Showing papers in "Headache in 2006"

Patterns of diagnosis and acute and preventive treatment for migraine in the United States: results from the American Migraine Prevalence and Prevention study.

Abstract: Objective.—To describe the patterns of medical treatment for migraineurs in the United States. Background.—Over the past decade, many new treatments for migraine have become available and awareness of migraine has improved. However, there is little information about the patterns of medical treatment in the US society. Design/Methods.—A validated self-administered headache questionnaire was mailed to a random sample of 120,000 US households. Each household member with severe headaches was asked to complete the survey. The questionnaire assessed headache features, disability, and patterns of medical treatment. Subjects were classified according to their use of headache preventive medication, as current users, coincident users (using effective medications for other medical reasons), lapsed users (had used in the past but not at the time of the survey), or never users. Results.—In 162,576 participants, the prevalence of migraine was 17.1% in women and 5.6% in men. Only 56.2% of those with migraine had ever received a medical diagnosis. Ninety-eight percent of the migraineurs used acute treatment for their migraine attacks. Forty-nine percent (49%) usually used over-the-counters, 20% usually used prescription medications, and 29% used both. Only 12.4% of migraineurs indicated that they were taking a migraine preventive medication, but 17.2% were using medications with potential antimigraine effects for other medical reasons. Current or past use of preventive medication was more likely in women than men (odds ratio [OR]= 1.37, 95% confidence interval [CI] 1.27-1.48), increased with age and individuals with high MIDAS grade (Grade IV vs I, OR 2.35, 95% CI 2.09-2.64). Preventive medication use increased with awareness of migraine and with illness severity. Conclusions.—Migraine remains undertreated in the US population. Barriers to preventive treatment are greater in younger age groups, men, and people unaware that they have migraine.

Psychiatric Comorbidity of Migraine

Abstract: Migraine affects nearly 12% of the adult population in the United States and causes significant lost productivity and decrements in health-related quality of life. The burden of migraine and the challenge in managing it are increased by the comorbid psychiatric conditions that occur in association with it. Studies in both clinical and community-based settings have demonstrated an association between migraine and a number of specific psychiatric disorders. This review will focus on the relationships between migraine and depression, generalized anxiety disorder, panic disorder, and bipolar disorder. In large scale population-based studies, persons with migraine are from 2.2 to 4.0 times more likely to have depression. In longitudinal studies, the evidence supports a bidirectional relationship between migraine and depression, with each disorder increasing the risk of the other disorder. Migraine is also comorbid with generalized anxiety disorder (Odds Ratio [OR] 3.5 to 5.3), panic disorder (OR 3.7), and bipolar disorder (OR 2.9 to 7.3). A diagnosis of migraine should lead to a heightened level of diagnostic suspicion for these comorbid psychiatric disorders. Similarly, a diagnosis of one of these psychiatric disorders should increase vigilance for migraine. Treatment plans for migraine should be mindful of the comorbid conditions.

Modifiable risk factors for migraine progression.

Abstract: Migraine is a chronic-recurrent disorder that progresses in some individuals. Transformed migraine is the result of this progression. Since migraine does not progress in most patients, identifying the risk factors for progression has emerged as a very important public health priority. If risk factors can be identified, that might provide a foundation for more aggressive preventive intervention. Risk factors for progression may be divided into non-remediable (gender, age, race) and remediable categories. In this paper, we focus on several already identified remediable risk factors, including frequency of migraine attacks, obesity, acute medication overuse, caffeine overuse, stressful life events, depression, and sleep disorders. We present the evidence for each risk factor and discuss possible interventions to address them.

Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part 2.

Abstract: Ovarian hormones have a significant effect on the central nervous system of female migraineurs. Reproductive milestones such as menarche, pregnancy, and menopause are associated with changes in the clinical course of migraine headache. Migraine attacks are commonly triggered during declines in serum estrogen levels that occur before and during the time of menstruation. Therefore, substantial clinical evidence suggests that changes in ovarian hormones affect migraine headache. This represents the first of two manuscripts defining the role of ovarian hormones in the pathogenesis of migraine headache. The purpose of the first article will be to review the molecular and neurophysiologic effects of estrogen and progesterone on neurotransmitter systems and pain processing networks relevant to migraine headache. The second manuscript will focus on the clinical studies detailing the influence of estrogen and progesterone on migraine headache.

Calcitonin Gene‐Related Peptide (CGRP) and Migraine

Abstract: The neuropeptide calcitonin gene-related peptide (CGRP) has long been postulated to play an integral role in the pathophysiology of migraine. While clinical findings are consistent with such a role, the specific pathogenic mechanisms of CGRP in migraine have remained speculative until recently. Through advances in molecular neuroscience, the pathogenic mechanisms of CGRP in migraine have begun to be elucidated. This paper discusses the hypothesized role of CGRP in migraine and reviews recent findings on the molecular mechanisms of this neuropeptide in migraine pathophysiology. Studies in cultured trigeminal neurons demonstrate that CGRP is released from trigeminal ganglia cells, that CGRP transcription is increased under conditions mimicking neurogenic inflammation, that migraine pharmacotherapies can both reduce CGRP release and inhibit CGRP transcription, and that tumor necrosis factor-α (TNF-α), an endogenous inflammatory mediator implicated in migraine, can stimulate CGRP transcription. Together, the results suggest that, in migraine, activation of trigeminal nerves release CGRP and other peptides that cause the release of proinflammatory mediators. These mediators further increase CGRP synthesis and release over hours to days in correspondence with the 4- to 72-hour duration of a typical migraine episode. The increased CGRP synthesis and release might be mediated by activation of mitogen-activated protein kinase pathways, which, in turn, can be modulated by endogenous inflammatory substances such as TNF-α and affected by drugs such as sumatriptan.

Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally.

