Migraine Sufferers Research Articles

Triggers of Motion Sickness in Migraine Sufferers

To determine whether susceptibility to motion sickness provoked by unexpected movement is associated with susceptibility to visually induced motion sickness in migraine sufferers. Migraine sufferers are unusually susceptible to motion sickness, but the mechanism of this susceptibility is not well understood. Possibilities include vestibular dysfunction secondary to vasomotor disturbances during migraine attacks, hyperexcitability of brainstem circuits that produce symptoms of motion sickness and migraine, and heightened susceptibility to visual illusions of movement. A motion sickness susceptibility questionnaire that listed common triggers of motion sickness was filled out by 42 migraine sufferers and 39 headache-free controls of similar age and sex distribution to migraine sufferers. A greater proportion of migraine sufferers than controls reported that traveling in cars and buses, reading in the car, using playground equipment, watching wide-screen movies and movement simulators, induced motion sickness. However, visually induced motion sickness appeared to be independent of motion sickness to most movement-related stimuli in migraine sufferers. The lack of association between susceptibility to movement-induced and visually induced motion sickness implies that more than one mechanism increases susceptibility to motion sickness in migraine sufferers.

Comorbidity of migraine

Comorbidity refers to the greater than coincidental association of separate conditions in the same individuals. Historically, a number of conditions have been noted to be comorbid with migraine, notably psychiatric disorders (anxiety, depression, panic disorder), epilepsy, asthma, and some congenital heart defects. Migraine sufferers have increased medical costs overall compared with others of the same sex and age, even after considering the cost of specific migraine treatment. Thus, estimates of the burden of migraine often include the costs of conditions comorbid with it. Conditions may be comorbid through a variety of mechanisms. Comorbidity may be an artifact of diagnostic uncertainty when symptom profiles overlap or when diagnosis is not based on objective markers. Comorbidity may arise due to unidirectional causality, such as migraine resulting in blood pressure changes due to headache-specific treatment. Finally, conditions may be comorbid because of shared genetic or other factors that increase the risk of both conditions. In such cases, understanding these shared risk factors may lead to greater understanding of the fundamental mechanisms of migraine. In this article, we will review recent developments related to migraine comorbidity. We will emphasize findings related to the comorbidity of migraine with clinical and sub-clinical vascular brain lesions, congenital heart defects, coronary heart disease, psychiatric illness, and other pain conditions.

The Treatment of Pediatric Migraine

The management of pediatric migraine requires a balance of biobehavioral measures coupled with agents for acute treatment and, if needed, daily preventive medicines. A recent American Academy of Neurology practice parameter has critically reviewed the limited data regarding the efficacy and safety of medicines for the acute and preventive therapy of pediatric migraine. The first step is to establish the headache frequency and degree to which the migraines impact upon lifestyle and performance. The next step is to institute nonpharmacologic measures such as regulation of sleep (improved sleep hygiene), moderation of caffeine, regular exercise, and identification of provocative influences (eg, stress, foods, social pressures). A wide variety of therapeutic options exist for patients whose migraine headaches occur with sufficient frequency and severity to produce functional impairment. The most rigorously studied agents for the acute treatment of migraine are ibuprofen, acetaminophen, and sumatriptan nasal spray, all of which have shown safety and efficacy in controlled trials. Daily preventive drug therapies are warranted in about 20% to 30% of young migraine sufferers. The particular drug selected for the individual patient requires an appreciation of comorbidities such as affective or anxiety disorders, co-existent medical conditions such as asthma or diabetes, and acceptability of potential toxicities such as weight gain, sedation, or tremor.

Non-oral formulations of triptans and their use in acute migraine

The introduction of triptans (5-HT (1B/1D) agonists) into clinical practice has expanded the therapeutic options for doctors treating migraine sufferers. The triptans are available in several different formulations such as conventional oral tablets, orally disintegrating wafers, subcutaneous injections, nasal sprays, and suppositories, which provide an excellent opportunity to tailor therapy to individual patients' needs. Although the oral formulations are the most popular with patients, they are not the most appropriate route of administration for drug delivery during the migraine attack. Due to gastrointestinal dysmotility, the intestinal absorption of any triptan administered orally may be impaired and treatment effects become inconsistent. For this reason, triptans preferably should be prescribed in a non-oral formulation (injection, nasal spray, or suppository). Parenteral administration of a triptan is more likely to provide relief of symptoms, even when it is used later in the course of the migraine attack.

