CI 3.54–9.44%) who met chronic migraine criteria (11 women, eight definite and three probable migraine; prevalence 7% and six men, three probable and three definite; prevalence 4.7%) (Table 4).

Figure 1.

Flow chart of IBD patient selection and distribution.

Table 4.

Main characteristics of IBD population, stratified by headache without migraine, total migraine, probable migraine and definite migraine.

	Headache without migrainen = 117	Total migrainen = 59	Probable migrainen = 26	Definite migrainen = 33
Age years
- Mean ± SD	47.2 ± 11.5	47.25 ± 11.1	46 ± 10.6	48.2 ± 11.6
- Median (range)	48 (22–65)	46 (20–65)	46 (20–61)	48 (23–65
Sex, female (%)	63 (53.8)	47 (79.7)	20 (76.9)	27 (81.8)
IBD subtypes (%)
- UC	55 (47.0)	29 (49.2)	14 (53.8)	15 (45.5)
- CD	58 (49.6)	26 (44.1)	10 (38.5)	16 (48.5)
- U-IBD	4 (3.4)	4 (6.8)	2 (7.7)	2 (6.1)
Years since diagnosis of IBD
- Mean ± SD	10.7 ± 9.5	9.9 ± 8.2	9.6 ± 8.4	10.2 ± 8.2
- Median (range)	9 (0–36)	8 (0–33)	8 (1–33)	10 (0–36)
Perianal disease (%)	14 (12.0)	7 (11.9)	5 (19.2)	2 (6.1)
Immunomodulator treatment (%)	56 (47.9)	24 (40.7)	9 (34.6)	15 (45.5)
Biologic treatment (%)	40 (34.2)	18 (30.5)	8 (30.8)	10 (30.3)
Surgery (%)	25 (21.4)	10 (16.9)	5 (19.2)	5 (15.1)
Hospitalization (%)	40 (34.2)	21 (35.6)	10 (38.5)	11 (33.3)
Immune related diseases or extraintestinal manifestations (%)	15 (12.8)	16 (27.1)	7 (26.9)	9 (27.3)
>15 days of migraine/month		17 (28.8)	6 (23.1)	11 (33.3)

SD: standard deviation, IBD: inflammatory bowel disease, UC: ulcerative colitis, CD: Crohn’s disease, U-IBD undefined inflammatory bowel disease.

We compared these prevalence data with those reported on migraine prevalence in our country in the same age group (20). The prevalence of migraine was significantly increased in IBD patients versus that reported for our general population (12.56%; 95% CI 11.6–13.6%; p < 0.0001). The prevalences of definite and probable migraine are also increased in IBD (p < 0.05 and p < 0.001, respectively) when compared with the general population (definite: 8.40%; 95% CI 7.69–9.15%; probable:4.16%; 95% CI 3.7–4.7%). Stratified by sex, differences in total migraine prevalence remained significant in women (general population: 17.17%; 95% CI 15.82–18.61%; p < 0.0001), but not in men (general population: 8.04%; 95% CI 7.10–9–10%; p = 0.30) (Figure 2).

Figure 2.

Migraine prevalence in our IBD patients versus the general population. Notice that prevalence of total, probable and definite migraine in IBD patients was significantly higher than those of the general population, but only for females. General population data taken from reference 20. ns: non-significant; *p < 0.05; **p < 0.01: ***p < 0.001; **** p < 0.0001.

By IBD diagnostic subtypes, 29 (20.7%; 95% CI 14.33–28.38%; 14 probable and 15 definite) of UC, 26 (19.8%; 95% CI 13.39–27.71%; 10 probable and 16 definite) of CD and four (33.3%; 95% CI 6.81–49.90%; two probable and two definitive) of U-IBD patients met migraine diagnostic criteria. There were no significant differences in migraine prevalence between CD and UC (p = 0.88) (Figure 3).

Figure 3.