Abstract: Objective.—The aim of the present research was to verify the levels of the soluble adhesion molecules sL- and sE-selectins, intercellular adhesion molecule (sICAM)-1, and vascular cell adhesion molecule-1 in serial samples of internal jugular venous blood taken from migraine patients without aura (MWoA) during attacks. The expression of leukocyte function antigen (LFA)-1 and very late activation antigen (VLA)-4 was also assessed on lymphocytes obtained from jugular venous blood. Levels of certain proinflammatory cytokines (tumor necrosis factor-α[TNF-α], interleukin-1β[IL-1β], IL-4, and IL-6) were also determined and correlated with those of adhesion molecules. Patients and Methods.—Seven MWoA patients were admitted in the hospital during attacks and blood samples were taken immediately after catheter insertion, at 1, 2, and 4 hours after attack onset, and within 2 hours after its termination. The levels of adhesion molecules and cytokines were measured with ELISA method. The expression of LFA-1 and VLA-4 was assessed by flow cytometry. Results.—A parallel transient increase of sICAM-1, TNF-α, and IL-6 was observed in the first 2 hours after attack onset compared with the time of catheter insertion (P < .0001, <.001, and <.003, respectively). The proportion of CD4+ and CD8+ T-cells expressing high levels of LFA-1 showed instead a progressive down-regulation with significantly lower percentages at 2 and 4 hours after attack onset (P < .01 and <.022, respectively). No variation in the percentage of VLA-4 expressing cells was observed at any time of the study. Conclusions.—The transient increase in sICAM-1 and TNF-α found in the internal jugular blood of MWoA patients assessed ictally can be induced by sensory neuropeptides released from activated trigeminal endings. The progressive decrease in sICAM-1 levels during attacks and the down-regulation of LFA-1 expression by lymphocytes could antagonize their transvascular migration, supporting the hypothesis of sterile inflammation in the dura mater during migraine attacks.

Central sensitization theory of migraine: Clinical implications

Abstract: The clinical science of migraine headache continues to evolve. Theories of the pathophysiology of migraine have progressed from the early vascular basis of migraine to more complex current theories that emphasize the centrality of neuronal dysfunction. The most recently articulated theory of migraine is the central sensitization hypothesis, which proposes that altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis, could account for many of the temporal and symptomatic features of migraine, as well as its poor response to triptan therapy when such treatment is initiated hours after the onset of pain. Both preclinical and clinical data support the central sensitization theory. A critical clinical implication of this theory is that drugs that are capable of either aborting or arresting the process of central sensitization, most prominently dihydroergotamine, may have a unique role in the treatment of migraine. An additional, and highly practical, implication is based upon the finding that cutaneous allodynia-pain arising from innocuous stimulation of the skin, as in hair brushing or the application of cosmetics-is an easily identifiable marker of central sensitization. Thus, the presence or absence of cutaneous allodynia can be integrated into the routine clinical assessment of migraine and utilized as a determinant of treatment. Future basic and clinical research on central sensitization is likely to be of ongoing importance to the field.

Trigger points in the suboccipital muscles and forward head posture in tension-type headache.

Abstract: Objective—To assess the presence of trigger points (TrPs) in the suboccipital muscles and forward head posture (FHP) in subjects with chronic tension-type headache (CTTH) and in healthy subjects, and to evaluate the relationship of TrPs and FHP with headache intensity, duration, and frequency Background—Tension-type headache (TTH) is a prototypical headache in which myofascial TrPs in the cervical and pericranial musculature can play an important role Design—A blinded, controlled pilot study Methods—Twenty CTTH subjects and 20 matched controls without headache participated TrPs were identified by eliciting referred pain with palpation, and increased referred pain with muscle contraction Side-view pictures of each subject were taken in sitting and standing positions, in order to assess FHP by measuring the craniovertebral angle Both measures were taken by a blinded assessor A headache diary was kept for 4 weeks in order to assess headache intensity, frequency, and duration Results—Sixty-five percent (13/20) CTTH subjects showed active TrPs and 35% (7/20) had latent TrPs in the suboccipital muscles Six (30%) controls also had latent TrPs Differences in the presence of suboccipital muscle TrPs between both the groups were significant for active TrPs (P 5) CTTH subjects with active TrPs reported a greater headache intensity and frequency than those with latent TrPs (P < 05) The degree of FHP was greater in CTTH subjects than in controls in both sitting and standing positions (P < 01) Within the CTTH group, there was a negative correlation between the craniovertebral angle and the frequency of headache (rs=−06, P < 01, in sitting position; rs=−05, P < 05, in standing position) CTTH subjects with active TrPs had a greater FHP than those with latent TrPs, though this difference was not significant Conclusions—Suboccipital active TrPs and FHP were associated with CTTH CCTH subjects with active TrPs reported a greater headache intensity and frequency than those with latent TrPs The degree of FHP correlated positively with headache duration, headache frequency, and the presence of suboccipital active TrPs

Myofascial trigger points and their relationship to headache clinical parameters in chronic tension-type headache.

Abstract: Objective.—To assess the presence of trigger points (TrPs) in several head and neck muscles in subjects with chronic tension-type headache (CTTH) and in healthy subjects; and to evaluate the relationship of these TrPs with forward head posture (FHP), headache intensity, duration, and frequency. Background.—Tension-type headache (TTH) is a headache in which myofascial TrPs in head and neck muscles might play an important etiologic role. Design.—A blinded, controlled, pilot study. Methods.—Twenty-five CTTH subjects and 25 matched controls without headache were studied. TrPs in bilateral upper trapezius, sternocleidomastoids, and temporalis muscles were identified according to Simons et al's diagnostic criteria: tenderness in a hyperirritable spot within a palpable taut band, local twitch response elicited by snapping palpation, and elicited referred pain with palpation. A TrP was considered active if the subject recognized the evoked referred pain as familiar headache. If the evoked referred pain was not recognized as familiar headache, the TrP was considered as latent. Side-view pictures of each subject were taken in both sitting and standing positions in order to assess FHP by measuring the cranio-vertebral angle. Both measurements were made by a blinded assessor. A headache diary was kept for 4 weeks in order to assess headache intensity, frequency, and duration. Results.—The mean number of TrPs on each CTTH subject was 3.9 (SD: 1.2), of which 1.9 (SD: 1.2) were active TrPs and 1.9 (SD: 0.8) were latent TrPs. Control subjects only exhibited latent TrPs (mean: 1.4; SD: 0.8). There was a significant difference between the CTTH group and the controls for active TrPs (P .05). Differences in the distribution of active and latent TrPs within each muscle were also significant for all the analyzed muscles (P < .01). CTTH subjects with active TrPs in the right upper trapezius muscle or left sternocleidomastoid muscle showed a greater headache intensity and duration, but not headache frequency, compared to those with latent TrPs (P < .05). Active TrPs in the right temporalis muscle were associated with longer headache duration (P < .01), whereas active TrPs in the left temporalis muscle were associated with greater headache intensity (P < .05). CTTH subjects with active TrPs in the analyzed muscles had a greater FHP than those with latent TrPs in both sitting and standing positions. Differences were only significant for TrPs in the left sternocleidomastoid and FHP in the sitting position (P < .01). Conclusions.—Active TrPs in upper trapezius, sternocleidomastoid, and temporalis muscles were associated with CTTH. CTTH subjects with active TrPs usually reported a greater headache intensity and longer headache duration than those with latent TrPs. CTTH subjects with active TrPs tended to have a greater FHP than CTTH subjects with latent TrPs.

