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Abstract There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary head-aches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the litera-ture to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disor-ders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disor-ders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disor-ders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are im-proved or cured along with the treatment of the gastrointestinal disorder. Key words: Headache; migraine disorders; gastrointestinal diseases; medicine, traditional; headache disorders, primary; headache disorders, secondary
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Emergency (2016); 4 (4): 171-183
REVIEW ARTICLE
Gastrointestinal Headache; a Narrative Review
Majid T Noghani1, Hossein Rezaeizadeh2, Sayed Mohammad Baqer Fazljoo3, Mansoor Keshavarz2,4*
1. Department of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran.
2. School of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran.
3. School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
4. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
*Corresponding author: Mansoor Keshavarz; Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Email: mkeshavarz@tums.ac.ir; Tel/Fax: +9821-66 419484.
Received: July 2015; Accepted: September 2015
Abstract
There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report
resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are
classified by The International Headache Society as primary or secondary; however, among the secondary head-
aches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the litera-
ture to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disor-
ders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease
(GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disor-
ders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission
or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses
explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin
pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian
physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disor-
ders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest
providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are im-
proved or cured along with the treatment of the gastrointestinal disorder.
Keywords: Headache; migraine disorders; gastrointestinal diseases; medicine, traditional; headache disorders,
primary; headache disorders, secondary
Cite this article as: Noghani MT, Rezaeizadeh H, Fazljoo SMB, Keshavarz M. Gastrointestinal headache; a narrative review. Emer-
gency. 2016;4(4):171-183
Introduction:
eadache is one of the common reasons for daily
visits to emergency departments (ED). Sadly, in
some cases despite all the diagnostic and treat-
ment measures, the cause of the headache cannot be de-
termined and only symptoms are treated. In these cases,
the patient experiences decreased quality of life and re-
lapse, and therefore frequently revisits ED and neuro-
logic clinics. The international headache society (IHS) re-
leased the second edition of the international classifica-
tion of headache disorders (the ICHD-II) in 2004, and the
ICHD-III (beta version) recently, with which various
headache disorders are diagnosed by physicians
throughout the globe. Primary headaches, which are not
considered to be attributed to another disorder are
partly found to be cured or relieved by management of
gastrointestinal (GI) abnormalities in the affected pa-
tients (1, 2). In the initial evaluations, some probable
causes of headaches, such as GI disorders, are over-
looked. Providing evidence for primary headaches asso-
ciated with GI disorders, may help classify this type of
headache as a unique diagnostic entity. Ancient Persian
physicians believed in a type of headache arising from
disorders of the stomach and as an individual entity, de-
scribed it in their writings as participatory headache of
gastric origin or simply, “Gastric Headache” (3). We
therefore, performed a review of the available literature
to show the extent of the studies demonstrating the
prevalence of headache and GI disorders’ coexistence, as
well as studies proposing GI abnormalities as etiologies
for headaches in which, treatments targeting the GI dys-
function relieved the headache.
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Noghani et al
172
Methods:
Review of the available literature from 1980 to July
2014, through a PubMed search was provided. Searching
the MeSH terms “Gastrointestinal Diseases” or “Migraine
Disorders” or “Headache Disorders” by the PubMed
search builder altogether revealed roughly 900 articles.
Abstracts from pertinent articles were obtained. There
were no language restrictions. If the study pointed to the
association of any headache disorder with GI dysfunc-
tions the paper was completely studied. In addition,
bibilography and citations to the selected studies were
evaluated and relevant articles not found previously
were also included in order to augment the search re-
sults. In addition, a MEDLINE search was conducted us-
ing the keywords “Iranian Traditional Medicine”, “Per-
sian Medicine”, and “Islamic Medicine” and relevant pa-
pers were extracted. Finally, principle texts of Tradi-
tional Persian Medicine and the highly credited manu-
scripts on the subject of headache were studied.
Results:
- Dyspepsia
Dyspepsia, defined as postprandial fullness, early sa-
tiety, or epigastric pain or burning by the Rome Commit-
tee, is reported to be present in a significant number of
patients suffering from migraine (Table 1). Kurth et al.
studied a population of migraineurs and compared them
with a group of controls using a bowel disease question-
naire and reported pain centered in the upper abdomen
to be significantly more frequent among patients with
migraine (4). In another case-control study conducted by
Meucci et al. among dyspeptic patients, it was noted that
this group of patients suffer significantly from migraine
compared to the control group. It was suggested that
dyspeptic patients of the dismotility-like or with nausea
/ vomiting referred for endoscopy be worked up for a di-
agnosis of migraine. Given the completely normal endo-
scopic appearance seen in 90% of the migraineurs it was
concluded that dyspeptic symptoms may be a conse-
quence of the migraine (5). Mavromichalis et al. how-
ever, demonstrated underlying inflammatory lesion in
29 of the 31 migraineurs undergoing endoscopy, sup-
porting a causal link between GI inflammation and mi-
graine. Treatment targeting the GI tract resulted in relief
of migraine (6).
Since the former two studies were not interventional,
one could not conclude whether treatment of dyspepsia
would have attenuated migraine headaches. However,
Sung Hwang et al. demonstrated the resolution of head-
ache in a group of children with epigastric pain or ten-
derness diagnosed with primary headache after initiat-
ing regular anti-acid medication (7). Spierings reported
a 50 year old dyspeptic male complaining of headache
since early adulthood. Patient`s dyspeptic symptoms
were treated by Cisapride 20 mg daily before dinner and
subsequently the headache was almost completely re-
solved (2). Interventional studies are needed to provide
more evidence to support the concept that in at least
some migraineurs, their dyspeptic symptoms are the
cause of their headaches.
- Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD), described as
abnormal reflux of gastric contents into the esophagus
resulting in symptoms or mucosal damage, may manifest
with typical and atypical symptoms (8). However, among
the extra-esophageal symptoms, headache is not pro-
nounced as other atypical symptoms are. There is a
growing body of literature demonstrating the associa-
tion of headache with reflux symptoms (Table 1).
Aamodt et al. performed the Head-HUNT study involving
more than 43,000 individuals and reported reflux symp-
toms to be the most common symptom in this population
with a rough prevalence of 30%. Headache was noted to
have a higher prevalence among individuals with much
reflux symptoms compared to those without such com-
plaints. In this study, patients suffering from headache
were classified into migrainous and non-migrainous (9).
In another study, Katic et al. aimed to determine the
prevalence of GERD and heartburn in a group of more
than 1800 migraine patients. Almost half of the mi-
graineurs were reported to have GERD, heartburn, or re-
lated symptoms and this group suffered from more se-
vere migraines and greater frequency of attacks (10).
A population based study, enrolling close to 2000 indi-
viduals, reported significant correlation between head-
ache and symptoms associated with GERD. It was noted
that some patients’ headaches intensified with increased
heartburn, and therefore, headaches were assumed to be
a complication of GERD. The types of headaches, how-
ever, were not classified in this study (11).
Spierings reported two patients with headaches associ-
ated with reflux, in whom proton pump inhibitors re-
solved their headaches (1). Further interventional stud-
ies targeting acid reflux suppression in patients affected
by both disorders may be of benefit for understanding
the causal relationship.
- Constipation
Constipation is well known as a factor precipitating en-
cephalopathy in patients with advanced liver disease.
