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Abstract

Background

Migraine is a condition frequently associated with gastrointestinal disorders. Previous reports have shown the relationship between irritable bowel syndrome and migraine, but no data are yet available in patients with functional dyspepsia. We therefore evaluated whether alteration of gastric sensorimotor activity may be related to migraine.

Methods

Sixty patients affected by functional dyspepsia, 38 with postprandial distress syndrome and 22 with epigastric pain syndrome were enrolled in a cohort study. Presence and severity of dyspeptic symptoms, migraine presence and severity, gastric sensitivity thresholds during fasting and postprandial period, gastric accommodation and gastric emptying time were evaluated.

Results

In epigastric pain syndrome, 12/22 (54%) patients suffered from migraine and this condition was never correlated with meal ingestion. In postprandial distress syndrome patients, 29/38 (76%) suffered from migraine, in 26/29 (89%) its onset was considered as meal-related, and migraine severity was significantly correlated with postprandial modification of the gastric discomfort threshold (r = −0.73; p < 0.001). In patients with postprandial distress syndrome, in the subgroup with moderate to severe migraine, the severity of fullness and early satiation was significantly higher than in patients with mild or absent migraine. In patients with moderate to severe migraine, gastric accommodation, sensitivity thresholds and gastric emptying time were similar to patients with mild or no migraine.

Conclusions

In patients with functional dyspepsia and postprandial symptoms, migraine is a very frequent comorbidity. On clinical grounds, it is associated with an increased severity of fullness and early satiation and, on pathophysiological grounds, it seems correlated with postprandial hypersensitivity.

Keywords

Migraine functional dyspepsia visceral sensitivity gastric tone barostat discomfort threshold

Introduction

In functional gastrointestinal disorders, extra-intestinal symptoms are frequently associated complaints. In irritable bowel syndrome, symptoms from the urinary tract, gynaecological sphere, skin but also neurological symptoms have proved to be significantly more prevalent than in controls (1). In particular, headache was detected in more than 30% of IBS patients (1). More recently, this figure was confirmed in an Asiatic population (2), and a higher prevalence was also reported in females. In day-to-day clinical practice, dyspeptic patients very frequently report the presence of headache or migraine in association with dyspeptic symptoms. However, we have no information from systematic studies on the relationship between functional dyspepsia and migraine, partly because in published data there is not always a clear distinction between headache and migraine.

Various subtypes of patients with different underlying pathophysiological mechanisms can be found among patients with functional dyspepsia: it was previously shown that particular clusters of symptoms may correlate with specific sensorimotor alteration of the stomach (3 –8), but unfortunately a great overlap among subgroups limited the clinical value of this observation (9,10). Rome criteria for diagnosis of functional gastrointestinal disorders (11,12) described two new entities to improve pathophysiological and therapeutic research: postprandial distress syndrome (PDS), characterised by meal-induced dyspeptic symptoms, in particular fullness and early satiation, and epigastric pain syndrome (EPS), not related to meal ingestion and mainly characterised by the presence of pain. In our clinical experience, migraine is frequent in patients suffering from a PDS. To our knowledge, information on the prevalence of migraine in patients with PDS and EPS are still lacking and studies dealing with the pathophysiological aspects of this possible association are not yet available. Accordingly, our working hypothesis was that migraine, an extraintestinal condition apparently not related to the gastrointestinal tract, may be associated with a specific subgroup of dyspeptic patients, sharing a common pathophysiological pathway.

The aim of this study, therefore, was to analyse the association between alterations of gastric sensorimotor activity and migraine. In particular, we tested whether an alteration of both fasting and postprandial tonic and phasic activity and sensitivity of the stomach may be associated with the presence of migraine, in accordance with diagnostic criteria for functional dyspepsia.

