Showing papers in "Headache in 2012"

Chronic Migraine Prevalence, Disability, and Sociodemographic Factors: Results From the American Migraine Prevalence and Prevention Study

Abstract: Objectives To estimate the prevalence and distribution of chronic migraine (CM) in the US population and compare the age- and sex-specific profiles of headache-related disability in persons with CM and episodic migraine. Background Global estimates of CM prevalence using various definitions typically range from 1.4% to 2.2%, but the influence of sociodemographic factors has not been completely characterized. Methods The American Migraine Prevalence and Prevention Study mailed surveys to a sample of 120,000 US households selected to represent the US population. Data on headache frequency, symptoms, sociodemographics, and headache-related disability (using the Migraine Disability Assessment Scale) were obtained. Modified Silberstein-Lipton criteria were used to classify CM (meeting International Classification of Headache Disorders, second edition, criteria for migraine with a headache frequency of ≥15 days over the preceding 3 months). Results Surveys were returned by 162,756 individuals aged ≥12 years; 19,189 individuals (11.79%) met International Classification of Headache Disorders, second edition, criteria for migraine (17.27% of females; 5.72% of males), and 0.91% met criteria for CM (1.29% of females; 0.48% of males). Relative to 12 to 17 year olds, the age- and sex-specific prevalence for CM peaked in the 40s at 1.89% (prevalence ratio 4.57; 95% confidence interval 3.13-6.67) for females and 0.79% (prevalence ratio 3.35; 95% confidence interval 1.99-5.63) for males. In univariate and adjusted models, CM prevalence was inversely related to annual household income. Lower income groups had higher rates of CM. Individuals with CM had greater headache-related disability than those with episodic migraine and were more likely to be in the highest Migraine Disability Assessment Scale grade (37.96% vs. 9.50%, respectively). Headache-related disability was highest among females with CM compared with males. CM represented 7.68% of migraine cases overall, and the proportion generally increased with age. Conclusions In the US population, the prevalence of CM was nearly 1%. In adjusted models, CM prevalence was highest among females, in mid-life, and in households with the lowest annual income. Severe headache-related disability was more common among persons with CM and most common among females with CM.

Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden.

Abstract: Objective To present results from the United States (US) Cluster Headache Survey including data on cluster headache demographics, clinical characteristics, suicidality, diagnostic delay, triggers, and personal burden. Background There are few large-scale studies looking at cluster headache patients and none from the USA. This manuscript will present data from The US Cluster Headache Survey, the largest survey ever completed of cluster headache patients living in the USA. Methods The total survey was composed of 187 multiple-choice questions that dealt with issues related to cluster headache including demographics, clinical characteristics, comorbid medical conditions, family history, triggers, smoking history, and personal burden. The survey was placed on a Web site from October through December 2008. Results A total of 1134 individuals completed the survey (816 male, 318 female). Some key highlights from the survey include the following: (1) diagnostic delay: there remains a significant diagnostic delay for cluster headache patients on average 5+ years with only 21% receiving a correct diagnosis at time of initial presentation. (2) Suicidality: suicidal ideations are substantial, occurring in 55%. (3) Eye color: the predominant eye color in cluster headache patients is brown and blue, not hazel as suggested in previous descriptions. (4) Laterality: cluster headache has a right-sided predominance. (5) Attack profile: in US cluster headache sufferers, most attacks occur between early evening and early morning hours with peak time of headache onset between midnight and 3 am; the circadian periodicity for cluster headache is present but is not as predominant in the population as previously thought. (6) Triggers: beer is the most common type of alcohol trigger in US cluster headache patients; noted migraine triggers such as weather changes and smells are also very common cluster headache triggers. (7) Medical comorbidities: peptic ulcer disease does not have a high prevalence in US cluster headache patients as suggested by previous literature; cluster headache is associated with a low prevalence of cardiac disease as well as cerebrovascular disease even though the majority of patients are chronic heavy smokers. In US cluster headache sufferers, there appears to be comorbidity with restless leg syndrome, and this has not been demonstrated in non-US cluster headache populations. (8) Personal burden: cluster headache is disabling to the individual as almost 20% of cluster headache patients have lost a job secondary to cluster headache, while another 8% are out of work or on disability secondary to their headaches. Conclusion Some findings from the US Cluster Headache Survey expound on what is currently known about cluster headache, while some of the results contradict what has been previously written, while other information is completely new about this fascinating headache disorder.

tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine.