The mechanism involves retention of waste materials in
the gut and reabsorption of toxic elements namely am-
monia through blood circulation, reaching the brain and
causing central nervous system (CNS) dysfunction (12).
However, when hepatic function is not compromised,
the ammonia is cleared out of the circulation and there-
fore, constipation is not considered to cause any signifi-
cant disturbance. On the other hand, there is evidence
that constipation may be associated with headache, rais-
ing the question about the impact of constipation on CNS
even in the absence of advanced liver disease.
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173
Emergency (2016); 4 (4): 171-183
Table 1: Gastrointestinal disorders reported to be associated with headache including migraine
Study
Year
Country
Sample
size
Age
group
Gender
(female)
Findings
Dyspepsia
Mavromichalis et
al. (13)
1997
Greece
31
Children
58.1%
There is causal link between recurrent abdominal pain and
migraine.
Spierings* (1)
2002
USA
2
Adult
100%
The dyspepsia triggered headaches.
Meucci et al. (5)
2005
Italy
698
Adult
39.2%
Migraine is associated with dysmotility-like dyspepsia.
Pucci et al. (14)
2005
Italy
14
Adult
85.7%
There is causal link between recurrent abdominal pain and
migraine.
Aurora et al. (15)
2006
Sweden
20
Adult
75%
Migraines patients suffer from gastric stasis both during and
outside an acute migraine attack.
Kurth et al. (4)
2006
Germany
587
Adult
46.5%
Upper abdominal symptoms are significantly more frequent in
patients with migraine compared with healthy controls
Hwang et al.*(7)
2008
Korea
58
Children
70%
The study supports any specific correlation between headache
and epigastric pain or tenderness
Modiri et al. (16)
2012
USA
84
Adult
82.1%
Headaches, especially migraines, are present in two-thirds of
patients with gastroparesis.
Reflux symptoms
Spierings* (1)
2002
USA
2
Adult
100%
The reflux triggered headaches and responded to specific re-
flux treatment.
Aamodt et al. (9)
2008
Norway
43,782
Adult/
Children
63.3%
The finding may suggest that headache sufferers generally are
predisposed to reflux.
Saberi-Firoozi et al.
(11)
2007
Iran
1,956
Adult
64.8%
gastroesophageal reflux disease is associated with headache.
Katic et al. (10)
2009
USA
1,832
Adult
73%
22.0% OF migraineurs reported having diagnosed GERD and
15.8% reported reflux symptoms.
Constipation
Aamodt et al. (9)
2008
Norway
43,782
Adult/
Children
63.3%
The finding showed prevalence of the migraine was higher in
constipate patients.
Inaloo et al. (17)
2014
Iran
326
Children
48.2%
The study showed a strong correlation between headache and
chronic functional constipation
Park et al. (18)
2015
Korea
168
Children
52.1%
Resolution of constipation improves headache in many pa-
tients diagnosed with primary headache
*, Studies in which headache was reported to improve or resolve following management of the GI disorder.
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174
Table 1: Continue…
Study
Year
Country
Sample
size
Age
group
Gender
(female)
Findings
Abdominal pain
Anttila et al.
(19)
2001
Finland
513
Children
49.9%
Children with migraine and nonmigrainous headaches report higher
frequencies of abdominal pain.
Groholt et al.
(20)
2003
Nordic
countries
6,230
Children
46.7%
There was an association between the abdominal pain and incidence
of headache.
Boccia et al.
(21)
2006
Italy
60
Children
58%
Most children with migraine report FGIDs, associated with a delayed
gastric emptying
Walker et al.
(22)
2010
USA
200
Young
adult
62%
Children with abdominal pain that persists into adulthood may be at
increased risk for headache.
Dengler-Crish
et al. (23)
2011
USA
249
Children
67.9%
Children with functional abdominal pain may identify a group that is
at risk for headache later in life.
Chelimsky et
al. (24)
2012
USA
38
Children
63.2%
40% of functional gastrointestinal disorders patients had migraine.
Inflammatory bowel syndrome
Vandvik et al.
(25)
2004
Norway
208
Adult
67%
44.7% of patients with irritable bowel syndrome suffer from head-
ache or migraine.
Hershfield et
al. (26)
2005
Canada
200
Adult
64.5%
47% of patients with irritable bowel syndrome Have headache.
Agrawal et al.
(27)
2009
UK
211
Old adult
65.2%
50% of patients with irritable bowel syndrome suffer from headache.
Park et al. (28)
2013
Korea
109
Adult
87.2
40.4% of migraine patients have irritable bowel syndrome.
Inflammatory bowel disorders
Hershfield et
al. (26)
2005
Canada
200
Adult
66.5%
19% of patients with irritable bowel syndrome suffer from headache.
Oliviera et al.
(29)
2008
Brazil
82
Adult
51.2%
Neurological disorders, such as headache, are common in inflamma-
tory bowel disease patients
Ford et al.
(30)
2009
USA
100
Adult
77%
The prevalence of migraine in the inflammatory bowel disease sam-
ple was 30%. Migraine was more prevalent in the CD subjects (36%)
than UC subjects (14.8%)
Dimitrova et
al. (31)
2013
USA
502
Adult
67.3%
Migraine was more prevalent in celiac disease and inflammatory
bowel disease subjects than in controls.
*, Studies in which headache was reported to improve or resolve following management of the GI disorder.
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175
Emergency (2016); 4 (4): 171-183
Table 1: Continue…
Study
Year
Country
Sample
size
Age
group
Gender
(female)
Findings
Celiac disease
Serratrice et
al.*(32)
1998
France
1
Adult
100%
Treatment of coeliac disease coincided with total disappearance of
severe migraine attacks.
Spina et al.*
(33)
2000
Italy
1
Children
100%
Treatment with three months of gluten free diet, it was obtained the
complete resolution of the headache.
Roche-Herrero
et al. (34)
2000
Spain
86
Children
NR
An increased prevalence of both migraine and tension headaches was
observed in the coeliac patients.
Gabrielli et al.*
(35)
2003
Italy
236
Adult
70%
During the 6 months of gluten free diet, one of the four patients had
no migraine attacks, and the remaining three patients experienced an
improvement in frequency.
Alehan et al.
(36)
2008
Turkey
200
Children
56.2%
There was an association between migraine and celiac disease.
Lionetti et al.*
(37)
2009
Italy
554
Children
67.5%
The researchers reported a high frequency of headaches in patients
with celiac diseases.
Francavilla et
al. (38)
2014
Italy
15
Children
33.3%
20% of patients with celiac disease suffer from headache.
Helicobacter pylori infection
Gasbarrini et
al.* (39)
1997
Italy
225
Adult
NR
H. pylori is common in subjects with migraine. Bacterium eradication
causes a significant decrease in attacks of migraine.
Gasbarrini et
al.* (40)
1998
Italy
148
Adult
66.4%
H. pylori infection is common in primary headache; bacterium eradi-
cation appears to be related to a significant reduction in clinical at-
tacks of the disease
Tunca et al.*
(41)
2004
Turkey
120
Children
61.7%
Helicobacter pylori positiveness is more relevant in the migranous
patients compared with controls.
Yiannopoulou
et al. (42)
2007
Greece
39
Adult
75.5%
H. pylori infection is a probable independent environmental risk fac-
tor for migraine without aura.