Prevalence of migraine in IBD and main IBD subtypes (UC and CD) versus our general population showing a significant, uniform increase in migraine prevalence for IBD, CD and UC. General population data taken from reference 20. ns: non-significant; ****: p < 0.0001.

Regarding IBD characteristics and migraine, men with total migraine had a higher rate of use of biologic treatment (75% vs 40.7% p < 0.05) and of immune mediated inflammatory diseases or extraintestinal manifestations of IBD (33.3% vs 9.6% p < 0.05). These associations were not significant for women, nor for the overall population (p>0.05). Additionally, we did not find any significant influence in the prevalence of migraine with/without the use of mesalazine or immunomodulators, previous surgeries or hospitalizations due to IBD, neither in total number of patients nor stratified by sex.

Discussion

The main finding of this work is that one out of five (exactly 20.85%) among unselected patients with an established diagnosis of IBD met migraine criteria according to the validated ID-Migraine questionnaire (11.66% and 9.18% definite and probable criteria, respectively). There are two big surveys of migraine prevalence in the general population exactly at the age range of this study in our country (20,22). In both studies patients were interviewed using a structured questionnaire. The first, carried out in 1992 and involving 2232 subjects examined at home by neurologists, used the 1988 IHS migraine criteria and found that exactly 12% of the population (17% women and 8% men) in Spain had migraine (22). The most recent study involved 5668 subjects from the general population aged 18–65 years and found an almost identical 12.6% 1-year migraine prevalence (17.2% in males and 8.0% in females) (20). In this study, 8.4% and 4.2% met definite and probable migraine criteria, respectively. When compared with data coming from Matías-Guiu et al.’s survey (22), global migraine prevalence in our series of IBD patients was numerically and significantly increased. The same can be concluded comparing our results with those from a very recent meta-analysis, which has calculated that 15.2% of the population aged 20–65 years (18.6% of women and 8.7% of men) suffers from active migraine (23). As shown in Table 1, results from 11 previous reports testing this possible association are heterogenous. Although our final numbers are low to draw definitive conclusions and our study does not include a longitudinal follow-up, the proportion of our IBD patients who would meet chronic migraine criteria (6%) are also clearly higher than those reported globally (24) and specifically in our region (2%) (25), which suggests not only an association between IBD and migraine, but that the presence of IBD would predispose to migraine chronicity.

We also show that global migraine prevalence remains higher than that of the general population in, CD and UC, the two main types of IBD, a question unexamined in those studies which had found a significant association between IBD and migraine. What could be the reasons for such migraine and IBD comorbidity? By definition, IBD is a chronic (systemic) inflammatory disease (4,5) and inflammation might play a role in migraine initiation and chronification (26). Migraine has been shown to be associated with other inflammatory disorders and neurogenic inflammation, with increased expression of proinflammatory cytokines, including interleukins 1β, 6 and 8, and tumor necrosis factor alpha, has been linked to migraine pathophysiology (26). This comorbidity between migraine and IBD could be another example of the bidirectional relationship between the gastrointestinal and the central nervous system known as the “gut-brain axis”, which has been involved in the pathophysiology of migraine in other gastrointestinal disorders, such as celiac disease, irritable bowel syndrome or Helicobacter infection (27). The mechanisms of how brain and the gut interact in migraine patients are not entirely clear, but changes in the microbiota and in the biochemistry of neuronal innervation on the gastrointestinal tract could be implicated. Microbiota prevents systemic inflammation and plays a key role in nociception by preparing host adaptation to stress factors (27,28). The neuronal influence on the inflammatory status of the gastrointestinal tract is well-demonstrated involving a variety of neurotransmitters, such as serotonin, and of pain-producing neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP has been shown to exert a key role in both migraine and gut mucosa homeostasis: an excess of CGRP induces migraine pain and diarrhea (29), while lack of CGRP induces colitis and spontaneous lymphoid hyperplasia, which indicates a protective role in bowel inflammation (30).