Neuropsychology of migraine: present status and future directions

Migraine is recognized as a primarily neural condition. Changes in neural physiology have been consistently identified in migraineurs. Numerous studies are available that evaluate physical and functional differences between migraineurs and headache-free controls. The most prominent neuroimaging findings reported in migraine sufferers have been white matter changes. However, physical changes on neuroimaging have not been clearly correlated with functional impairment in migraineurs. The current literature addressing the neuropsychologic consequences of migraine has been far from conclusive, and reports of cognitive testing in adult migraineurs and controls has yielded inconsistent results. Neuropsychologic testing suggests that there may be some subtle but possibly significant changes in cognition that occur both during and between migraine episodes. A finding emerging with some consistency is that migraine patients with aura experience more neuropsychologic deficits than migraine patients without aura. The few studies that assess nonmigraine headache suggest that physical changes may not be unique to migraine, although neuropsychologic changes do appear to be limited to migraineurs. An examination of the unmet needs and priorities for future research addressing this important topic is provided.

Migraine: barriers for care

Migraine headaches affect 12% of the adult population in occidental countries and cause a significant economic loss due to decreased workplace productivity. However only a minority of migraine sufferers worldwide ever receive a correct diagnosis or appropriate treatment. Several barriers for adequate care contribute to this situation. In this article we discuss some strategies to bypass these barriers, summarised herein as: (1) identifying migraine sufferers in need of care; (2) improving medical recognition; (3) supporting the differential diagnosis; (4) improving medical confidence; (5) improving medical treatment; and (6) assessing treatment outcomes.

Time‐Series Features of Headache: Individual Distributions, Patterns, and Predictability of Pain

This preliminary study employed "within-patient" time-series methodology to examine headache symptom distributions (peak, sum) to assess predictability of day-to-day headache based on overall pattern, and to better characterize distributional properties of headache as they relate to study design and statistics in future research. Headache symptoms for a given patient may vary widely from one day to the next, ranging from days when the headache sufferer is asymptomatic to days when he or she is functionally disabled with severe headache. Although day-to-day variations are well recognized and appreciated clinically, headache is seldom studied using daily (eg, time-series) methodology that can elucidate potentially important individual and temporal variations. Instead, most headache research has relied upon cross-sectional designs aimed at examining group rather than individual effects which may serve to mask important individual differences. Additional within-patient time-series studies are needed to help identify symptom patterns, clinically meaningful patient subgroups, and relationships among precipitants, interventions, and outcomes. Such research would be aided by delineation of the distributional and temporal properties of key scales (eg, daily headache peak, sum). The present research provides such information derived from clinical samples of migraine and tension-type headache sufferers, laying a foundation for future time-series research. Twenty-five migraine and 24 tension-type headache sufferers prospectively recorded daily headache activity for 1 month. Individual headache distributions were generated and examined individually and by diagnostic group. Predictability for headache was analyzed case by case and summarized by diagnostic group. The study determined the degree to which individual patients' headache activity distributions deviate from normality (skewness, kurtosis). For migraine and tension-type headache, individual patients' headache patterns were distinctly bimodal in nature. Notably, headache patterns with the lowest frequency were the most bimodal, and as frequency increased, the distributions tended to more closely approximate normal. Patterns were also detailed according to measures of predictability for headache (trends, autocorrelation). Generally, headache days tended to cluster together for both tension-type and migraine (positive autocorrelation) with headache on day 1 being a good predictor of headache on day 2. To the authors' knowledge, this is the first study to utilize time-series methodology to characterize individual patients' headache distributions and temporal patterns and to empirically address predictability in this manner. The bimodal distributions noted among less frequent headache patterns would suggest that basic assumptions underlying the use of inferential statistics may be violated when examining intra-individual relationships. Time-series research promises to yield unique insights into patterns, precipitants, and impact of headache disorders, but future research must address both the large degree of individual differences in headache and the account for the unique types of statistical distributions among individual headache sufferers.

The pupillary light reflex in migraine

The literature suggests that there may be pupil size and response abnormalities in migraine headache sufferers. We used an infra-red pupillometer to measure dynamic pupil responses to light in 20 migraine sufferers (during non-headache periods) and 16 non-migraine age and gender matched controls. There was a significant increase in the absolute inter-ocular difference of the latency of the pupil light response in the migraine group compared with the controls (0.062 s vs 0.025 s, p = 0.014). There was also a significant correlation between anisocoria and lateralisation of headache such that migraine sufferers with a habitual head pain side have more anisocoria (r = 0.59, p < 0.01), but this was not related to headache laterality. The pupil changes were not correlated with the interval since the last migraine headache, the severity of migraine headache or the number of migraine headaches per annum. We conclude that subtle sympathetic and parasympathetic pupil abnormalities persist in the inter-ictal phase of migraine.