Hong et al.*
(43)
2007
China
50
Adult
42%
Intensity, duration, and frequency of attacks of migraine were re-
duced after H. pylori eradication.
Hosseinzadeh
et al. (44)
2011
Iran
140
Adults
76.5%
Active H. pylori infection is strongly related to the outbreak and se-
verity of migraine headaches.
Faraji et al.*
(45)
2012
Iran
64
Adult
73.4%
H. pylori eradication may have a beneficial role on management of
migraine headache.
Ansari et al.*
(46)
2015
Iran
133
Adult
NR
H. pylori eradication could be a cure or to reduce the severity and
course of migraine headaches.
*, Studies in which headache was reported to improve or resolve following management of the GI disorder. NR: Not reported.
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Noghani et al
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Spierings reported a 47 year old female patient with
chronic constipation complaining of headaches since ad-
olescence. Dietary change targeting the treatment of
constipation reduced the frequency of the headaches (2).
The Head-HUNT study further demonstrated this associ-
ation and reported a higher prevalence of headache
among individuals with much constipation compared
with those without such a complaint (9).
This suggests constipation to be considered in the con-
text of and as a triggering factor for headaches including
migraine.
- Abdominal pain & inflammatory bowel syndrome
Headaches with migrainous features are reported in
40% of children with functional gastrointestinal disor-
ders (FGID) (24). GI symptoms occurring during mi-
graine attacks such as nausea or vomiting are well ap-
preciated, but there is a growing body of evidence, which
points to the occurrence of GI symptoms especially ab-
dominal pain, outside the bouts of headaches (Table 1).
A population-based follow-up study investigated the
comorbidity of other pains in 513 school-aged children
with primary headache and found recurrent abdominal
pain to be present in 50% of the patients (19). A large
cross sectional study involving 6230 subjects evaluated
the prevalence of recurrent complaints in various sites
among 7-17 year-old population. The most common pain
combination was reported to be headache and ab-
dominal pain (20).
Boccia et al. determined the prevalence of FGIDs in mi-
grainous children and found it to be present in 70% of
the patients, among which functional abdominal pain
(FAP) comprised 35% of all. This population also suf-
fered from prolonged total gastric emptying time. Treat-
ment with Flunarizine significantly reduced the head-
aches and GI symptoms (21). FAP in childhood is be-
lieved to persist into adulthood in nearly a third of the
cases. One study reported that among those with unre-
solved FAP, headaches are reported to be more preva-
lent compared to adults in whom childhood FAP did not
continue (22). In addition, children with FAP have been
shown to suffer more from headache and other non-GI
somatic symptoms compared to healthy controls. More
than one-third of these children go on to develop FGIDs
at follow up as adolescents and adults (23).
One of the most common FGIDs is IBS, which manifests
with abdominal pain or discomfort and changes in bowel
habits. The comorbidities of this disorder have been
widely studied and it is now evident that patients with
IBS suffer from a wide range of non-GI symptoms. One of
the most appreciated comorbid non-GI symptoms is
headache. It has been reported that 30-50% of patients
with IBS, complain of headache (Table 1) (25-28, 47, 48).
On the other hand, up to 30% of migrainous patients are
reported to suffer from IBS. These findings may be ex-
plained in two ways. Either migraine or other primary
headaches are not episodic diseases, but in fact they are
disorders with underlying abnormality involving other
systems that manifest with episodic attacks, or the head-
aches are manifestations or sequels of disorders in other
body systems namely the GI tract.
- Inflammatory bowel disorders
Migraine headaches have a higher prevalence in patients
with IBD compared to that of the general population
(30). Dimitrova studied 111 patients with IBD 23% of
which reported chronic headaches and this figure was
significantly higher than controls (OR = 2.66; 95% con-
fidence interval [CI]: 1.08-6.54) (31). In Brazil, a pro-
spective study demonstrated headache to be the most
common neurological complaint among 82 patients with
IBD, 25% of which met the migraine criteria (29). Gener-
alized inflammatory response rather than isolated bowel
inflammation may play the key role in the pathogenesis
of the extra-intestinal manifestations of IBD (49).
- Celiac disease
Also known as non-tropical sprue and gluten-sensitive
enteropathy, celiac disease (CD) is now recognized as a
multisystem autoimmune disorder characterized by in-
flammation of the small intestine caused by dietary glu-
ten and related proteins in genetically susceptible indi-
viduals (50).
After the publication of case reports introducing mi-
graine as the first manifestation of CD and complete res-
olution of symptoms following gluten free diet (32, 33),
many studies aimed at investigating the association of
primary headaches with CD in children and adults (Table
1) (34-38).
Recruiting 188 adult patients with CD and 25 with gluten
sensitivity using an ID-Migraine tool, Dimitrova reported
chronic headaches to be present in 30% of celiac patients
(OR = 3.79; 95% CI: 1.78-8.10) and 56% of patients with
non-celiac gluten sensitivity, but only in 14% of controls
(P < 0.0001) (31). Two studies involving pediatric CD pa-
tients were also conducted and similar results to adult
studies were reported. In a case control study, contrary
to the study performed previously (51), Alehan et al. in-
vestigated the presence of tissue transglutaminase IgA
antibodies in a group of pediatric migraineurs and found
it to be positive in 5.5% of the patients compared to 0.6%
of the control group and the difference was statistically
significant (36). In an interesting study, Lionetti et al. ret-
rospectively evaluated the prevalence of primary head-
ache (based on the IHS criteria) in 354 children diag-
nosed with CD. In addition, they prospectively studied
the prevalence of CD in a group of pediatric patients with
primary headache. In the retrospective phase, they re-
ported headache to be present in 25% of the patients be-
fore the diagnosis of CD, compared with eight percent of
the control group (P < 0.001). In the prospective part, CD
was diagnosed by the means of serology and biopsy in
5% of the patients compared with 0.6% of the general
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177
Emergency (2016); 4 (4): 171-183
population (P < 0.005). Headaches were relieved (and in
some completely resolved) after the institution of GFD in
patients affected by both conditions (37). Contradicting
results have been recently reported in a study, which
demonstrates the prevalence of CD in migraine children
to be the same as in healthy controls. However, they also
showed that GFD improved headaches in the group of
children found to have CD (52). Large multicentric stud-
ies may resolve these discrepancies.
- Helicobacter Pylori Infection
H. Pylori infection is associated with various extradiges-
tive diseases such as ischemic heart disease, primary
Raynaud phenomenon, primary headache, alopecia ar-
eata, and hepatic encephalopathy (53).
Gasbarrini et al. reported the association of H. Pylori in-
fection with primary headache and the improvement of
symptoms with eradication of the bacteria (39, 40). Con-
tradictory results were reported afterwards (54, 55),
however, more recent studies mainly using histological
analysis of gastric mucosa biopsy for H. Pylori detection
have favored its pathogenic role in migraine (41-44). A
double blind randomized clinical trial in 2012, reported
the beneficial effects of H. Pylori eradication in manage-
ment of migraine patients (45). Overall, regarding stud-
ies supporting a role for H. Pylori in migraine it may be
judicious to identify H. Pylori infection in migraineurs by
noninvasive means especially if suffering comorbid GI
symptoms.