Patients and methods

Patients

Sixty consecutive HP negative patients (38 female, 22 male, mean age 38 ± 4 years) attending our outpatient clinic, suffering from functional dyspepsia and diagnosed according to the Rome III criteria (11), were enrolled. PDS was present in 38 patients and EPS in 22 patients. The two groups were comparable for age and gender and none of the patients showed an overlap between the two syndromes. None of the patients suffered from other functional gastrointestinal disorders or had undergone major abdominal surgery. Two cases of surgical correction of inguinal hernia and seven cases of appendectomy in adolescence were reported. None of these patients suffered from visceral adherence. In all the patients, upper gastrointestinal endoscopy was normal before enrolment. All the patients were studied at diagnosis. None were taking drugs known to interfere with gastric motility and sensitivity. This cohort of patients was the same as that enrolled in a previous paper of our group (13): the enrolment took 3 years, due to the difficulty in selecting these patients. As already indicated in our previous paper (13), 237 dyspeptic patients were screened and 177 were excluded due to co-existence of dyspepsia and gastroesophageal reflux disease (n = 55), the presence of helicobacter pylori (HP) positive dyspepsia (n = 44), the overlap of PDS and EPS (n = 25), the overlap of EPS and PDS (n = 51), the coexistence of HP-positive duodenal ulcer (n=2). In particular, a period of only 8 months was sufficient to enrol PDS patients, but we needed 3 years to select the subgroup of EPS patients without an overlapping PDS. In our previous paper, we showed a higher prevalence of both fasting and postprandial hypersensitivity in PDS than in EPS patients, lower gastric volume and compliance at fasting in EPS than in PDS, and similar gastric emptying time and accommodation between the two subgroups. Moreover, in PDS patients, symptom severity showed a significant and strict correlation with the extent of postprandial reduction of the discomfort threshold.

In addition to dyspeptic symptoms, all the patients underwent a clinical evaluation by an experienced neurologist at the University Centre for Adaptive Disorders and Headache of the Iistituto di Ricovero e Cura a Carattere Scientifico (IRCCS) “Casimiro Mondino” Hospital Foundation, to ascertain the presence of migraine, according to ICHD-3 beta criteria (14). Forty-one patients with migraine without aura were enrolled. According to ICHD-3 beta criteria (14), all the patients suffered from episodic migraine. On average, in all the patients, three to four attacks occurred in a month, lasting for a maximum of two days. Due to the aim of the study (13), patients taking triptans were excluded. An on-demand use of acetaminophen and/or NSAIDs was the usual treatment for all patients. The last symptomatic therapy was taken at least 3 months prior to the study. The use of NSAIDs was infrequent and could be not considered as responsible for dyspeptic symptoms. In six patients, beta-blockers had been previously prescribed, but they had been stopped at least 6 months before the study.

A migraine attack was defined according to ICHD-3 beta criteria (14): If not better accounted for by another ICHD-3 beta diagnosis, a headache lasting at least 4–72 hours, associated with at least two of the following: (a) unilateral location, (b) pulsating quality, (c) moderate to severe pain intensity, (d) aggravation by or avoidance of routine physical activity; associated to at least one of the following: (i) nausea and/or vomiting, (ii) photophobia and phonophobia. Nausea and vomiting were two frequent complaints during migraine attacks. However, both symptoms were two frequent dyspeptic symptoms in our cohort of functional dyspepsia patients.

Design of the study

On entry, all subjects underwent symptom evaluation. Gastric sensorimotor activity both during fasting and after the administration of a meal was performed by gastric barostat. The ¹³C-octanoic acid breath test was used to measure gastric emptying for solids.

Barostat test

After an overnight fast, patients underwent gastric barostat test to measure fasting and post-prandial gastric sensitivity, fasting and post-prandial gastric tone, and fasting and postprandial phasic activity.