Understanding Psychological Stress, Its Biological Processes, and Impact on Primary Headache

Abstract: Psychological stress is generally acknowledged to be a central contributor to primary headache. Stress results from any challenge or threat, either real or perceived, to normal functioning. The stress response is the body's activation of physiological systems, namely the hypothalamic-pituitary-adrenal axis, to protect and restore functioning. Chronic activation of the stress response can lead to wear and tear that eventually can predispose an individual to disease. There are multiple ways that stress and headache are closely related. Stress can (a) be a predisposing factor that contributes to headache disorder onset, (b) accelerate the progression of the headache disorder into a chronic condition, and (c) precipitate and exacerbate individual headache episodes. How stress impacts headache is not often understood. However, stress is assumed to affect primary headache by directly impacting pain production and modulation processes at both the peripheral and central levels. Stress can also independently worsen headache-related disability and quality of life. Finally, the headache experience itself can serve as a stressor that compromises an individual's health and well-being. With the prominent role that stress plays in headache, there are implications for the evaluation of stress and the use of stress reduction strategies at the various stages of headache disorder onset and progression. Future directions can help to develop a better empirical understanding of the pattern of the stress and headache connections and the mechanisms that explain the connections. Further research can also examine the interactive effects of stress and other factors that impact headache disorder onset, course, and adjustment.

Headache and Sleep Disorders: Review and Clinical Implications for Headache Management

Abstract: Review of epidemiological and clinical studies suggests that sleep disorders are disproportionately observed in specific headache diagnoses (eg, migraine, tension-type, cluster) and other nonspecific headache patterns (ie, chronic daily headache, "awakening" or morning headache). Interestingly, the sleep disorders associated with headache are of varied types, including obstructive sleep apnea (OSA), periodic limb movement disorder, circadian rhythm disorder, insomnia, and hypersomnia. Headache, particularly morning headache and chronic headache, may be consequent to, or aggravated by, a sleep disorder, and management of the sleep disorder may improve or resolve the headache. Sleep-disordered breathing is the best example of this relationship. Insomnia is the sleep disorder most often cited by clinical headache populations. Depression and anxiety are comorbid with both headache and sleep disorders (especially insomnia) and consideration of the full headache-sleep-affective symptom constellation may yield opportunities to maximize treatment. This paper reviews the comorbidity of headache and sleep disorders (including coexisting psychiatric symptoms where available). Clinical implications for headache evaluation are presented. Sleep screening strategies conducive to headache practice are described. Consideration of the spectrum of sleep-disordered breathing is encouraged in the headache population, including awareness of potential upper airway resistance syndrome in headache patients lacking traditional risk factors for OSA. Pharmacologic and behavioral sleep regulation strategies are offered that are also compatible with treatment of primary headache.

Cluster headache: clinical presentation, lifestyle features, and medical treatment.

Abstract: Background.—Cluster headache (CH) is a rare but severe headache form with a distinct clinical presentation. Misdiagnoses and mismanagement among these patients are high. Objective.—To characterize clinical features and medical treatment in patients with CH. Methods.—We established a cohort of 246 clinic-based and non-clinic-based CH patients. The diagnosis of CH was verified according to International Headache Society (IHS) criteria. We used standardized questionnaires to assess associated factors as well as success or failure of treatments. Results.—The majority (75.6%) was not treated before at our clinic—77.6% were males; 74.8% had episodic CH, 16.7% had chronic CH, in the remaining patients, the periodicity was undetermined because they were newly diagnosed. Cranial autonomic features were present in 98.8%, nausea and vomiting in 27.8%, and photophobia or phonophobia in 61.2% of CH patients. Most (67.9%) reported restlessness during attacks and 23% a typical migrainous aura preceding the attacks. The rate of current smoking was high (65.9%). Half of the patients reported that alcohol (red wine in 70%) triggered CH attacks. Eighty-seven percent reported the use of drugs of first choice (triptans 77.6%, oxygen 71.1%) with sumatriptan subcutaneous injection being the most effective drug for acute therapy (81.2%). The most frequently used preventive medications were verapamil (70.3%) and glucocorticoids (57.7%) with equally high effectiveness. Conclusions.—Apart from the IHS criteria additional features like nausea/vomiting and migrainous aura may guide the diagnosis of CH. A large number of CH patients do not receive adequate treatments.

Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients.