Pathophysiology
The pathophysiology of headache disorders especially
migraine and various GI abnormalities are widely stud-
ied individually. However, the scientific literature about
mechanisms underlying the comorbidity of the two con-
ditions is scant. Few hypotheses exist aiming to explain
the association of headache and GI disorders.
- Central sensitization and parasympathetic re-
ferred pain:
Longstanding visceral afferent stimuli on convergent
viscera-somatic neurons result in expansion of the re-
ceptive fields in size and number, decreased response
thresholds, and amplification of response magnitude.
This process leads to hyper-responsiveness of neurons
within the CNS to nociceptive and non-nociceptive stim-
uli, which is defined as central sensitization (56).
Dyspeptic migraineurs are shown to have postprandial
hypersensitivity to gastric distention. It is postulated
that this hypersensitivity in dyspeptic patients, results
from abnormal processing of gastric stimuli at the level
of the CNS. This in turn activates the common pain net-
work for both somatic and visceral pain, therefore caus-
ing headache (14).
The “parasympathetic referred pain” theory is hypothe-
sized for explaining the comorbidity of various GI disor-
ders with headache including migraine. Continuous
stimulus ascending from visceral afferents leads to the
central sensitization of trigeminocervical nuclear com-
plex expressing a parasympathetic referred pain in the
head (57). Reflux of gastric contents into esophagus in
GERD may be one example of chronic visceral stimulus
leading to sensitization and referred headache. This the-
ory may also be applicable for patients with IBS, who
have various somatic complaints in addition to their GI
symptoms. Migraineurs and patients with IBS may have
a very sensitive central and enteric nervous system,
which have turned hypervigilant through time and may
show exaggerated responses to unpleasant stimuli (58).
- Serotonin:
The neurotransmitter serotonin is present in the CNS
and in the nervous system within the GI tract. Seroto-
ninergic drugs are shown to have regulatory effects on
gastric motility, and have been proven beneficial in mi-
graine treatment and prophylaxis. Serotonin hypothesis
may therefore be another explanation for the comorbid-
ity of headache and GI abnormalities such as dyspepsia
and IBS (14, 59). Serotoninergic pathways may repre-
sent the target for the treatment of patients suffering
from both conditions.
- Autonomic nervous system (ANS) dysfunction:
ANS dysfunction is shown to be present in both head-
ache and GI complaints. The role of ANS is implicated in
postprandial gastric accommodation, thus ANS dysregu-
lation may result in delayed gastric emptying and dis-
motility-like dyspepsia. In addition, migraineurs are
demonstrated to suffer from chronic ANS dysfunctions
(4, 9, 60) and are noted to have gastric stasis even out-
side acute attacks (15, 16). This phenomena, however,
may be more prominent in migraineurs with dyspeptic
symptoms in the interictal period, but interictally symp-
tom free patients, may have normal gastric morphology
and accommodation (61-63). The ANS also has a role in
the pathopysiology of GERD in which the lower esopha-
geal sphincter is hypotensive or has increased transient
relaxations (10).
- Calcitonin gene-related peptide (CGRP):
CGRP is demonstrated to increase during migraine at-
tacks (64-66). This neuropeptide is a potent vasodilator
of intracranial vessels (67) and mediates pain transmis-
sion in the CNS (68). Infusion of this neuropeptide can
induce migraine attack in migraineurs (69). The seroto-
nin receptor agonist sumatriptan, which is administered
to manage the acute bouts of migraine, is suggested to
act partly by blocking the release of CGRP (70).
In addition, this neurotransmitter helps to regulate gas-
tric relaxations in response to ingestion of food or liquid.
CGRP has been shown to have a role in disorders of the
gastric reservoir functions leading to functional dyspep-
sia with anorexia and early satiety (4, 10). CGRP there-
fore, may have a role in the association of migraine and
GI disorders.
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Noghani et al
178
- Vasculopathy:
Vascular tone dysfunction and abnormal regional cere-
bral blood flow is demonstrated in migraineurs affected
by CD or H. Pylori (35, 37, 42, 71, 72). Since CD arises
from an autoimmune response against tissue transglu-
taminase it is postulated that the same interaction may
take place against this enzyme within the brain vascular
endothelium leading to various neurologic symptoms
observed in patients with CD (36, 73, 74). This theory,
however, may be more applicable for adults than pediat-
ric patients (33).
In H. Pylori infection, the immune system interacts with
the bacterium and vasoactive agents are released. It is
hypothesized that this phenomenon may in turn lead to
a systemic vasculopathy and alterations of vascular per-
meability in various sites including the intracranial ar-
teries. This phenomenon along with the production of
oxidants and nitric oxide results in regional cerebral
blood flow changes; hence inducing migraine headaches
(39, 42, 44). The role of oxidative stress however, has re-
cently been questioned (75).
- Food Allergy:
The role of food allergy in the activation of the immune
system and subsequent inflammation has been the sub-
ject of study for decades (76). Allergy to certain food an-
tigens and the development of IgE and IgG antibodies
may lead to an inflammation response which can play a
role in the pathophysiology of migraine and IBS (77, 78).
It is demonstrated that migraineurs are positive for IgG
food allergens more frequently than control subjects and
their symptoms may improve with an elimination diet
(79). In recent years, studies have focused on the IgG-
based elimination diet for migraineurs and also IBS pa-
tients and successful results have been reported in the
attenuation of symptoms (80-82). This supports the the-
ory that inflammation may play a key role in the patho-
physiology of migraine and may help to explain the
comorbidity of primary headaches and GI complaints.
The “Persian Medicine”
Traditional medicine is the sum of all the knowledge and
practices used in diagnosis, prevention, and elimination of
physical, mental, or social imbalance; relying exclusively
on practical experience and observation handed down
from generation to generation whether verbally or in writ-
ing(83).
Traditional medicine (TM) is growing more and more
popular worldwide (84). The affordability and accessi-
bility of this system along with concerns regarding side
effects of chemical drugs and management of chronic de-
bilitating diseases such as cancer, diabetes, and heart
disease has led many patients to become more inter-
ested in TM (85).
The TM practiced in Iran, called the “Persian Medicine”
(PM), which is known as Greeko-Arabic (Unani) medi-
cine elsewhere (86) has a history of more than 8000
years (87). The underlying physiological concept in PM
is that of the “Humoral Theory” which is in coordination
with the teachings of the ancient Greek scholars namely
Hippocrates (460-370 BC) and Galen (129-199 AD). The
Humoral Theory states that there are four types of basic
particles from which all elements are made. They act on
each other and finally make up the humors, which in turn
constitute the body organs. Thus, according to this the-
ory, health results from the balance of humors within the
body and their imbalance leads to disease. Humors are
four in number named "Dam" (Sanguis or Blood), the
quality of which is warm and moist, "Balgham" (Phlegm)
which is cold and moist, "Safra" (Choler or Yellow Bile)
which is warm and dry, and "Soada" (Melancholer or
Black Bile) which is cold and dry (88, 89).
Medieval medical science was gathered by ancient phy-
sicians, the most influential of which were Râzi (Rhazes,
860-940 AD) and Ebn-e-Sina (Avicenna, 980-1037 AD)
and they added to that their own observations and expe-
rience (90).