Frequency Doubling Technology perimetry and standard automated perimetry in migraine

The literature suggests that visual field defects may be more common in people who experience migraine. The Humphrey frequency doubling (FDT) visual field instrument selectively examines the magnocellular visual pathway, but has not previously been used to investigate visual function in migraine. In a masked controlled study we compared Humphrey FDT and Humphrey Swedish Interactive Threshold Algorithm fields of 25 migraine sufferers with 25 age- and gender-matched controls. Although both mean deviation and pattern standard deviation were a little worse in the migraine group, these differences did not reach statistical significance. There were no inter-eye visual field differences in the migraine group compared with controls. Comparing the mean of all the contrast thresholds in each hemisphere, there were no more inter-hemifield visual field differences in the migraine group compared with controls. There was no significant difference between the migraine and control groups in intra-ocular pressures. The visual field parameters were not correlated with the interval since the last migraine headache, the severity of migraine headache, the duration of migraine headache or the number of migraine headaches per annum. In our data, there was no evidence of visual field deficits, a magnocellular deficit, or indications of glaucomatous pathology.

FRAMIG 2000: Medical and Therapeutic Management of Migraine in France

FRAMIG 2000 is a population-based survey of medical and therapeutic management of migraine in France. A total of 312 migraine sufferers were first identified from a representative sample of 4689 adult subjects using a validated questionnaire based on the IHS migraine diagnostic criteria and administered by telephone. Subjects were then interviewed using a branching questionnaire and a computer-assisted interview technique. Although 80% were self-aware of their migrainous state, 82% of migraine sufferers had no medical follow-up for migraine. The proportion of migraine sufferers who did not consult decreased slightly with increasing migraine-related disability (from 87% for subjects in MIDAS grade I to 68% for those in MIDAS grade IV). Migraine sufferers declared to effectively control only four attacks out of 10 after the first intake of the usual treatment. Only 6% of subjects in the survey received a prophylactic treatment for migraine whereas 22% were in MIDAS grade III or IV. These data show that the burden of migraine does not result from a deficit in diagnosis but instead from a deficit in patient information on the proper use of current effective treatments of migraine.

Aspirin Is Efficacious for the Treatment of Acute Migraine

More than 50% of migraine sufferers rely on over-the-counter medications for the treatment of migraine. Along with other over-the-counter products, aspirin is considered by the US Headache Consortium to be an option for first-line migraine treatment. This study assessed the efficacy and tolerability of aspirin versus placebo for the acute treatment of a single acute attack of migraine. This prospective, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy of a single, 1000-mg dose of aspirin for the treatment of acute moderate to severe migraine, with or without aura. Subjects recorded all study evaluations in a diary at baseline and at .5, 1, 2, 3, 4, 5, 6, and 24 hours after treatment. Pain was rated on a 4-point ordinal scale from no pain to severe pain. The primary efficacy end point was headache response at 2 hours. Secondary efficacy parameters included reduction of nausea, photophobia and phonophobia, pain intensity difference, and headache recurrence at 24 hours. Of 485 subjects enrolled, 409 took study medication and 401 treated a confirmed migraine attack (201 with aspirin and 200 with placebo). Baseline demographic and migraine characteristics were not significantly different between groups. The 2-hour headache response rate was 52% with aspirin versus 34% with placebo (P<.001). Aspirin was significantly more effective than placebo for pain reduction beginning 1 hour after dosing (P<.001) and continuing throughout the 6-hour evaluation period. Significantly (P<.05), more subjects were pain free from the 1-hour evaluation through the 6-hour evaluation. Of the aspirin-treated subjects, 20% were pain free at 2 hours versus only 6% of placebo-treated subjects. At 24 hours, the headache recurrence rate was 21.8% for aspirin (23 of 105 subjects) and 27.7% for placebo (19 of 68 subjects). Only 34% of aspirin-treated subjects needed rescue medication at 24 hours compared with 52% of placebo-treated subjects (P<.001). Aspirin was well tolerated, and adverse events were not significantly different between groups. This study demonstrates that aspirin is safe and effective for treatment of acute migraine in appropriately selected patients.