A double lumen catheter (Salem sump tube 14 Ch., Sherwood Medical), equipped at its distal end with an infinitely compliant plastic bag (capacity 1200 ml, diameter 17 cm), was inserted in the stomach through the mouth and secured with adhesive tape to the chin. The catheter was connected to a barostat device (G & J Electronics Inc., Toronto, ON, Canada), a computer-driven programmable instrument that maintains a constant preselected pressure within the bag, modifying the air volume content by an electronic feedback mechanism. Accordingly, the instrument allows the monitoring of gastric motor activity (contraction or relaxation) as changes in intra-balloon volume (reduction or increase, respectively), as constant intra-balloon pressure (15). The balloon was gradually unfolded: With the subjects in a recumbent position, the balloon was initially inflated with 250 ml of air for 2 minutes and then completely deflated. After a 10-minute equilibration period, the patients assumed a comfortable sitting position (80° bent knees, trunk upright). Then, minimal distending pressure (MDP), defined as the lowest intra-bag pressure providing a 30 mL or greater intra-bag volume, was determined.

Sensitivity thresholds were determined with a sequential ramp distension sequence, starting from the MDP, in stepwise increments of 2 mmHg, lasting for 2 minutes. At the end of each distending step, the subjects were asked to score gastric sensations, using a graphic scale graded from 0 to 6 and combining verbal descriptors (16). The perception threshold was defined as the first level of intra-bag pressure that evoked a perception score of 1 or more and the discomfort threshold as the first level of intra-bag pressure that evoked a perception score of 5 or more (7). An intra-bag volume of 1000 ml, or the subject reporting discomfort or pain corresponding to a score of 5 or 6 respectively, fixed the end point of the distention sequence. A 15-min resting period then followed.

Fasting gastric tone was measured for a 30-min period with an intra-balloon pressure set at MDP+2. After oral administration of a liquid caloric meal (1 Kcal per ml, 19% fat, 41% carbohydrate, 40% protein, 200 ml total volume, 200 Kcal) postprandial gastric tone was measured for 60 minutes and meal-related modifications of gastric tone were detected as volume changes. A further resting period of at least 15 minutes then followed and a postprandial series of isobaric distentions allowed the evaluation of postprandial sensitivity thresholds as perception and discomfort thresholds.

Gastric emptying study

With the previously validated ¹³C-octanoic acid breath test (17), at 8.00 a.m. after an overnight fast, gastric emptying for solids was measured. A scrambled egg, 60 g of white bread and 150 ml of water, adding 100 mg of 13C-Octanoic acid to the egg yolk, represented the test meal. A breath sample was collected in fasting condition and further samples were collected at 15-min intervals for a period of 240 min post-prandially. Gastric half-emptying time (T_1/2) was then calculated (17).

Symptom evaluation

A previously accepted dyspepsia questionnaire (6) was adopted to grade the presence and severity of seven different symptoms (epigastric pain, epigastric burning, fullness, early satiety, bloating, nausea, vomiting) according to a semiquantitative score (0 = no symptom, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms, interfering with daily activities). The severity of migraine was assessed by visual analogue scale (VAS) score (18). Patients were asked to consider the global severity of the migraine attack, without focusing on gastrointestinal symptoms. A score of 0 defined the absence of migraine, a score ranging from 0.1 to 3.3 defined a mild migraine, a score ranging from 3.4 to 6.6 defined a moderate migraine, and a score ranging from 6.7 to 10 defined a severe migraine.

Statistical analysis

The cohort of patients is the same previously enrolled for another study from our group (13). Study power and sample size calculation have been previously described (13).

Parameters of interest were fasting and postprandial perception and discomfort thresholds, and fasting and post-prandial gastric tone.

As previously specified, gastric tone was measured by monitoring the modifications of intra-gastric bag volume with intra-bag pressure set at MDP+2 mm Hg. Barostat frequency of volume and pressure sampling was 1/sec and the time-volume curve for each patient was calculated considering the mean volumes of the intragastric balloon during consecutive 5-min intervals. The mean volume of the 30-min fasting period was used to detect fasting gastric tone and, similarly, post-prandial gastric tone was calculated as the mean volume of the 60-min post-prandial period. The difference between the average volumes during the 30-min fasting period and 60-min post-prandial period was used to quantify the meal-induced gastric tone modification.

We had no missing data. Data are presented as mean ± SD. The Kolmogorov-Smirnov normality test was performed to evaluate the distribution of data. All data showed a parametric distribution and were compared by Student's t-test. The level of association between two variables was determined by Pearson's correlation coefficient. Differences were considered significant at the 5% level.