Ebn-e-Sina wrote more than 100 books in his short life
span, 16 of which were on medicine (91). His master-
piece the “Al-Qanoon fi al-Teb” (The Canon of Medicine)
became the principle medical textbook and was taught
and studied in universities of Europe and Asia from the
twelfth century until the end of the seventeenth century
(92). Partly, statements in this book still have relevance
today in different issues of health and disease (93-97).
Ebn-e-Sina has described headache disorders and thor-
oughly discussed the etiology, pathophysiology, symp-
toms, and various treatments on this issue, in the third
volume of the Qanoon.
In this book, headache disorders, referred to as "Soada",
are classified into 28 types with each having unique di-
agnostic criteria and treatment protocols. Some types
are classified as headaches originating from different or-
gans which have neurovascular communications with
the CNS. One of the most important of these organs was
believed to be the stomach, and gastric abnormalities
were considered one of the most common etiologies for
headache disorders in general (88).
Râzi also describes in his book the Al-Hawi (Continents),
a kind of headache originating from the stomach due to
the production of bitter humors in the gastric fundus.
Symptoms aggravate during fasting especially after wak-
ing up in the morning (90).
Headaches originating from the stomach are classified
into seven subtypes. These seven kinds of headache are
described here in brief and their key symptoms, aggra-
vating and relieving factors of each kind, are summa-
rized in Table 2.
The first type is headache due to abnormal quality of the
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179
Emergency (2016); 4 (4): 171-183
humors within the stomach. Excess warmth, cold, dry-
ness, or moisture of the humors within the stomach may
induce headaches. Once the normal qualities are reestab-
lished headache is relieved.
Imbalance of humors within the stomach comprises the
second to fourth type. Excess Safra, Balgham, or Soada in
the gastric cavity may lead to mucosal injury and gastric
dysfunction. Patients with headache due to excess Soada
may also present with manifestations of accumulation of
Soada within the CNS and therefore, suffer from mood
disorders. Another type is headache due to the produc-
tion of excess gas as a result of ingestion of gas producing
foods such as leguminous seeds. In the first stages, pa-
tients may experience epigastric pain just before the ini-
tiation of headaches, and once the abdominal pain and
bloating is resolved, the headache improves. The sixth
type is headache due to the production of excess vapor
in the stomach resulting from ingestion of certain kinds
of vegetables capable of producing vapors after gastric
digestion. The vapors were considered to ascend to the
Table 2: The seven types of headache arising from abnormalities within the stomach
Etiology
Key symptoms
Aggravating
factors
Relieving factors
Treatmenta
Abnormal quality
of humors
headache occuring af-
ter heavy meals
Overeating
Eating less; prokinet-
ics
Restoration of the
normal quality
Excess Safra
(Choler or Yellow
Bile)
Nausea; anorexia; bit-
ter taste in the mouth;
excess thirst; subic-
teric sclera; epigastric
burning
Starving; Safra
producing
foodsb
Avoiding hunger; vom-
iting the excess Safrac
Clearing the stom-
ach from exces-
sive humor
Excess Balgham
(Phlegm)
Increased salivation;
regurgitation; bloat-
ing; anorexia; de-
creased thirst
Overeating;
Balgham pro-
ducing foodsd
Starving; vomiting the
excess Balgham; Sleep;
prokinetics
Clearing the stom-
ach from exces-
sive humor
Excess Soada
(Melancholer or
Black Bile)
Food craving; epigas-
tric burning; regurgi-
tation
Anxiety; depres-
sion; Soada pro-
ducing foodse
Relaxation; vomiting
the excess Soada
Clearing the stom-
ach from exces-
sive humor
Excess luminal
gas
Frontal headaches; ab-
dominal pain; bloating
Gas producing
foods
Avoiding gas produc-
ing foods
Elimination of the
excess gas
Excess vapors
Pounding headaches;
vertigo; tinnitus
Vapor producing
foods (onion,
garlic, pepper,
and spicy vege-
tables)
Avoiding vapor pro-
ducing foods;
consuming coriander
after meals
Elimination of the
excess vapor;
blocking the as-
cent of vapors to
the brain
Weakness of the
gastric fundus
and the cardia
Headache occurs dur-
ing hunger especially
when waking up in
the morning; irritabil-
ity
Starving; walk-
ing under the
sun while hun-
gry; malodorous
smells
Avoiding hunger and
having breakfast in
time; avoiding CNS
stimulants; avoiding
malodorous smells
Strengthening the
fundus and the
cardia
a, Treatment methods presented were carried out by appropriate foods and natural drugs.
b, Spicy and salty foods, foods fried in oil, eggs, nuts, grapes, coconut, honey.
c, Certain drugs were used to induce vomiting. patients experienced rapid relief of headache afterwards.
d, Fish, milk, yogurt, cheese, cucumber, tomato, lettuce, watermelon, strawberry, sour cherry, kiwi, drinking water with meals.
e, Beef, pork, fish, sausages, ham, eggplant, lentil, potato, mushroom, sour tasting fruits, barley, black tea, coffee.
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Noghani et al
180
brain and induce headaches. Patients may also experi-
ence anorexia, nausea, and indigestion following the in-
gestion of such vegetables (Table 2). The seventh type is
headache due to weakness of the gastric fundus. The fun-
dus and the cardia have inadequate strength, gastric vis-
ceral sensory thresholds are decreased, and patients
have gastric hypersensitivity. Patients are also easily ir-
ritated in response to unpleasant stimuli (Table 2).
Each of these seven subtypes of headache are clearly de-
fined and thoroughly described by ancient scholars in
medieval medical resources and treatment regarding
each kind is provided (88, 98). The pathophysiology un-
derlying these types of headache is explained in the con-
text of the Aristotle philosophy and the humoral theory.
Nevertheless, they may correspond to the neurovascular
mechanisms postulated today for explaining the patho-
physiology of headache disorders associated with GI ab-
normalities such as central sensitization, vasculopathy,
and alterations in the regional cerebral perfusion.
Patients presenting with primary headache associated
with gastric dysfunction (especially dyspepsia), if thor-
oughly questioned, may be recognized to fit in with one
of the seven types of headache disorders above. If this is
the case, then they may undergo remission with the in-
stitution of the appropriate treatment. This is exactly
what is taking place today in PM offices in Iran.
Summary
Comorbidity of headache and GI abnormalities has be-
come a subject of interest to researchers in recent years.
There is evidence supporting the association of various
GI disorders with primary headaches classified by the
IHS. In addition to functional GI diseases, IBD and CD
along with H.Pylori infection are also reported to be pre-
sent in a substantial number of patients with headache.
Furthermore, there is a growing body of literature
demonstrating improvement or resolution of headache
following management of the accompanying GI disorder.
This raises the idea of existence of a possible unique di-
agnostic entity in the classification of headache disor-
ders, the “Headache of Gastrointestinal Origin”. This was
once believed by ancient scholars namely Râzi and Ebn-
e-Sina. They practiced treatment of this kind of headache
in their patients and expressed their experiences in their
writings. This entity may provide explanation for head-
aches which resolve following treatments targeting the
associated GI disorder. Efforts should be made to clarify
this type of headache, however arriving at a strict crite-
ria may be challenging.