Abstract: Background.—Secretion of calcitonin gene-related peptide (CGRP) from trigeminal nerves and vasoactive intestinal peptide (VIP) from parasympathetic nerves is involved in the pathophysiology of migraine and rhinosinusitis. Analysis of these neuropeptides in human saliva samples can be used as markers of trigeminal and parasympathetic nerve activity in patients between and during attacks as well as in response to specific treatments. Objective.—To compare the amount of trigeminal sensory and parasympathetic nerve activation by measuring CGRP and VIP levels in the saliva of subjects experiencing noninfectious allergic rhinosinusitis, migraine with sinus symptoms, and no symptoms. Methods.—Subjects were enrolled in three groups. Group A: subjects without a history of migraine, “sinus” headache, or allergic rhinosinusitis within the previous 6 months. Group B: subjects with chronic recurrent noninfectious rhinosinusitis and no history of migraine or “sinus” headache. Group C: subjects with self-described “sinus” headaches whose symptoms met International Headache Society diagnostic criteria (1.1 or 1.2) for migraine. The total amount of CGRP and VIP present in saliva collected under normal, pathological, and therapeutic conditions was determined by radioimmunoassay. Neuropeptide levels were normalized to total volume and amount of protein, and levels were correlated to onset and change in clinical symptoms. Results.—Total volume, total protein, and CGRP and VIP levels did not significantly change in saliva collected on consecutive days in the clinic and at the subject's home, respectively. No appreciable change in baseline salivary levels of CGRP and VIP was detected in control subjects. However, baseline salivary levels of CGRP and VIP were significantly elevated between attacks in allergic rhinosinusitis and migraine subjects compared to control values. For rhinosinusitis subjects, the amount of CGRP and VIP during attacks returned to baseline values following treatment with pseudoephedrine and relief of symptoms. Similarly, CGRP and VIP levels during a migraine headache were significantly reduced within 2 hours after sumatriptan treatment and reported symptom relief. Conclusion.—Correlation of CGRP and VIP saliva levels observed in our study supports physiologically coordinated regulation of trigeminal and parasympathetic nerve activation in allergic rhinosinusitis and migraine patients between and during attacks as well as following treatment. Furthermore, our findings demonstrate that analysis of human saliva neuropeptides may provide a semiquantitative index of pathological and therapeutic states and, therefore, function as a clinical model for studying neuronal mechanisms involved in migraine and rhinosinusitis.

Mood and Anxiety Disorders in Chronic Headache

Abstract: Although most individuals with recurrent headache disorders in the general population do not experience severe psychopathology, population-based studies and clinical investigations find high rates of comorbidity between headache and mood and anxiety disorders. When present, psychiatric disorders may complicate headache treatment and portend a poorer treatment response. The negative prognosis associated with psychiatric comorbidity emphasizes the importance of the identification of psychopathology among those with headache beginning at an early age, and suggests that the treatment of psychiatric comorbidity is warranted to improve the outcome of headache management. In this article we describe the mood and anxiety disorders most commonly associated with migraine, tension-type headache, and chronic daily headache. We provide recommendations for the assessment of comorbid mood and anxiety disorders as well as a brief overview of treatment options. Last, we discuss the clinical implications of mood and anxiety disorders on the treatment and outcome of headache.

Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study.

Abstract: Objective.—This exploratory trial evaluated the safety and efficacy of multiple treatments of botulinum toxin type A (BoNTA; BOTOX®, Allergan, Inc., Irvine, CA, USA) as prophylactic treatment of episodic migraine headaches. Design and Methods.—This was an 11-month randomized, double-blind, placebo-controlled, exploratory study. Patients were screened during a 30-day baseline period, and eligible patients with 4 or more migraine episodes and ≤15 headache days entered a single-blind 30-day placebo run-in period. Patients were classified as placebo nonresponders (PNR) if they had at least 4 moderate-to-severe migraine episodes and did not experience at least a 50% decrease from baseline in the frequency of migraine episodes following their placebo treatment. All other subjects were classified as placebo responders (PR). Patients were randomized within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA per treatment cycle) or placebo at 90-day intervals using a modified follow-the-pain treatment paradigm. The primary efficacy outcome measure was the mean change from baseline in the frequency of migraine episodes for the 30 days prior to day 180 in the PNR group. Secondary efficacy measures included the proportion of patients with a decrease from baseline of 50% or more migraine episodes per 30-day period. Patients were allowed to take concomitant acute and prophylactic headache medications. Adverse events were reported. Results.—A total of 809 patients were screened and 369 patients (89.2% female; mean age, 45 years; range, 20 to 65 years) entered the placebo run-in period and were subsequently randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U) (range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met. Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were observed (P > .999). From day 180 through the end of the study (day 270) at least 50% of all patients in each treatment group had a decrease from baseline of 50% or more migraine episodes per 30-day period. However, in the group of patients with ≥12 headache days at baseline (and ≤15 headache days), BoNTA patients experienced a mean change from baseline of −4.0 headache episodes at day 180 compared with −1.9 headache episodes in the placebo group (P= .048). The majority of treatment-related adverse events were transient and mild to moderate in severity. Only 7 patients (1.9%) discontinued the study due to adverse events (6 BoNTA, 1 placebo). Conclusion.—There were no statistically significant between-group differences in the mean change from baseline in the frequency of migraine episodes per 30-day period. There were substantial, sustained improvements during the course of the study in all groups. Multiple treatments with BoNTA were shown to be safe and well tolerated over an active treatment period lasting 9 months.

A Novel Method of Eliciting Pain-Related Potentials by Transcutaneous Electrical Stimulation

Abstract: Background.—Electrophysiological techniques such as laser and contact heat evoked pain-related potentials are very useful for studying trigeminal and somatic pain transmission in humans. These methods are, however, partly invasive, expensive, and therefore not available for broad clinical use. We recently proposed a novel technique of noninvasive transcutaneous electrical stimulation. Objective.—To elicit pain-related evoked potentials (PREP) by using a concentric planar electrode and demonstrate their nociceptive specificity. Methods.—We registered PREP following stimulation of the forehead and hand in 14 healthy volunteers. Latencies, peak-to-peak amplitudes, and conduction velocities of nociceptive fibers have been estimated. Effects of temporal and spatial summation and of cutaneous anesthesia were evaluated. Results.—Stimulation with the concentric planar electrode produced pinprick-like painful sensation. Cutaneous anesthesia led to abolishment of PREP responses. Estimated mean conduction velocity was 11.61 ± 5.12 m/s, which corresponded well with conduction via A-delta fibers. Spatial as well as temporal summation resulted in a parallel increase of perceived pain intensity and PREP amplitudes. Conclusion.—The technique is noninvasive, affordable, and easy to perform and allows quantitative assessment of human nociceptive pathways.