Results

Prevalence of migraine

Migraine without aura was present in 41 out of 60 dyspeptic patients (68%). In EPS, 12/22 (54%) patients suffered from migraine without aura. In none of these patients was the occurrence of migraine correlated with meal ingestion. Six patients reported that the occurrence of migraine was associated with a subsequent onset of dyspeptic symptoms, in particular nausea and, rarely, vomiting.

In PDS, migraine was present in 29 out of 38 patients (76%) and in 26 out of 29 patients (89%) migraine attacks were correlated with meal ingestion and were associated with dyspeptic symptoms.

The presence of migraine was not correlated with age or gender.

Migraine without aura and dyspeptic symptoms

In Table 1, the correlation between severity of symptoms and severity of migraine in patients with PDS and EPS is shown. A significant correlation between the severity of migraine and the two symptoms, fullness and early satiation in PDS patients, is evident. In patients with EPS, the severity of migraine was significantly correlated with epigastric burning, bloating, nausea and belching.

Table 1.

Correlation between severity of dyspeptic symptoms and severity of migraine in patients with postprandial distress syndrome and epigastric pain syndrome.

	Postprandial distress syndrome		Epigastric pain syndrome
	r	p	r	p
Epigastric pain	−0.07	NS	0.16	NS
Epigastric burning	−0.24	NS	−0.62	0.002
Fullness	0.39	0.01	−0.31	NS
Early satiety	0.38	0.01	0.10	NS
Bloating	0.16	NS	−0.56	0.006
Nausea	0.11	NS	−0.46	0.03
Belching	−0.24	NS	−0.52	0.01
Vomiting	−0.19	NS	−0.25	NS

In Table 2, the severity of dyspeptic symptoms in accordance with the severity of migraine is shown. In patients with PDS, patients with moderate to severe migraine showed significantly higher fullness and early satiation scores than patients with mild or no migraine. In patients with EPS, patients with severe migraine suffered from less severe epigastric burning and bloating than patients with mild or no migraine. Moreover, the comparison of the severity of epigastric pain, fullness and early satiety between patients with PDS and EPS in accordance with the severity of migraine, showed greater severity of epigastric pain in patients with EPS, and more severe fullness and early satiety in PDS.

Table 2.

Severity of dyspeptic symptoms in patients with postprandial distress syndrome and epigastric pain syndrome in accordance with the severity of migraine.

	Postprandial distress syndrome			Epigastric pain syndrome
	Moderate to severe migraine	Mild migraine	p	Moderate to severe migraine	Mild migraine	p
Epigastric pain	1.6 ± 1.0	1.6 ± 1.0	NS	2.2 ± 0.7	2.0 ± 0.4	NS
Epigastric burning	1.5 ± 1.0	1.7 ± 1.0	NS	0.7 ± 0.7	1.6 ± 0.8	0.008
Fullness	2.2 ± 0.7	1.9 ± 0.7	0.02	1.1 ± 0.8	1.5 ± 0.9	NS
Early satiety	2.0 ± 0.8	1.7 ± 0.8	0.01	1.3 ± 1.1	1.1 ± 1.3	NS
Bloating	2.2 ± 0.8	2.1 ± 0.8	NS	1.3 ± 1.0	2.3 ± 0.7	0.01
Nausea	1.7 ± 0.8	1.6 ± 0.9	NS	1.3 ± 1.3	2.3 ± 1.1	NS
Belching	1.2 ± 1.0	1.3 ± 1.1	NS	0.7 ± 1.1	1.5 ± 1.0	NS
Vomiting	1.2 ± 0.9	1.3 ± 1.0	NS	1.2 ± 1.3	1.7 ± 1.2	NS

Gastric sensitivity thresholds

In Table 3, fasting and postprandial sensitivity thresholds in accordance with the severity of migraine are shown.

Table 3.

Fasting and postprandial perception and discomfort thresholds in patients with postprandial distress syndrome and epigastric pain syndrome in accordance with the severity of migraine.