Patients fulfilling criteria for any type of primary head-
aches through the ICHD, should be thoroughly ques-
tioned about GI symptoms. If any GI abnormality, either
functional or organic, is detected, especially outside the
bouts of headaches, treatment targeting the GI abnor-
mality is instituted. Once the GI abnormality is managed,
symptoms of the primary headache are reevaluated. If
headaches are improved or completely resolved, the
headache would be the one of gastrointestinal origin and
the patient may be given the diagnosis of “Headache at-
tributed to GI disorders”.
Acknowledgments:
The authors would like to thank Dr. R Choopani for his
helpful suggestions.
Conflict of interest:
The Authors declare that they have no conflict of inter-
est.
Funding support:
None.
Authors’ contributions:
All authors passed four criteria for authorship contribu-
tion based on recommendations of the International
Committee of Medical Journal Editors.
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... In patients with both migraine and GI disorders, the absorption of migraine medications may be decreased due to GI disorders, or GI symptoms may become more severe in patients taking migraine medications [10]. In addition, it has recently been reported that the relationship between the two diseases was due to the bidirectional relationship between the GI nervous system and the central nervous system called the gut-brain axis [11]. If GI diseases could cause migraine, it may play an essential role by treating GI diseases or through proper intestinal bacterial growth. ...
... Serotonin activates a neurotransmitter in the enteric nervous system and influences intestinal motility and inflammation [34,35]. Thus, the serotonin pathway can be a target for treating patients with both diseases [11]. ...
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Migraine is a common disease worldwide, and recent studies showed that the incidence of migraine was increased in patients with gastrointestinal (GI) diseases. In addition, preclinical evidence suggested a bidirectional relationship between the GI nervous system and the central nervous system called the gut–brain axis. This study aimed to determine the association between several high-prevalence GI diseases and migraine. Patients diagnosed with migraine or GI diseases were classified as the patient group at least twice a year. We included peptic ulcer disease, dyspepsia, inflammatory bowel disease, irritable bowel syndrome, and gastroesophageal disease as GI diseases. A total of 781,115 patients from the HIRA dataset were included in the study. The prevalence of migraine was about 3.5 times higher in patients with one or more GI diseases after adjusting for age, gender, and insurance type (adjusted odds ratio (ORadj = 3.46, 95% CI: 3.30–3.63, p < 0.001). In addition, the prevalence of migraine was increased as the number of comorbid GI diseases increased. The prevalence of GI disease was also higher in patients with medication for migraine, both preventive and acute treatment, compared to patients with either acute preventive or acute treatment. There was a statistically significant association between the prevalence of GI diseases and migraine, and the higher the number of accompanying GI diseases, the higher the correlation was in patients using both preventive and acute treatment drugs for migraine.
... Other studies also showed that all of the GI complaints are present among individuals with nonmigraine headaches like those with migraine headaches, and the frequency of these headaches was found to be increased by increasing GI disturbances [12]. Taken together, these various lines of evidence support the notion that ''GI headache" should be considered as a distinct diagnostic entity in the classification of headache disorders [13]. ...
... Based on PM theories, abnormal digestion, which leads to the production of abnormal and harmful substances, can be one of the most important causes of gastric headache. Decreases in gastric visceral sensory thresholds (gastric hypersensitivity) is another probable mechanism in PM [13]. ...
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The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal (GI) disorders. In Persian medicine (PM), physicians believed gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM. Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. PubMed, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family. Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose, apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer, antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities. However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.
... The traditional Persian physicians, Avicenna and Rhazes, believed in a type of headache caused by gastrointestinal problems [2]. In recent decades, a number of research centers around the world have focused their attention and research on the relationship between diseases or disorders of the digestive tract and extragastric diseases and symptoms [3]. ...
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The aim of this study was to investigate the relationship between gastrointestinal (GI) symptoms and extragastric manifestations such as headache, fatigue, and dizziness. A prospective cohort study was conducted in a tertiary hospital in Athens, where patients with GI problems and extragastric symptoms were treated only for their GI problems, and improvement in extragastric manifestations was recorded. Inclusion criteria were an age older than 18 years, the presence of at least one of the three extragastric symptoms investigated in this study (headache, dizziness, and fatigue), and the concomitant presence of at least one gastrointestinal symptom (e.g., nausea, belching, abdominal tenderness, epigastric pain, halitosis, flatulence, diarrhea, bad odor of flatulence, flatulence, and constipation). A standardized questionnaire was used to collect demographic data (such as age, weight, and height), patients’ symptoms, laboratory findings (gastric biopsy, gastroscopy, and colonoscopy), and intensity/frequency of GI and extragastric symptoms. Statistically significant associations were found between GI symptoms (nausea, constipation, halitosis, and belching) and dizziness, fatigue, and headache (frequency, intensity, and duration). Treatment of GI problems resulted in a significant improvement in extragastric symptoms within one month of treatment initiation. It should be emphasized that the actual reason for the improvement in extragastric symptoms was solely the resolution of the GI problems, as patients did not receive specific treatments for headache, dizziness or fatigue, or other changes in daily life. This study demonstrates the association between extragastric manifestations and GI disorders.
... Headache is one of the most common reasons for neurological clinic visits. In some cases, despite all the diagnostic and treatment measures, the cause of the headache cannot be determined and only symptoms are treated (1). ...
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Background Headache disorders are classified as primary or secondary; however, among the secondary headaches, those attributed to food ingestion are not well understood. Therefore, we conducted this study to describe and characterize a new headache entity that occurred during the holy month of Ramadan. This headache occurred within 4 h of breaking the fast. Methods This is a nationwide descriptive community-based cross-sectional study conducted during the last 10 days of Ramadan, based on a random sample of adults living in Saudi Arabia. The demographic data, headache symptomatology, nature and distribution of the pain, possible triggering and relieving factors, and patient management programs were analyzed. Results Completed questionnaires were obtained from 16,031 participants. Of those, 3147 (19.6%) reported headaches after breaking the fast in Ramadan. In 84.1% of cases, there was no previous diagnosis of headache or migraine. The characteristics of these postprandial fasting-related headaches mostly was episodic in nature (72%). The nature of the headache was variable, mostly heaviness or tightness (53.9%). Triggering factors included ingestion of fried food in (45%) and coffee (26.3%). Lying down and sleeping was found to be an important relieving factor (61%). Conclusion A new headache entity is being described. Appears to be quite common, occurs less than 2 h following the first meal, and is mostly of the heaviness and tension type.
... Referred pain is also observed in UC and CD patients 5,9 and IBD can be associated with a variety of other extraintestinal manifestations 10 . For instance, there is a significant association of migraine with IBD 11 , and treatment of gastrointestinal (GI) disorders has been found to improve headache/migraine symptoms [12][13][14] . ...