Painful Stimulation of the Temple During Optokinetic Stimulation Triggers Migraine-Like Attacks in Migraine Sufferers

To determine whether motion sickness induced by optokinetic stimulation would trigger migraine-like attacks, 27 migraine sufferers and 23 controls attended the laboratory up to three times at intervals of at least 3 weeks. On one occasion subjects experienced up to 15 min of optokinetic stimulation, followed by three 30-s applications of ice to the temple at 4-min intervals. On another occasion, the ice applications preceded and accompanied optokinetic stimulation. On a third occasion, one hand was immersed in ice water for 30 s, three times at 4-min intervals before and during optokinetic stimulation. Subjects recorded headache activity in a diary over the course of the study. None of the controls experienced a migraine-like attack at any stage of the experiment. In migraine sufferers, the incidence of migraine-like attacks was greater than the expected daily incidence of 8% after sessions that involved painful stimulation of the temple during or after optokinetic stimulation (44% and 28% of the group, respectively) (P<0.001). In contrast, migraine-like attacks developed in only 13% of migraine sufferers after the session that involved immersing the hand in ice water during optokinetic stimulation (not significant). The development of nausea and headache during optokinetic stimulation increased the likelihood of migraine-like attacks afterwards. These findings indicate that motion sickness and head pain increase susceptibility to migrainous attacks in migraine sufferers, and suggest that the symptoms of migraine build upon each other in a vicious circle. Thus, targeting multiple symptoms should be more effective than targeting individual symptoms, both for preventing and treating attacks of migraine.

Recognition and Management of Migraine in Primary Care: Influence of Functional Impact Measured by the Headache Impact Test (HIT)

The objective of the present study was to investigate the influence of headache-related disability on the recognition and management of migraine by French general practitioners (GPs). Forty-nine teaching GPs at the Faculty of Medicine in the Nice-Sophia-Antipolis University were involved in this study. On one day, each patient who presented during the surgery hours of these GPs was invited to complete a questionnaire aimed at identifying if he/she was a headache sufferer and, if so, whether the headache corresponded to migraine and had an impact on his/her functional ability. Functional disability was measured by the short-form of the Headache Impact Test (HIT-6). Being blind to the patients' responses, the GPs completed a questionnaire for each patient aimed at identifying if he/she considered the patient to suffer from migraine and, if so, whether he/she managed the patient for migraine. A total of 696 patients were included in this study and 289 (41.52%) of them had episodic headache. According to the new International Headache Society (IHS) criteria, 113 (16.24%) patients suffered from headache without migrainous features and 176 (25.29%) patients were migraine sufferers (migraine according to IHS categories 1.1 and 1.2.1: 11.21%, and probable migraine according to IHS categories 1.6.1 and 1.6.2: 14.08%). The mean HIT score of these migraine sufferers was 59.1+/-8.8 and 50% of them presented with a very severe impact score (HIT score>60). Among the 176 migraine sufferers, 105 (59.7%) were not recognized as having migraine, 21 (11.9%) were recognized as having migraine but without migraine management and 50 (28.4%) were recognized as having migraine with migraine management. Recognition of migraine by GPs was statistically associated with the HIT score (OR=1.105, 95% CI: 1.056-1.157, P<0.001) and with the 1.1 and 1.2.1 IHS diagnostic categories (OR=2.942, 95% CI: 1.286-5.025, P=0.0107) whereas management of patients recognized as having migraine was only associated with the patient's age (OR=1.051, 95% CI: 1.000-1.104, P=0.0486). These results indicate that the continuing medical education of GPs should focus on the diagnosis of migraine and its impact on the lifestyle of the patient.

Headaches in Women Undergoing in Vitro Fertilization and Embryo‐Transfer Treatment

In vitro fertilization and embryo transfer has become a common therapeutic modality in modern fertility medicines. Treatment protocols are associated with exaggerated hormonal fluctuations in order to promote multiple follicular development and support of embryo survival. Estrogen is considered to be closely linked to migraine, and its extreme serum level fluctuations have been considered to trigger migrainous headaches. To assess the prevalence, nature, and timing of headache attacks during the course of in vitro fertilization and embryo-transfer treatments. We retrospectively evaluated the prevalence and the characteristics of headache among 98 women undergoing in vitro fertilization and embryo transfer therapy using a structured telephone interview. Out of the 98 evaluated patients 25 were migraine sufferers. Headache attacks during the in vitro fertilization and embryo transfer protocol were reported by 28.6% (n = 28) of the women and were significantly more prevalent among the migraineurs. The attacks were of debilitating severity in 82% (n = 23) of patients who reported headaches during treatment. Headache occurred most frequently following gonadotropin-releasing hormone (GnRH) analog induced hypothalamic-pituitary-ovarian axis downregulation, typically associated with very low 17-beta-estradiol (17-beta-E2) serum level. In vitro fertilization and embryo-transfer treatment might be associated with various degrees of headache. This is mostly observed in patients with migraine headache background and specifically during the downregulation stage of treatment, when very low levels of 17-beta-E2 are observed. (Headache 2005;45:215-219).