There are other factors which could contribute to this association. The association between migraine and IBD was only significant for females, which could suggest a role for sex-linked factors, such as oestrogens (31,32) or even genetic predisposition depending on sexual chromosomes (33). On the other hand, non-steroidal anti-inflammatory agents are the most popular acute treatment of migraine and they have been shown to have the potential to trigger the onset or relapse of IBD (34).

Even though all patients with IBD — regardless of their clinical situation — are followed in our IBD Clinic, one limitation of our study is that it was conducted in a specialized clinic in a tertiary-care center and, therefore, their results are not necessarily transposed to the generality of IBD subjects. Although our study contains the highest number of subjects tested in this regard in a specialized IBD clinic (see Table 1), it is true that we should be cautious on interpreting results coming from subgroups with a final low number of subjects, such as males or chronic migraineurs, as definitive. In spite of its high sensitivity (0.92) and specificity (0.82) for migraine diagnosis (18), ID-Migraine questionnaire is a screening tool rather than a diagnosis made by an expert physician. Finally, one further limitation is that there was no simultaneous, matched control group from the general population to compare migraine prevalence, but we think that the very consistent results from the two big prevalence studies in our country (and those of the recent metanalysis of migraine prevalence in Europe) make a fair comparison possible.

Conclusions

This cross-sectional study supports previous surveys reporting an association between IBD and migraine. The fact that this association was stronger for women suggests an influence of sex-related factors.

Article highlights

IBD and migraine are comorbid diseases; the presence of IBD could contribute to migraine chronicity.

This comorbidity was significant only for women, which suggests an influence of sex-related factors.

Footnotes

Acknowledgments

We are very grateful to our IBD nurse María Soledad Serrano for her continuous support.

Declarations of conflicting interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study has been founded by Instituto de Salud Carlos III (ISCII) through the project PI20/01358 and co-funded by Fondos Europeos de Desarrollo Regional (FEDER), “Una manera de hacer Europa”.

ORCID iD

Julio Pascual

References

Buse

Reed

Fanning

, et al. Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study. J Headache Pain 2020; 21: 23.

Cole

Rothman

Cabrla

, et al. Migraine, fibromyalgia, and depression among people wity IBS: a prevalence study. BMC Gastroenterol 2006; 6: 26.

van Hemert

Bredveld

Rovers

JMP

, et al. Migraine associated with gastrointestinal disorders: review of the literature and clinical implications. Front Neurol 2014; 5: 241.

Ungaro

Mehandru

Allen

, et al. Ulcerative colitis. Lancet 2017; 389: 1756–1770.

Torres

Mehandru

Colombel

, et al. Crohn’ disease. Lancet 2017; 389: 1741–1755.

Anadol Kelleci

Calhan

Sahin

, et al. The prevalence of headache in Crohn’s disease: single-center experience. Gastroenterol Res Pract 2016: 6474651.

Bähler

Schoepfer

Vavricka

, et al. Chronic comorbidities associated with inflammatory bowel disease: prevalence and impact on healthcare costs in Switzerland. Eur J Gastroenterol Hepatol 2017; 29: 916–925.

Welander

Olivo

Pisanu

, et al. Migraine and gastrointestinal disorders in middle and old age: A UK biobank. Brain Behav 2021; 11: e2291.

Kim

Lee

Rhew

Association between gastrointestinal diseases and migraine. Int J Environ Res Public Health 2022; 19: 4018.

10.

Ford

Finket

Isaacs

KI.

Migraine in patients with inflammatory bowel disorders. J Clin Gastroenterol 2009; 43: 499.

11.

Dimitrova

Ungaro

Lebwohl

, et al. Prevalence of migraine in patients with celiac disease and inflammatory bowel disease. Headache 2013; 53: 344–355.

12.

Cheraghi

Daryani

Ghabaee

A survey of migraine prevalence in patients with inflammatory bowel disease-a single centre experience. Middle East J Dig Dis 2016; 8: 282–288.

13.

Moisset

Bommelaer

Boube

, et al. Migraine prevalence in inflammatory bowel disease patients: a tertiary-care centre cross-sectional study. Eur J Pain 2017; 21: 1550–1560.