Headache and Psychological Functioning in Children and Adolescents

Abstract: Headache can affect all aspects of a child's functioning, leading to negative affective states (eg, anxiety, depression, anger) and increased psychosocial problems (for instance, school absences, problematic social interactions). For children and adolescents who experience frequent headache problems, comorbid psychological issues are a well-recognized, but poorly understood, clinical phenomenon. The confusion surrounding the relationship between pediatric headache and psychopathology exists for several reasons. First, in some cases, headache has been inappropriately attributed to psychological or personality features based on anecdotal observations or interpretations that go beyond the available data. Additionally, measures of psychopathology have not always adhered to the American Psychiatric Association's diagnostic criteria, thus reducing the reliability of diagnostic judgments. Furthermore, the diagnosis of headache has not always followed standard criteria, and has been complicated by the emergence of new terms and evolving measures. Finally, methodological shortcomings, such as incomplete descriptions of the procedures and criteria used for the study, inadequate descriptions of headache severity, lack of a control group for comparison with individuals without headaches, reliance primarily on cross-sectional research designs that are often discussed with inferences to causal hypotheses, and the use of unstandardized assessment measures, have significantly limited the validity of research findings. The goal of the current review is to examine the extant literature to provide the most up-to-date picture on what the research has made available about the magnitude, specificity, and causes of psychopathology in children and adolescents with headache, in an effort to further elucidate their relationship and prompt a more methodologically rigorous study of these issues.

The prevalence and impact of migraine headache in bipolar disorder: results from the Canadian Community Health Survey.

Abstract: Objective.—To report on the prevalence of comorbid migraine in bipolar disorder and the implications for bipolar age of onset, psychiatric comorbidity, illness course, functional outcome, and medical service utilization. Background.—Migraine comorbidity is differentially reported in bipolar versus unipolar depressed clinical samples. The bipolar disorder-migraine association and its consequences have been infrequently reported in epidemiological studies. Methods.—Data for this analysis were derived from respondents (n = 36 984) to the Canadian Community Health Survey – Mental Health and Well-Being (CCHS). Respondents reporting a lifetime WHO-CIDI-defined manic episode and physician-diagnosed migraine (lifetime) were compared to respondents without migraine on sociodemography, course of illness, and medical service utilization indices. Results.—An estimated 2.4% of the sample met criteria for bipolar disorder. Persons with bipolar disorder had a relatively higher prevalence of migraine versus the general population (24.8% vs. 10.3%; P < .05). The sex-specific prevalence of comorbid migraine in bipolar disorder was 14.9% for males and 34.7% for females. Bipolar males with comorbid migraine were more likely to live in a low income household (P < .05); receive welfare and social assistance (P < .05); report an earlier age of onset of bipolar disorder (P < .05); and have a higher lifetime prevalence of comorbid anxiety disorders (P < .05). Bipolar males with comorbid migraine were also more likely to utilize primary (P < .05) and mental health care services (P < .05) . Bipolar females with comorbid migraine had more comorbid medical disorders (P < .05) and were more likely to require help with personal or instrumental activities of daily living when compared to bipolar females without migraine. Conclusion.—Bipolar disorder with comorbid migraine is prevalent and associated with greater dysfunction and medical service utilization, notable in males. Opportunistic screening and surveillance for bipolar and comorbid migraine is warranted.

The impact of intensive patient education on clinical outcome in a clinic-based migraine population.

Abstract: Objective.—To determine whether the addition of patient education to routine medical management improves the clinical status of migraine patients and reduces their utilization of healthcare resources. Background.—Optimal migraine management typically requires effective patient education. Such education often is difficult to accomplish in the busy clinic setting. Methods.—One hundred consecutive patients with migraine presenting to an university-based headache clinic were randomized to receive or not receive a standardized course of didactic instruction regarding migraine biogenesis and management. The course consisted of 3 classes taught by lay migraineurs who themselves previously had undergone intensive training. All patients were evaluated initially and at 1, 3, and 6 months by a neurologist blinded as to the results of randomization. Clinical variables examined included headache frequency/severity, migraine disability assessment (MIDAS) scores, patient compliance, presence versus absence of analgesic use/overuse, and headache-related unscheduled visits or phone calls. Comparisons were made between baseline findings and findings at the 6-month follow-up visit, with the change in mean MIDAS score serving as the primary outcome variable. Results.—At 6 months the group randomized to receive intensive education exhibited a significantly greater reduction in mean MIDAS score than the group randomized to routine medical management only (24 vs. 14 points; P < .05). Those patients also experienced a reduction in mean headache days per month and a greater reduction in functionally incapacitating headache days per month, exhibited less analgesic overuse and need for abortive therapy, were more compliant with prophylactic therapy prescribed, and made fewer headache-related calls to the clinic or unscheduled visits. Conclusion.—Intensive education of migraine patients by trained lay instructors may convey significant benefit to those patients and reduce their utilization of healthcare resources.

Gastric stasis in migraine: more than just a paroxysmal abnormality during a migraine attack.

Abstract: Objective.—The aim of this article is to evaluate gastric motility and emptying in the ictal and interictal period in migraine. Background.—Nausea is a predominant symptom of migraine and the basis of it is thought to be gastric stasis. Objective methods to establish this are however lacking. We utilized gastric scintigraphy studies to determine gastric motility in the ictal and interictal period of migraine. Methods.—Ten migraine subjects were compared to equal number of age and sex matched controls. Gastric scintigraphy using a standard meal was performed in all control subjects once and in all 10 migraine subjects in the interictal period and nine studies were performed in the ictal period migraine. Results.—The time to half emptying was delayed in migraine ictally (78%) and interictal period (80%) using normative data at this institution. Gastric stasis was less pronounced ictally (149.9 minutes) compared to interictal period (188.8 minutes). There was a significant delay compared to nonmigrainous controls (migraine 188.8 minutes vs normal controls 111.8 minutes; P < .05). These data were replicated in percentage of radioactive material remaining in the stomach at 2 hours. Conclusions.—Contrary to previous belief, this study has demonstrated that migraineurs suffer from gastric stasis both during and outside an acute migraine attack. This may suggest that migraineurs may have an abnormal autonomic function compared to nonmigrainous controls. The potential role of this in pathophysiology of migraine is discussed and avenues for further investigations are explored.

Migraine changes with age: IMPACT on migraine classification.