	Perception threshold			Discomfort threshold
	Fasting	Postprandial	p	Fasting	Postprandial	p
Postprandial distress syndrome
Migraine severity ≥ 2	5.6 ± 2.4	5.5 ± 2.5	NS	12.1 ± 3.8	9.3 ± 4.2	0.0001
Migraine severity ≤ 1	5.3 ± 2.1	5.2 ± 2.4	NS	10.1 ± 3.5	10.5 ± 4.8	NS
Epigastric pain syndrome
Migraine severity ≥ 2	4.7 ± 2.0	5.6 ± 2.0	NS	10.7 ± 2.8	9.8 ± 2.7	NS
Migraine severity ≤ 1	4.6 ± 1.7	4.5 ± 1.4	NS	11.2 ± 3.0	11.0 ± 3.6	NS

In patients with PDS, we and others have already shown the presence of a significant reduction of the postprandial discomfort threshold and a highly significant correlation between the severity of both fullness and early satiation with postprandial modification of the discomfort threshold (13,19). In this subgroup of patients, fasting and postprandial perception thresholds in patients with moderate to severe migraine was not significantly different in comparison with patients with mild or no migraine. On the contrary, the comparison between fasting and postprandial thresholds showed that a significant reduction of the discomfort threshold was evident only in the subgroup of patients with moderate to severe migraine.

In patients with EPS, the sensitivity thresholds did not show any significant difference in accordance with the severity of migraine or meal intake.

In patients with PDS, the severity of migraine was significantly correlated with the fasting discomfort threshold (r = 0.48, p < 0.05) and a highly significant correlation between the severity of migraine and postprandial modification of the discomfort threshold (r = −0.73, p < 0.001) was evident (Figure 1). Finally, in patients with moderate to severe migraine, the postprandial modification of the discomfort threshold was significantly correlated with the severity of fullness and early satiety (r = −0.50, r = −0.47, p < 0.05) and gastric emptying time for solids (r = −0.49, p < 0.05).

Figure 1.

Correlation between the severity of migraine and the postprandial modification of discomfort threshold in the PDS group.

Gastric emptying time for solids

In Table 4, mean gastric emptying time (T_1/2) in accordance with the severity of migraine in the two subgroups of patients is shown. In both PDS and EPS, mean gastric emptying time in patients with moderate to severe migraine was not significantly different in comparison with patients with mild or no migraine.

Table 4.

Mean gastric emptying time (T½) in patients with postprandial distress syndrome and epigastric pain syndrome in accordance with the severity of migraine.

	Postprandial distress syndrome	Epigastric pain syndrome	p
Migraine severity ≥ 2	139 ± 54	146 ± 61	NS
Migraine severity ≤ 1	130 ± 50	121 ± 30	NS

Gastric accommodation to meal

In patients with PDS and moderate to severe migraine, both mean fasting volume (190 ± 116 ml) and mean postprandial volume (447 ± 182 ml) were not significantly different from patients with mild or no migraine (206 ± 115 ml and 413 ± 180 ml, respectively). Fasting and postprandial fundic volumes were not correlated with the severity of migraine (data not shown).

In patients with EPS and moderate to severe migraine, both mean fasting volume (192 ± 97 ml) and mean postprandial volume (382 ± 225 ml) were not significantly different from patients with mild or no migraine (180 ± 59 ml and 354 ± 110 ml, respectively). Fasting and postprandial volumes were not correlated with the severity of migraine (data not shown).

Discussion

The relationship between dyspeptic symptoms and migraine is very complex. Several old reports hypothesised that abdominal symptoms might represent clinical manifestations of migraine, even in the absence of classic migraine (20,23) and, on several occasions, they may dominate the entire clinical presentation, inducing the patients to seek gastroenterological, and not neurological, consultation (24). Moreover, in the available data, a clear distinction between headache and migraine is not always available, which makes the comparison of results difficult.