Psychiatric Comorbidity in Migraine: A Review

Investigations of migraine comorbidity have confirmed its association with diverse psychiatric conditions. This association appears to be strongest for major depression and anxiety disorders (particularly panic and phobia), but increased comorbidity has also been reported with substance abuse and certain mood disorders. This literature also indicates that greater psychiatric comorbidity exists for migraine sufferers with aura than without. Some support is found for the notion that psychiatric comorbidity is higher in transformed migraine than in simple migraine (particularly in the case of chronic substance abuse). However, research into the possible mechanisms underlying these associations remains limited. Studies examining the order of onset and the cross-transmission of migraine and psychiatric disorders in families have been unable to distinguish fully between causal and common aetiological models of association. The conclusions are discussed in light of both methodological and conceptual issues relevant to understanding migraine comorbidity.

How treatment priorities influence triptan preferences in clinical practice: perspectives of migraine sufferers, neurologists, and primary care physicians

ABSTRACTBackground: In treating migraine sufferers, physicians can choose from among seven triptans with different attributes.Objective: To develop a system for selecting an oral triptan based on treatment priorities of migraine sufferers, neurologists, and primary care physicians (PCPs) in the United States, and evidence-based performance of triptans in clinical trials.Methods: The TRIPSTAR project combines data on the treatment preferences of migraineurs and physicians with results from a meta-analysis of individual triptans, which evaluated their effectiveness on various clinical endpoints. Telephone interviews with migraine sufferers, neurologists, and PCPs were conducted to elicit individual views on the relative importance of a prespecified set of acute treatment outcomes. Four hundred and fifteen migraine sufferers, both triptan-experienced and triptan-naive, were interviewed. Also, 200 board-certified neurologists and 200 PCPs provided information on migraine patients from their clinical practice. A multi-attribute decision model for selecting an oral triptan was constructed using attribute importance weights collected at telephone interview and the meta-analysis data, which were drawn from 53 clinical trials of 6 oral triptans.Results: Efficacy attributes were rated significantly more important than tolerability or consistency in selecting an oral triptan, according to migraine sufferers and physicians. Freedom from cardiovascular adverse events was the most important tolerability attribute, according to migraine sufferers and physicians alike. Pain free at 1 h was the most important lower-level efficacy attribute for migraine sufferers, while sustained pain free was most important for physicians. When weighted treatment attributes were combined with meta-analysis data in a multi-attribute decision model, almotriptan 12.5 mg, eletriptan 80 mg, and rizatriptan 10 mg were significantly closer to the hypothetical ideal triptan than was sumatriptan 100 mg. Triptans selected by the model were generally closer to the patient-specific ideal triptan than were the triptans prescribed by physicians.Conclusions: Almotriptan, eletriptan, and rizatriptan were the three triptans closest to the ideal, from the perspectives of migraine sufferers, PCPs, and neurologists alike. The TRIPSTAR model may be a potentially useful decision-support tool to help physicians select the triptan most likely to produce a successful outcome in migraine sufferers.