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Pain evoked by visceral inflammation is often ‘referred’ to the somatic level. Transient receptor potential ankyrin 1 (TRPA1) has been reported to contribute to visceral pain-like behavior in dextran sulfate sodium (DSS)-evoked colitis. However, the role of TRPA1 in somatic component of hypersensitivity due to visceral inflammation is unknown. The present study investigated the role of TRPA1 in colitis-evoked mechanical hypersensitivity at the somatic level. Colitis was induced in mice by adding DSS to drinking water for one week. Control and DSS-treated mice were tested for various parameters of colitis as well as mechanical pain sensitivity in abdominal and facial regions. DSS treatment caused mechanical hypersensitivity in the abdominal and facial skin. Pharmacological blockade or genetic deletion of TRPA1 prevented the colitis-associated mechanical hypersensitivity in the abdominal and facial skin areas although the severity of colitis remained unaltered. DSS treatment increased expression of TRPA1 mRNA in cultured dorsal root ganglion (DRG) neurons, but not trigeminal ganglion neurons, and selectively enhanced currents evoked by the TRPA1 agonist, allyl isothiocyanate, in cultured DRG neurons. Our findings indicate that the TRPA1 channel contributes to colitis-associated mechanical hypersensitivity in somatic tissues, an effect associated with upregulation of TRPA1 expression and responsiveness in DRG nociceptors.
... Some previous studies showed that many GI diseases were related to primary headache syndromes including migraine, to such an extent that Noghani et al. conducted a narrative review study entitled "Gastrointestinal Headache." [13] The results of the current study revealed a significant association between H. pylori infection and migraine. H. pylori infection was approved by RUT with respect to its sensitivity and cost-effectiveness. ...
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Background: Migraine is a common disorder which affects quality of life. There has been an increasing interest for discovering the association of gastrointestinal (GI) disorders with migraine during past years. This study aims to evaluate the association of Helicobacter pylori contamination, gastroesophageal reflux disease (GERD), gastric ulcer (GU), and duodenal ulcer (DU) with migraine in patients who underwent upper GI endoscopy due to refractory dyspepsia. Materials and methods: In this observational cross-sectional study, 341 dyspeptic patients who underwent upper GI endoscopy in Shahid Beheshti Hospital, Qom, Iran, included during 2016-2018. A checklist was used for collecting demographics, symptoms, and results from endoscopy and H. pylori testing. Diagnosis of migraine was made according to the International Headache Society criteria in patients who had headache. Data were analyzed using Chi-square and independent samples t-tests in SPSS 16 (SPSS Inc., Chicago, IL, USA) with P < 0.05 as significance level. Results: Among 341 patients, 141 (% 41.3) were male and 200 (58.7%) were female. 149 (43.7%) patients were diagnosed with migraine, from which 48 (32.2%) were male and 101 (67.8%) were female. The observed difference in migraine prevalence among male and female was statistically significant (P = 0.003). 198 (58.06%) patients were H. pylori contaminated, among these 138 (69.7%) suffered from migraine. Among 143 H. pylori-negative patients, there were 11 (7.7%) migraineurs. The difference in the prevalence of migraine among H. pylori positive and negative patients was significant. H. pylori and GERD were associated with migraine with P < 0.001. Patients with DU were more commonly suffering from migraine (P = 0.001). The association in patients with GU was not statistically significant (P = 0.863). Conclusion: Migraine might be associated with GERD, H. pylori infection, and DU, and the treatment of the underlying GI disorder may control headaches.
... Also, releasing of unknown chemicals by the stomach could be another explanation for GRV. There is evidence of a relationship between the brain and stomach; types of gastric-related headaches have also been reported in addition to GRV (32). In recent studies, a relationship between the brain and the digestive tract has been considered though gut-brain axis, some diseases such as Alzheimer's disease (33), anxiety and depression (34), multiple sclerosis, autism, stress (35) and dementia (36) which are recently proposed "may begin in the gut". ...
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Background: Chronic vertigo is a frustrating and expensive disease affecting individuals and society. Scientists of Traditional Persian Medicine (TPM) have a long held belief that there is a common type of vertigo originated from the stomach known as gastric related vertigo (GRV) and there are present, simple and low-cost treatments for GRV based on its categorization. Objective: To develop a valid tool for assessing GRV and determining the prevalence of this type of vertigo. Methods: In this cross-sectional study, a questionnaire was designed based on GRV indices. To determine the intra-rater reliability, a test- retest method was used and kappa coefficient was measured by Statistical Package for the Social Sciences software (SPSS, version 17). Content validity ratio (CVR) and content validity index (CVI) for each question were calculated by using Lawshe table. The reliable version of the questionnaire was assessed in a sample of 135 patients with a chronic true vertigo which lasts more than three months and aged between 18 and 65 years. This study was conducted in the outpatient clinics of several university hospitals in Tehran, Iran, between May 2016 and November 2017. Results: A valid 30-item questionnaire with CVR more than 0.62, CVI more than 0.78 and kappa coefficient more than 0.7 was the main achievement of this study, which can be useful for assessment of GRV in future clinical trials. The study showed that 98 participants (72.59%) had at least one criterion of GRV. Conclusion: According to the high prevalence of GRV among patients who suffer from chronic vertigo, more studies in this field including clinical trial are suggested.
... However, the scientific literature investigating mechanisms underlying the comorbidity of the two conditions is scant. Hypotheses explaining this association implicate central sensitization and parasympathetic referred pain, serotonin pathways, ANS dysfunction, systemic vasculopathy, and food allergies (48). In a previous study investigating associations between headache presence and cellular changes in the gastroduodenal mucosa, the presence of headache associated with dyspeptic symptoms was strongly related to mucosal mast cell density in pediatric patients with HP-negative functional dyspepsia. ...
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Background The brain and gastrointestinal (GI) tract are strongly connected via neural, endocrine, and immune pathways. Previous studies suggest that headaches, especially migraines, may be associated with various GI disorders. However, upper GI endoscopy in migraineurs has shown a low prevalence of abnormal findings. Also, the majority of studies have not demonstrated an association between Helicobacter pylori (HP) infection and migraine, although a pathogenic role for HP infection in migraines has been suggested. Further knowledge concerning the relation between headaches and GI disorders is important as it may have therapeutic consequences. Thus, we sought to investigate possible associations between GI disorders and common primary headaches, such as migraines and tension-type headaches (TTH), using the Smart Clinical Data Warehouse (CDW) over a period of 10 years.Methods We retrospectively investigated clinical data using a clinical data analytic solution called the Smart CDW from 2006 to 2016. In patients with migraines and TTH who visited a gastroenterology center, GI disorder diagnosis, upper GI endoscopy findings, and results of HP infection were collected and compared to clinical data from controls, who had health checkups without headache. The time interval between headache diagnosis and an examination at a gastroenterology center did not exceed 1 year.ResultsPatients were age- and sex-matched and eligible cases were included in the migraine (n = 168), the TTH (n = 168), and the control group (n = 336). Among the GI disorders diagnosed by gastroenterologists, gastroesophageal reflux disorder was more prevalent in the migraine group, whereas gastric ulcers were more common in the migraine and TTH groups compared with controls (p < 0.0001). With regard to endoscopic findings, there were high numbers of erosive gastritis and chronic superficial gastritis cases in the migraine and TTH groups, respectively, and the severity of gastritis was significantly higher in patients with TTH compared with controls (p < 0.001). However, no differences were observed in the prevalence of HP infection between the groups.Conclusion The observed association in this study may suggest that primary headache sufferers who experience migraines or TTH are more prone to GI disorders, which may have various clinical implications. Further research concerning the etiology of the association between headaches and GI disorders is warranted.