It has previously been shown that in patients with migraine both acid exposure of the oesophageal mucosa and the endoscopic appearance of the upper gastrointestinal tract are not different from healthy controls (25), thus disproving the role of organic alteration in the pathophysiology of dyspeptic symptoms associated with migraine. Gastric stasis has also been described in migraine, both during attacks (26) and the interictal periods (27), suggesting the hypothesis that disorders of gastric function might be correlated with migraine. Moreover, a recent report suggested that other gastrointestinal disorders, such as gastroesophageal reflux disease and constipation, may also be responsible for migraine (28); irritable bowel syndrome was shown to be characterised by the presence of migraine in more than 30% of cases (1) and a further description reported an association in up to 50% of cases (29). There is no doubt that, in everyday life, the onset of migraine during dyspeptic episodes, even occasionally, is certainly an extremely common occurrence.

To better study the relationship between gastrointestinal disorders and migraine, we performed a wide evaluation of gastric sensorimotor function, comparing gastric function between dyspeptic patients with and without migraine. We subdivided the cohort of patients according to the Rome criteria which, for research purposes, suggested a division of dyspeptic patients into a subgroup characterised by the occurrence of symptoms after the ingestion of a meal (PDS) and a subgroup characterised by the presence of symptoms independent of the ingestion of a meal (EPS) (11,12). To avoid the interference of migraine treatment on gastric sensorimotor activity, patients taking triptans were excluded. It has been previously shown that triptans have a marked effect on gastric tone and sensitivity (30,31); however, this kind of patient selection may represent a limitation of the study, because it makes the cohort studied less representative of migraine patients.

Our results show that, in PDS patients, the main symptoms characterising this subgroup of patients were significantly correlated with the severity of migraine. On the contrary, in EPS patients, a significant correlation between the severity of migraine and dyspeptic symptoms was evident for epigastric burning, bloating, nausea and belching. Moreover, independently of the severity of migraine, the severity of fullness and early satiation were higher in PDS than in EPS and, similarly, the severity of epigastric pain was higher in EPS than in PDS. However, it is worth nothing that in these two syndromes the presence of more severe scores for migraine were associated with more severe scores of their main symptoms; that is to say, fullness and early satiation for PDS, and epigastric pain for EPS. These results suggest a strict association between the severity of dyspeptic symptoms and the severity of migraine in both syndromes.

We and others (13,19) have already shown that, regardless of the presence of migraine, patients with PDS show a significant reduction of discomfort threshold in the postprandial phase. In this subgroup of patients, we have now shown that the prevalence of migraine is higher than in patients with EPS and that migraine occurrence is very frequently associated with dyspeptic symptoms. Moreover, in PDS patients, but not in patients with EPS, the severity of migraine was strictly correlated with postprandial modification of the discomfort threshold. Finally, high scores for fullness and early satiation and gastric emptying time showed a significant correlation with postprandial modification of discomfort threshold. These results are very intriguing on pathophysiological grounds, as they indicate that gastric hypersensitivity occurring in the postprandial phase may be important in a subgroup of dyspeptic patients showing postprandial migraine.

The relationship between visceral and somatic hypersensitivity in functional gastrointestinal disorders was largely evaluated and a high prevalence of visceral sensitivity was reported (32). Moreover, it was recently shown that somatic hypersensitivity is present in 60% of patients at the upper and 30% at the lower extremity, and most patients with somatic hypersensitivity also show visceral hypersensitivity. Therefore, the presence of somatic hypersensitivity, as evidence of central sensitisation, may be detected in a remarkable portion of patients (33). However, this is not a hallmark of functional gastrointestinal disorders and it is not correct to hypothesise the presence of a generalised hypersensitivity syndrome.

Moreover, according to both Rome III and the recent revision Rome IV (11,12), the presence of epigastric pain is not necessary to diagnose functional dyspepsia. In particular, the subtype of functional dyspepsia patients characterised by postprandial symptoms are diagnosed on the basis of fullness and satiety. Accordingly, we are not surprised by the lack of association between epigastric pain and migraine presence or severity.

Gastric accommodation did not show any significant difference between the two groups of patients and the presence of migraine did not modify these results. This finding disproves a role for alterations in gastric tone in the pathophysiology of meal-related migraine.