Abstract: Objective.—To establish if criteria for the diagnosis of migraine change with age and to document the influence of age on the full spectrum of migraine features. Also to define the clinical spectrum and provide a prognostic profile of migraine stratified by age. Background.—Few studies have formally analyzed migraine characteristics stratified by age in a large cohort of patients. Methods.—One thousand nine consecutive patients meeting ICHD-2, 1.1, 1.2, and 1.5.1 at their initial office visit were studied. Patients were stratified by age into 3 groups: group I, 16 to 29, group II, 30 to 49, and group III, 50 years or older. Variables studied included gender, headache duration in years, prodrome, aura, postdrome, headache triggers, headache characteristics, associated symptoms, headache location, headache frequency, headache days, and disability. Ordinal variables were graded from 0 to 3 but only grades greater than grade 1 (more than occasional) were used in the study. Results.—A total of 86.3% patients were female and mean age was 37.7 years ± 11.7 years (range 16 to 80), headache duration 15.0 years, and headache frequency 10 headaches per month. Study Results: No significant age differences were seen in gender, or frequency of prodrome, aura, or postdrome. In patients with aura the percentage of headaches with aura significantly decreased with age. Headache triggers, in general, showed no age differences; specific triggers showed statistical differences: stress as a trigger decreased with age; alcohol, smoke, and neck pain triggers increased with age, while in women hormones as a trigger peaked markedly in the 30- to 49-year-old age group compared with the other ages. Exercise, food, not eating, heat, lights, perfume, sex, sleep disturbance, sleeping late, and weather triggers showed no significant differences in age. Headache location showed no differences except for neck location, which significantly increased with age. Associated symptoms of photophobia, phonophobia, dizziness decreased with age and running of the nose/tearing of the eyes increased with age. Nausea, vomiting, osmophobia, taste abnormalities, and diarrhea showed no significant differences. Headache quality showed decreasing throbbing, pressure, and stabbing with age, but aching showed no statistical difference. Being forced to sleep or rest with headache showed a significant decrease with age, but no significant differences were seen in other acute migraine characteristics, including choose to sleep or rest with headache, function during headache, average intensity and duration of headache, recurrence rate of headache, headache aggravation by activity, response to acute medication, and acute medication satisfaction. The 50+ age group tended to have less dizziness, photophobia, phonophobia, nausea, vomiting, temporal location, throbbing, pressure, stabbing, headache days, moderate days, severe days, aggravation of headache by activity, and recurrence but tended to have more mild days, greater ability to function during headache, and greatest response to acute medication. Despite no difference from other groups in headache intensity and duration of headache, these findings taken together seem to reflect a “lesser migraine” in the 50+ age group. Conclusions.—This study highlights specific age differences in migraineurs, in most instances showing an age decline in frequency of variables, such as stress as a trigger, photophobia, phonophobia, dizziness, throbbing, pressure, stabbing, and being forced to sleep or rest with headache. Hormones as a trigger peaked in women in the 30- to 49-year-old age group. Increases with age were seen with alcohol, smoke, and neck pain triggers, neck location, and running of the nose/tearing of the eyes. The 50+ age group showed trends suggesting a “lesser acute migraine attack.” These findings support the concept of lessening features of migraine over time resulting in a lower prevalence of migraine in older patients.

Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study.

Abstract: Objective.—Compare the effectiveness of a combination analgesic containing acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of migraine. Methods.—Multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study. A total of 1555 migraineurs were included in the analysis. No patients were excluded solely because of severity of symptoms or degree of disability. A single 2-tablet dose for each of the 3 treatment groups: a combination product containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or matching placebo. The primary efficacy endpoint was the weighted sum of pain relief (PAR) scores at 2 hours postdose (TOTPAR2) and an important secondary endpoint was the time to onset of meaningful relief. Results.—There were 669 patients in the AAC group, 666 patients in the IB group, and 220 patients in the placebo group. The 3 treatment groups had similar demographic profiles, migraine histories, and baseline symptom profiles. While both active treatments were significantly better than placebo in relieving the pain and associated symptoms of migraine, AAC was superior to IB for TOTPAR2, as well as for PAR, time to onset of meaningful PAR, pain intensity reduction, headache response, and pain free. The mean TOTPAR2 scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0, respectively (AAC vs. IB, P < .03). The median time to meaningful PAR for AAC was 20 minutes earlier than that of IB (P < .036). Conclusion.—AAC and IB are safe, cost-effective treatments for migraine; AAC provides significantly superior efficacy and speed of onset compared with IB.

Pharmacology of dihydroergotamine and evidence for efficacy and safety in migraine.

Abstract: Dihydroergotamine mesylate (DHE), an ergot alkaloid, has been extensively utilized and studied in the treatment of episodic and chronic migraine. This article reviews the pharmacokinetics, pharmacodynamics, and clinical efficacy and safety of DHE, particularly in comparison to ergotamine tartrate (ET), a similar ergot alkaloid with a long history of use in the treatment of migraine. Structural differences between these 2 compounds account for clinically important distinctions in their pharmacokinetic, pharmacodynamic, and adverse event profiles. DHE is a significantly less potent arterioconstrictor than is ET, which makes it a potentially much safer drug. In addition, DHE is associated with a markedly lower incidence of medication-withdrawal headache, nausea, and vomiting than is ET. The safety and efficacy data presented here are derived from clinical trials and case series involving DHE administered by intravenous infusion, intramuscular or subcutaneous injection, or intranasal spray.

"Benign" imaging abnormalities in children and adolescents with headache.

Abstract: Objective.—To study the frequency of “benign” abnormalities on brain imaging in children with headache, compare it with the frequency of imaging findings that dictate a change in patient management, and determine the association of benign findings with headache. Methods.—A database of 681 headache patients from the pediatric outpatient neurology department over 2 years was reviewed. Patients with benign imaging abnormalities were compared to those with nonbenign findings. Benign abnormalities were defined as those that did not result in a change in patient management. Using literature review, we discuss the benign findings and their possible association with headache. Results.—Two-hundred and forty-one patients (35.4%) had imaging at our facility. Two-hundred and eighteen had brain magnetic resonance imaging and 23 had brain computed tomography (CT) only. Twenty-two patients had CT of the sinuses in addition to brain imaging. Forty-six (19.1%) were found to have 50 benign abnormalities including 13 sinus disease, 11 Chiari I malformations, 7 nonspecific white matter abnormalities, 5 venous angiomas, 5 arachnoid cysts, 4 enlarged Virchow–Robin spaces, 2 pineal cysts, 1 mega cisterna magna, 1 fenestration of the proximal basilar artery, and 1 periventricular leukomalacia. Twenty-three patients (9.5%) had findings requiring a change in management. These included 5 sinus disease, 4 tumors, 4 old infarcts, 3 Chiari I, 2 moyamoya, 1 intracranial vascular stenosis, 1 internal jugular vein occlusion, 1 arteriovenous malformation, 1 demyelinating disease, and 1 intracerebral hemorrhage. When excluding sinusitis, which was evident clinically prior to imaging, 3 patients had absence of abnormal neurologic symptoms and signs and imaging findings that resulted in a change in management. Conclusions.—Approximately 20% of pediatric headache patients with brain imaging have benign abnormalities that do not result in a change in headache management. Imaging findings that require a change in management are rare in patients with an absence of abnormal neurologic symptoms and signs, occurring in 1.2% of patients imaged in this study.

Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period.

Abstract: Objectives—To evaluate the substances associated with medication overuse headache (MOH) in a headache center, over the course of the past 15 years Background—The acute treatment of migraine has substantially changed over the past 15 years, and therefore, the substances associated with MOH may have changed as well Methods—We randomly reviewed charts of subjects seen during the years of 2005, 2000, 1995, and 1990, to identify substances associated with MOH Since the criteria proposed by the second edition of the International Classification of Headache Disorders require causal attribution, demonstrated by improvement after withdrawal (and this was not assessed in this study), herein we refer to probable MOH (PMOH) We contrasted the substances associated with PMOH over the studied years Results—Our sample consists of 1200 individuals, 300 per year of interest The proportions of subjects with a diagnosis of PMOH remained stable over the years, varying from 64% of all cases seen in the center in 1990, to 593% in 2005 We found a significant decrease in the relative frequency of probable ergotamine overuse headache (from 186% to 0%, P < 0001), and in probable combination analgesic overuse headache (from 422% to 136%, P < 0001) The differences were not significant for opioid overuse headache The relative frequency increased significantly for the triptans (from 0% to 216%, P < 0001), simple analgesics (from 88% to 318%, P < 05), and for combinations of acute medications (from 98% to 227%, P= 01) Conclusion—While overuse of acute medications remains an important problem in the tertiary care arena, the substances associated with the overuse have dramatically changed over the past 15 years Educational initiatives should emphasize that the newer specific acute migraine medications (triptans) may also be associated with PMOH

Medication Overuse Headache: Biobehavioral Issues and Solutions

Abstract: This article reviews current research on medication-overuse headache (MOH), and provides clinical suggestions for effective treatment programs. Epidemiological research has identified reliance on analgesics as a predictive factor in headache chronicity. MOH can be distinguished as simple (Type I) or complex (Type II). Simple cases involve relatively short-term drug overuse, relatively modest amounts of overused medications, minimal psychiatric contribution, and no history of relapse after drug withdrawal. In contrast, complex cases often present with multiple psychiatric comorbidities and a history of relapse. Although limited, current research suggests that comorbid psychiatric disorders are more prevalent in MOH than in control headache conditions, and may precede the onset of MOH. There appears to be an elevated risk of family history of substance use disorders in MOH patients, and an increased risk of MOH in patients with diagnosed personality disorders. Current studies suggest a high rate of relapse at 3 to 4 years after drug withdrawal and pharmacological treatment, with most relapse occurring during the first year of treatment. Relapse is a greater problem with analgesics than ergots or triptans. The addition of behavioral treatment to prophylactic medication may significantly reduce the risk of relapse over a period of several years. Clinical recommendations include assessment and modification of psychological factors that may underlie MOH, provision of detailed educational information, and combining behavioral treatment with the current standard of drug withdrawal and use of prophylactic pharmacotherapy.

Visual stimuli are common triggers of migraine and are associated with pattern glare.

Abstract: Objective.—To investigate the associations between interictal pattern glare, visual stress, and visual triggers of migraine. Background.—There has been relatively little research on the visual stimuli that can trigger migraine episodes. This is surprising, since if practitioners can obviate such triggers, then some attacks may be prevented. The existing literature suggests that patients who are prone to visually triggered migraines report more illusions on viewing striped patterns (“pattern glare”) and that colored filters may be an effective intervention for these people. Methods.—Headache symptoms and headache triggers were investigated in migraine and control groups in 2 separate experiments. In one experiment, we also determined, for each participant, pattern glare, whether it was reduced by colored filters and, if so, what the optimum color of filter was. Color vision was also assessed with the D15 test. Results.—People with migraine saw significantly more illusions on viewing each striped pattern and experienced greater pattern glare. They were also more likely to select a colored filter to aid visual comfort, particularly colors in the blue-to-green sector of the spectrum. Color vision was impaired subtly but significantly in migraine. Principal component analyses grouped common headache triggers into 5 broadly equal components: food, visual triggers, alcohol, stress and tiredness, and the environment. In a second analysis, the overall number of illusions seen in striped patterns was associated with visual triggers while pattern glare, use of colored filters, and interictal light sensitivity together formed a sixth component interpreted as visual stress. Conclusions.—It is suggested that clinicians should ask migraine patients whether visual stimuli trigger their migraine, about interictal visual symptoms, and use the pattern glare test to ensure that those who may benefit from optometric interventions are appropriately managed.

Recognition and Therapeutic Management of Migraine in 2004, in France: Results of FRAMIG 3, a French Nationwide Population‐Based Survey

Abstract: Objective.—To evaluate the proportion of migraineurs who are self-aware of their disease in France, to determine the factors (disability, quality of life, psychiatric comorbidities, and medical consultation) that may promote self-awareness of migraine, and to assess the influence of these factors on migraine attacks. Background.—New recommendations for migraine diagnosis and medical management were released in 2003 by the French medicoeconomic evaluation service (ANAES). In addition, the revised classification of headache disorders recently issued by the International Headache Society includes probable migraine as a form of migraine. However, strict and probable migraine now appear to be part of the same spectrum of disease. Methods.—Subjects with migraine (strict or probable) according to the revised classification were identified by a postal questionnaire from a large representative sample of the French adult population. Migraine-related disability was assessed using the MIDAS questionnaire, anxiety and depression by the Hospital Anxiety and Depression scale (HADS), and health-related quality of life (HRQoL) by the 8 concepts of the Short-Form 12 (SF-12) questionnaire. Migraine management was assessed according to the use of recommended or nonrecommended treatments, and treatment efficacy according to the set of 4 questions designed by the ANAES. Results.—Of the 10,532 subjects interviewed, 1,179 subjects (21.3%) were identified as migraineurs. Sixty percent of all migraine subjects were not self-aware that they had migraine. Medical consultation, duration of migraine history, severe intensity of attacks, impact on daily living, and female gender promoted self-awareness of migraine. On the other hand, HRQoL and anxiety and depression scores were not different between subjects self-aware or not self-aware of migraine. Only 20% of all migraine subjects were medically followed-up. Quality of the first medical consultation appears determinant for continued consulting. Subjects self-aware of migraine more frequently used recommended acute treatments of migraine, which proved more effective than nonrecommended treatments as assessed according to the ANAES set of questions. Conclusions.—Migraine medical diagnosis and follow-up remain low in France. Careful medical consultation is a prime factor for migraine subject self-awareness of migraine, continued consultation, and use of recommended medications for the treatment of migraine attacks.