14.

Liu

Wheaton

, et al. The association between inflammatory bowel disease and migraine or severe headache among US adults: Findings from the National Health Interview Survey, 2015-2016. Headache 2021; 61: 612–616.

15.

Leitäo

AMF

Ribeiro Junio

Araújo

, et al. Neuropathy and primary headaches affect different subgroups of inflammatory bowel disease patients. Neurol Sci 2021; 42: 935–942.

16.

González-Martínez

Muro

Quintas

, et al. Headache in patients with inflammatory bowel disease: migraine prevalence according to the Migraine Screening-Questionnaire (MS-Q) and headache characteristics. Gastroenterol Hepathol. Epub ahead of print 2023 May 5.

17.

Lipton

Dodick

Sadovsky

, et al. A self-administered screener for migraine in primary care. The ID Migraine^TM validation study. Neurology 2003; 61: 375–382.

18.

Rodríguez-Rivas

Moreno-Martínez

Translation and validation to Spanish of the diagnostic test ID-Migraine. Neurology 2022; 98: 98.

19.

Silverberg

Satsangi

Ahmad

, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005; 19: 5A–36A.

20.

Matías-Guiu

Porta-Etessam

Mateos

, et al. One-year prevalence of migraine in Spain: a nationwide population-based survey. Cephalalgia 2011; 31: 463–470.

21.

Olfati

Mirmosayyeb

Hosseinabadi

, et al. The prevalence of migraine in inflammatory bowel disease, a systematic review and meta-analysis. Int J Prev Med 2023; 14: 66.

22.

Laínez

MJA

Vioque

Hernández-Aguado

, et al. Prevalence of migraine in Spain. An assessment of the questionnaire’s valididty by clinical interview. In: Olesen

(ed.) Headache Classification and Epidemiology. New York: Raven Press, 1994, pp. 221–225.

23.

Stovner

Hagen

Linde

, et al. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain 2022; 23: 34.

24.

Natoli

Manack

Dean

, et al. Global prevalence of chronic migraine: a systematic review. Cephalalgia 2010; 30: 599–609.

25.

Castillo

Muñoz

Guitera

, et al. Kaplan Award 1998. Epdemiology of chronic daily headache in the general population. Headache 1999; 39: 190–196.

26.

Edvinsson

Haanes

Warfvinge

Does inflammation have a role in migraine?

Nat Rev Neurol 2019; 15: 483–490.

27.

Arzani

Jahromi

Ghorbani

, et al. Gut-brain axis and migraine headache: a comprehensive review. J Headache Pain 2020; 21: 15.

28.

Wang

Xiong

, et al. A causal effects of gut microbiota in the development of migraine. J Headache Pain 2023; 24: 90.

29.

Falkenberg

Bjerg

Olesen

Two-hour infusion causes gastrointestinal hyperactivity: possible relevance for CGRP antibody treatment. Headache 2020; 60: 929–937.

30.

Thompson

Washington

Kurre

, et al. Protective roles of alpha-calcitonin and beta-calcitonin gene-related peptide in spontaneous and experimentally induced colitis. Dig Dis Sci 2008; 53: 229–241.

31.

Jacenik

Cygankiewicz

Mokrowiecka

, et al. Sex- and age-related estrogen signalling alteration in inflammatory bowel diseases: modulatory role of estrogen receptors. Int J Mol Sci 2019; 20: 3175.

32.

van der Giessen

van der Woude

Peppelenbosch

, et al. A direct effect of sex hormones on epithelial barrier function in inflammatory bowel disease models. Cells 2019; 8: 261.

33.

Lee

Yang

, et al. X chromosome-wide association study identifies a susceptibility locus for inflammatory bowel disease in Koreans. J Crohn’s Colitis 2017; 11: 820–830.

34.

Habib

Mazulis

Roginsky

, et al. Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: pathophysiology and clinical associations. Inflamm Bowel Dis 2017; 20: 2493–2502