The pathogenesis of migraine is largely unknown, and up to now none of the suggested hypotheses has been accepted. One of these theories suggests that migraine depends on a sequence of events, starting with a trigger event that mainly affects the cerebral vascular system. The electrical or mechanical stimulation of circle of Willis arteries induces the typical pulsating pain of migraine (34) and, during migraine attacks, a middle cerebral artery dilation occurs that is reverted by the administration of sumatriptan (35). More recently, in patients with migraine without aura, a central serotoninergic receptor hypersensitivity was shown (36), in particular consisting of an altered sensitivity of central 5-HT_1A receptors. Moreover, sudden modifications of systemic 5-HT levels have also been shown to be associated with migraine (37) and, in humans, 5-HT₁ receptor activity modulates sensorimotor activity of the stomach (38). It was recently shown that buspirone, a 5-HT_1A receptor agonist, improves gastric accommodation and the overall severity of symptoms in patients with functional dyspepsia, in particular fullness, early satiation and bloating (39).

It is therefore possible that in a subgroup of patients the trigger event is represented by the meal which, stimulating a hypersensitive stomach, promotes the occurrence of migraine. Until now, there have been no data suggesting the role of a specific neurological pathway for this mechanism. But the role of brain stem structures was recently analysed. During migraine attacks, an activation of periaqueductal gray contralateral to the pain site (40) was shown. Periaqueductal gray is considered a pivotal area of a descending sympathetic network in the brainstem implicated in the affective response to noxious somatic (41) and visceral (42,43) stimuli, and gastric mechanical distention was shown to produce activation in the brainstem in the same region (44), reflecting a modulatory activity on autonomic responses (45). Moreover, the hypothalamus, the main area of the brain that controls the autonomic system, has been suggested as a potential area of the brain that triggers migraine (46).

Another theory for the pathophysiology of migraine gave importance to a neurogenic inflammation, secondary to the release of potent vasoactive neuropeptides from the trigeminal nerve fibres during the pain phase of migraine, such as calcitonin gene-related peptide, resulting in a sterile inflammation and dilation of vessels. This trigeminovascular inflammation may be a self-perpetuating vicious circle causing painful perception (47). In this light, it is worth noting that calcitonin gene-related peptide is an important neurotransmitter for sensorimotor gastrointestinal activity.

In conclusion, our data suggest a possible link between dyspeptic symptoms and migraine, in particular when postprandial occurrence of symptoms is evident. Further studies are needed to better explain the common neurological pathway for the trigger of migraine when postprandial gastric hypersensitivity is present.

Key findings

Migraine is frequently associated with functional dyspepsia.

PDS patients, but not EPS patients, frequently show a meal-induced migraine.

Postprandial migraine is correlated with modification of the gastric discomfort threshold and its treatment should also be addressed to the improvement of visceral hypersensitivity.

Footnotes

Author contributions

Michele Di Stefano planned and conducted the study, interpreted data and drafted the manuscript. He is also is the guarantor of the article.

Ennio Pucci planned and conducted the study, collected and interpreted data and drafted the manuscript.

Emanuela Miceli conducted the study, collected and interpreted data and drafted the manuscript.

Elisabetta Pagani conducted the study, collected data and drafted the manuscript.

Giuseppe Nappi planned the study and drafted the manuscript.

Natascia Brondino conducted the study, collected data and drafted the manuscript.

Gino Roberto Corazza planned the study and drafted the manuscript.

Antonio Di Sabatino planned the study and drafted the manuscript.

Declaration of conflicting interests

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

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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Prevalence and pathophysiology of post-prandial migraine in patients with functional dyspepsia

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Patients and methods

Patients

Design of the study

Barostat test

Gastric emptying study

Symptom evaluation

Statistical analysis

Results

Prevalence of migraine

Migraine without aura and dyspeptic symptoms

Gastric sensitivity thresholds

Gastric emptying time for solids

Gastric accommodation to meal

Discussion

Key findings

Footnotes

Author contributions

Declaration of conflicting interests

Funding

References