Pain characteristics of the acute migraine attack.

Abstract: Objectives.—This study describes the pain characteristics of the acute migraine attack, including time of onset, time to peak, duration, intensity, quality, aggravation by activity, as well as recurrence frequency and time to recurrence, in a tertiary care practice. Background.—The literature documenting the characteristics of the pain of the acute attack of migraine is sparse. Methods.—A total of 1283 migraine patients (ICHD 1.1, 1.2, 1.5.1, and ICHD 1.6 [total migraine population]) were evaluated at first visit. Headache character (throbbing, aching, pressure, stabbing scaled grade 0 to 3; 0 = none; 1 = mild; 2 = moderate; 3 = severe), intensity (for average, minimum, and maximum intensity headaches, scaled 0 to 10), lifetime duration, frequency per month, duration in minutes (for average, minimum, maximum duration headaches), time of onset of headache (morning, afternoon, evening, night, anytime), aggravation of headache with activity (scaled 0 to 3), percentage recurrence, time to recurrence, were recorded. Patients were stratified into different groups; ICHD 1.1, 1.2, and 1.5.1 (migraine) ICHD 1.1 and 1.2 (episodic migraine), ICHD 1.5.1 (chronic migraine), and ICHD 1.6 (probable migraine). Patients with unremitting daily headache were excluded. Results.—Demographics: A total of 84.3% patients were female, and the mean age was 37.7, ranging from 13.0 to 80.5 years. Eight hundred seventy-four patients were classified as ICHD 1.1, 1.2, and 1.5.1 (migraine), 524 with ICHD 1.1 and 1.2 (episodic migraine), 350 with ICHD 1.5.1 (chronic migraine), and 409 with ICHD 1.6 (probable migraine). Study Results: Time of onset of headache was mostly in the morning in 18.7%, afternoon 13.5%, evening 4.0%, during night 9.4%, and “anytime” 54.3%, with minor differences seen in different headache types, gender, presence of aura, and headache frequency. The median time to peak of the headache was greater in migraine than probable migraine (90 minutes vs. 60 minutes; P < .01). Headache duration medians were reported as minimum of 12 hours, maximum of 48 hours with an average of 24 hours, females being greater than males in average headache (24.0 vs. 12.0; P < .01), minimum (24.0 vs. 8; P < .05), and maximum (48.0 vs. 24.0; P < .01). Only the minimum duration differed between migraine and atypical migraine (12.0 vs. 4.0; P < .01). Headache intensity medians were as follows: average intensity 7/10, minimum 4/10, and maximum 10/10, with no differences in migraine versus probable migraine, gender, or headache frequency. Headache intensity median was consistently greater in migraine episodic than chronic migraine (average 8.0 vs. 6.5, minimum 4.5 vs. 3.0, maximum 10.0 vs. 9.0, all P < .05). Headache character (greater than grade 1) was throbbing (73.5%), aching (73.8%), pressure (75.4%), and stabbing (42.6%) with significantly more throbbing in migraine than in probable migraine (73.5% vs. 63.2%; P < .01) and more aching in chronic than in episodic migraine (65.4% vs. 63.1%; P < .05). Headache increased by activity was present in 90.2% of patients, grade 1 in 13.8%, grade 2 in 30.8%, and grade 3 in 45.5% of patients. The presence of activity aggravating headache was more likely to be associated with headache triggers, maximum headache severity, longer time to 50% reduction of headache, and longer time to absent headache with triptans, and more headache-associated symptoms, and longer postdrome duration (all P < .05). Recurrence rate was 43.8% with the median time to recurrence being 8 hours. Significantly less recurrence occurred with episodic than chronic migraine (30.0% vs. 50.0%; P < .01). Conclusions.—This study provides an in-depth description of pain features in the acute migraine attack. It was found that a significant number of patients need to be provided with the means of treating headache rapidly in at least some of their headaches and that headache recurrence needs to be addressed in a large number of patients.

Noise as a trigger for headaches: relationship between exposure and sensitivity.

Abstract: OBJECTIVE - This study investigated how triggers acquire the capacity to precipitate headaches. BACKGROUND - Traditional clinical advice is that the best way to prevent headache/migraine is to avoid the triggers. Avoidance of anxiety-eliciting stimuli, however, results in sensitization to the stimuli, so is there a danger that avoidance of migraine/headache triggers results in decreased tolerance for the triggers. DESIGN - One hundred and fifty subjects, 60 of whom suffered from regular headaches, were randomly assigned to 5 experimental conditions, defined by length of exposure to the headache trigger of noise. METHODS - Subjects attended a laboratory session divided into 3 phases: preintervention test, intervention (1 of 5 levels of exposure to the trigger), and postintervention test. Response to the intervention was measured in terms of noise tolerance, sensitivity to noise, and nociceptive response to noise. RESULTS - A curvilinear relationship was found between length of exposure to the trigger and pain response for individuals who do not suffer from regular headaches, that is, short exposure was associated with sensitization and prolonged exposure with desensitization. The relationship for headache patients was less clear. CONCLUSIONS - The findings are consistent with the proposition that 1 etiological pathway to suffering from frequent headaches is via trying to avoid, or escape from, potential trigger factors. These results suggest that the traditional clinical advice to headache patients, that the best way to prevent migraine/headache is to avoid the triggers, runs the risk of establishing an insidious sensitization process thereby increasing headache frequency.