An Assessment of the Burden of Migraine using the Willingness to Pay Model

Willingness to pay methods measure treatment preferences and also measure the burden of illness in economic terms. We used a contingent valuation method to measure migraine sufferers' willingness to pay (WTP) for acute medication for their most severe headache attacks, based on various profiles of treatment benefits and the characteristics of the migraine sufferer. Subjects were identified from a population-based database of migraine sufferers, previously recruited by random digit dialing. Telephone interviews (n = 1428) were used to gather demographic and headache characteristics. Subjects who met the International Headache Society criteria for migraine with or without aura and satisfied the other inclusion criteria based on telephone interview (n = 312) were invited to participate in a mailed questionnaire study. The questionnaire was mailed to the 310 subjects who agreed to participate and 201 (65%) surveys were returned. The survey included questions on the demographics, the migraine characteristics, and the psychological disposition of the respondents. WTP for an acute migraine treatment with 14 different hypothetical treatment profiles was explored. Responders and non-responders to the survey were generally similar. The newly designed WTP questionnaire had high internal consistency (Cronbach's alpha 0.90) and test-retest reliability (Spearman's correlation coefficients 0.71-0.77). Study subjects were willing to pay a median price of US 5 dollars for a migraine treatment that provided complete relief in 30 min and worked 100% of the time, with no side-effects and no headache recurrence. Median WTP decreased as treatment attributes deviated from this ideal. For example, WTP declined to a median of US 1 dollar for complete relief in 2 h and to US 0.25 dollars for complete relief in 4 h. All of the medication attributes powerfully influenced WTP. Several variables predicted WTP including current payment for medication, MIDAS (Grade III), and those with headaches of long duration. Subjects who employed a greater number of coping skills were less willing to pay. Patient demographics and migraine severity predict WTP, but treatment attributes were also important. As treatment improves, WTP for migraine medications is likely to increase.

Passive Infrared Hemoencephalography: Four Years and 100 Migraines

Background. One hundred migraine sufferers were treated using passive Infrared Hemoencephalography (pIR HEG) over a period of four years. All subjects met the criteria for at least one of the categories set forth in the International Headache Society (IHS, 1988) classification criteria for headache disorders for primary migraine. Methods. Subjects were treated using the pIR HEG system in 30-minute sessions. A central forehead placement (approximately Fpz) was used for the sensor assembly for all subjects. Changes in headache patterns were examined. After two years, an infrared video imaging system was added to the data collection process and was available for 61 of the 100 subjects. Infrared forehead images were captured at the start and end of each session to examine changes in prefrontal cortical brain activity. Results. Most of the subjects improved control over their migraine headaches. Over 90% of those subjects who completed at least six sessions reported significant improvements in migraine activity. Conclusions. pIR HEG appears to have a strong impact on migraine headaches, even for peoplewho have not had a positive response to medication. Headache response by the end of six sessions appears to be a good predictor of probability of improvement.

Are migraineurs hypersensitive? A test of the stimulus processing disorder hypothesis

The concept of hypersensitivity in migraineurs was advanced mainly on the basis of studies on information processing in which increased amplitudes and reduced habituation in cortical evoked and event related potentials were found in migraine sufferers. The present investigation examined whether migraineurs exhibit hypersensitivity within three different experimental paradigms and various non electrocortical response parameters. Samples of 24 migraine, 19 tension-type headache sufferers, and 24 normal controls were compared regarding their subjective estimation of intensity and discomfort due to visual and acoustical stimuli. Subjects also participated in an experiment using the eyeblink startle response paradigm. In a last experimental task the Stroop test was applied. The trait variables emotionality, arousal, and extraversion were also measured. None of the experimental tasks revealed the predicted hypersensitivity of migraineurs in relation to the control samples. The series of experiments was conducted a second time with half of the participants in order to replicate the findings. The conclusions remained the same. The results of earlier studies on cortical processing can not be interpreted as demonstrating general hypersensitivity in the sense of a dispositional trait in migraine afflicted individuals irrespective of the involved response system.

Painful Stimulation of the Temple Induces Nausea, Headache and Extracranial Vasodilation in Migraine Sufferers

To determine whether painful stimulation of the temple would induce nausea, ice was applied to the temple for 30 s, three times at 4-min intervals in 23 migraine sufferers and 22 age- and sex-matched controls. On one occasion, the ice was applied in the presence of residual motion sickness induced by optokinetic stimulation. On another occasion, the ice application was not preceded by optokinetic stimulation (the baseline condition). In the baseline condition, nausea had developed in migraine sufferers but not controls by the third application of ice. In the presence of residual motion sickness, each painful stimulus intensified nausea and headache in migraine sufferers whereas symptoms were minimal in controls. Changes in frontotemporal pulse amplitude were monitored with photoelectric pulse transducers. The extracranial blood vessels dilated in migraine sufferers but not controls before the first application of ice in the baseline condition, presumably due to anticipatory anxiety. In contrast, the ice application did not provoke extracranial vasodilation in either group after optokinetic stimulation. The findings show that susceptibility to nausea and stress-induced extracranial vascular hyper-reactivity are associated with the migraine predisposition. They also suggest that head pain might intensify gastrointestinal disturbances during attacks of migraine.