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Background Migraine is a complex neurological disorder that is considered the most common disabling brain disorder affecting 14 % of people worldwide. The present study sought to infer potential causal relationships between self-reported migraine and other complex traits, using genetic data and a hypothesis-free approach. Methods We leveraged available summary statistics from genome-wide association studies (GWAS) of 1,504 phenotypes and self-reported migraine and inferred pair-wise causal relationships using the latent causal variable (LCV) method. Results We identify 18 potential causal relationships between self-reported migraine and other complex traits. Hypertension and blood clot formations were causally associated with an increased migraine risk, possibly through vasoconstriction and platelet clumping. We observed that sources of abdominal pain and discomfort might influence a higher risk for migraine. Moreover, occupational and environmental factors such as working with paints, thinner or glues, and being exposed to diesel exhaust were causally associated with higher migraine risk. Psychiatric-related phenotypes, including stressful life events, increased migraine risk. In contrast, ever feeling unenthusiastic / disinterested for a whole week , a phenotype related to the psychological well-being of individuals, was a potential outcome of migraine. Conclusions Overall, our results suggest a potential vascular component to migraine, highlighting the role of vasoconstriction and platelet clumping. Stressful life events and occupational variables potentially influence a higher migraine risk. Additionally, a migraine could impact the psychological well-being of individuals. Our findings provide novel testable hypotheses for future studies that may inform the design of new interventions to prevent or reduce migraine risk and recurrence.
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BACKGROUND Migraine is one of the prevalent headaches. Many of patients with migraine, complain of gastrointestinal symptoms. There is limited studies on relation of gastrointestinal symptoms and migraine headache at population level. METHODS In this population-based study, 1038 subjects older than 15 year from a rural area in Fars province, south of Iran. were investigated for functional gastrointestinal disorders. By cluster random sampling, 160 of these persons invited to receive endoscopy along with histopathology samples of upper gastrointestinal tract. Data were analyzed using Pearson chi-square and Fisher exact. RESULTS Mean age of participations were 34.3 years with female to male of 3:1. The prevalence of migraine, irritable bowel syndrome (IBS), reflux, and dyspepsia were 24.6%, 17.7%, 17.4%, and 32.1%, respectively. There were significant relationship between migraine and functional gastrointestinal diseases (odds ratio of association for migraine with IBS, reflux, and dyspepsia were 3.43, 1.68, and 1.68 with p-value < 0.001 for all). In endoscopic findings, only presence of hiatal hernia was associated significantly with migraine (p = 0.011). No histopathologic findings in antral or duodenal biopsies were associated with migraine. CONCLUSION In this population based study we found significant association between migraines and gastrointestinal functional disorders including IBS, reflux and dyspepsia. This may have implication in better management of patients with migraine headache.
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Background: Recent studies have shown a positive correlation between Helicobacter pylori infection and migraine headache. The aim of this study was to evaluate the role of H. pylori infection in migraine headache with (MA) and without aura (MO). Methods: This is a case-control study containing information on 84 patients (including MA, MO) and 49 healthy individuals. The enzyme-linked immunosorbent assay (ELISA) test was used to measure immunoglobulin G (IgG,) immunoglobulin M (IgM) titer in two groups. Headache severity was evaluated according to Headache Impact Test (HIT6) questionnaire. Results: Mean ± SD of IgM antibody in Migrainous patients 26.3 (23.1) showed significantly difference with control group 17.5 (11.2) (P = 0.004). In addition, the mean ± SD HIT6 in Migrainous patients differed significantly between MA and MO groups 65.5 (4.7), 54.9 (5.3) respectively, P < 0.001). The only significant correlation was found for IgG antibody and HIT6 in MA patients (r = 0.407, P = 0.011) and MO group (r = 0.499, P = 0.002). The risk of migraine occurrence in patients did not significantly associate with the level of IgG and IgM antibodies. Conclusion: The results give a hope that definite treatment and eradication of this bacterium could be a cure or to reduce the severity and course of migraine headaches.
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Many patients presenting with headache also complain of constipation; the relationship between these two symptoms has not been explored in detail. The aim of this study was to investigate the association between primary headache and constipation. This retrospective study included all children who attended the Inje University Sanggye Paik Hospital complaining of headache, and who had been followed up for at least 100 days. Patients were divided into 2 groups: group A, in whom the headache improved after treatment for constipation, and group B, in whom headache was not associated with constipation. Of the 96 patients with primary headache, 24 (25.0%) also had constipation (group A). All 24 received treatment for constipation. Follow-up revealed an improvement in both headache and constipation in all patients. Group B contained the remaining 72 children. Comparison of groups A and B indicated a significant difference in sex ratio (P=0.009, chi-square test). Patients with probable tension-type headache were more likely to be in Group A (P=0.006, chi-square test). Resolution of constipation improves headache in many patients diagnosed with primary headache, especially those with probable tension-type headache. We suggest that either constipation plays a key role in triggering headache, or that both constipation and headache share a common pathophysiology.
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Background/Aims: Constipation and headache are prevalent conditions among children worldwide. Previous studies have shown the relationship between upper gastrointestinal complaints and headache in children. However, the association with lower gastrointestinal complaints such as constipation has not been investigated until present. The aim of this study is to evaluate the relationship between headache and chronic functional constipation in children aged 4-12 years old. Materials and Methods: This cross-sectional study has evaluated the prevalence of headache in 326 children in Shiraz, Iran 2012. All the subjects and their parents were interviewed based on a structured questionnaire for the diagnosis of constipation and headache. Children with constipation were selected from the Pediatric Gastroenterology Clinic Affiliated to the Shiraz University of Medical Sciences. The control group was selected from healthy children attending Shiraz schools. Diagnosis of headache and constipation were made based on the second Edition of The International Headache Classification (ICHD-2) and ROME III criteria, respectively. Results: Headache prevalence among children with constipation was significantly higher (19.8%) than that of the control group (5.6%) [Odds ratio (OR) 4.192, p<0.001], which was significant only in the non-migraine headache subtypes (15.1% vs 2.8%, OR 25, p<0.002). Among the headache subtypes of different severity (mild, moderate, severe), only mild headache was significantly more prevalent in constipated children (14.9% vs. 1.4%, in the control group, respectively, p<0.001). Conclusion: This study revealed a strong correlation between headache and chronic functional constipation, which can result from the effect of these comorbid conditions with emotional stress, depression, and anxiety.
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Migraine is frequently accompanied by symptoms consistent with functional gastrointestinal disorders (FGIDs). This study evaluated the prevalence of functional gastrointestinal symptoms and assessed the symptoms' relationship with the concomitant functional symptoms of anxiety, depression, and headache-related disability. This prospective study included 109 patients with migraine who were recruited from a headache clinic at a teaching hospital. The participants completed a self-administered survey that collected information on headache characteristics, functional gastrointestinal symptoms (using Rome III criteria to classify FGID), anxiety, depression, and headache-related disability. In total, 71% of patients met the Rome III criteria for at least one FGID. In patients with FGID, irritable bowel syndrome was the most common symptom (40.4%), followed by nausea and vomiting syndrome (24.8%) and functional dyspepsia (23.9%). Depression and anxiety scores were significantly higher in patients meeting the criteria for any FGID. The number of the symptoms consistent with FGID in individual patients correlated positively with depression and anxiety. FGID symptoms defined by the Rome III criteria are highly prevalent in migraine. These symptoms correlate with psychological comorbidities, such as depression and anxiety.