Abstract: Objective.—We investigated in a sham-controlled trial the analgesic effects of a 4-week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high-resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation. Methods.—Thirteen patients with chronic migraine were randomized to receive 10 sessions of active or sham tDCS for 20 minutes with 2 mA over 4 weeks. Data were collected during baseline, treatment and follow-up. For the tDCS computational analysis, we adapted a high-resolution individualized model incorporating accurate segmentation of cortical and subcortical structures of interest. Results.—There was a significant interaction term (time vs group) for the main outcome (pain intensity) and for the length of migraine episodes (ANOVA,P < .05 for both analyses). Post-hoc analysis showed a significant improvement in the follow-up period for the active tDCS group only. Our computational modeling studies predicted electric current flow in multiple cortical and subcortical regions associated with migraine pathophysiology. Significant electric fields were generated, not only in targeted cortical regions but also in the insula, cingulate cortex, thalamus, and brainstem regions. Conclusions.—Our findings give preliminary evidence that patients with chronic migraine have a positive, but delayed, response to anodal tDCS of the primary motor cortex. These effects may be related to electrical currents induced in pain-related cortical and subcortical regions.

The Prevalence and Burden of Primary Headaches in China: A Population‐Based Door‐to‐Door Survey

Abstract: Objectives.— In the absence of reliable data on the prevalence and burden of primary headache disorders in the mainland of China, a population-based survey was initiated by Lifting The Burden: the Global Campaign against Headache. Methods.— Throughout all regions of China, 5041 non-related adult respondents aged 18-65 years were randomly sampled from the general population according to the expanded programme on immunization method established by World Health Organization. They were visited by door-to-door calling and surveyed using the structured questionnaire developed by Lifting The Burden, translated into Chinese and adapted to Chinese culture after a pilot study. Results.— The responder rate was 94.1%. The estimated 1-year prevalence of primary headache disorders was 23.8% (95% confidence interval 22.6-25.0%), of migraine 9.3% (95% confidence interval 8.5-10.1%), of tension-type headache (TTH) 10.8% (9.9-11.6%), and of chronic daily headache (CDH) 1.0% (0.7-1.2%). Of respondents with migraine, TTH, and CDH, moderate or severe impact and therefore high need for effective medical care were reported by 38.0%, 23.1%, and 47.9%, respectively. The World Health Organization quality of life-8 questionnaire showed that all 3 types of headache reduced life quality. The total estimated annual cost of primary headache disorders, including migraine, TTH, and CDH was CNY 672.7 billion, accounting for 2.24% of gross domestic product (GDP) (direct cost: CNY 108.8 billion, 0.36% of GDP; indirect cost: CNY 563.9 billion, 1.88% of GDP). Conclusion.— The prevalence of primary headaches is high in China and not dissimilar from the world average. These headaches cause disability, impair work, study and daily activities, decrease life quality, and bring about a heavy and hitherto unrecognized socioeconomic burden.

The 2012 AHS/AAN guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines.

Abstract: Background.— Updated guidelines for the preventive treatment of episodic migraine have been issued by the American Headache Society (AHS) and the American Academy of Neurology (AAN). We summarize key 2012 guideline recommendations and changes from previous guidelines. We review the characteristics, methods, consistency, and quality of the AHS/AAN guidelines in comparison with recently issued guidelines from other specialty societies. Methods.— To accomplish this, we reviewed the AHS/AAN guidelines and identified comparable recent guidelines through a systematic MEDLINE search. We extracted key data, and summarized and compared the key recommendations and assessed quality using the Appraisal of Guidelines Research and Evaluation-II (AGREE-II) tool. We identified 2 additional recent guidelines for migraine prevention from the Canadian Headache Society and the European Federation of Neurological Societies. All of the guidelines used structured methods to locate evidence and linked recommendations with assessment of the evidence, but they varied in the methods used to derive recommendations from that evidence. Results.— Overall, the 3 guidelines were consistent in their recommendations of treatments for first-line use. All rated topiramate, divalproex/sodium valproate, propranolol, and metoprolol as having the highest level of evidence. In contrast, recommendations diverged substantially for gabapentin and feverfew. The overall quality of the guidelines ranged from 2 to 6 out of 7 on the AGREE-II tool. Conclusion.— The AHS/AAN and Canadian guidelines are recommended for use on the basis of the AGREE-II quality assessment. Recommendations for the future development of clinical practice guidelines in migraine are provided. In particular, efforts should be made to ensure that guidelines are regularly updated and that guideline developers strive to locate and incorporate unpublished clinical trial evidence.

Headache impact of chronic and episodic migraine: results from the American Migraine Prevalence and Prevention study.

Abstract: Background.— The Headache Impact Test-6 (HIT-6) has been demonstrated to be a reliable and valid measure that assesses the impact of headaches on the lives of persons with migraine. Originally used in studies of episodic migraine (EM), HIT-6 is finding increasing applications in chronic migraine (CM) research. Objectives.— (1) To examine the headache-impact on persons with migraine (EM and CM) using HIT-6 in a large population sample; (2) to identify predictors of headache-impact in this sample; (3) to assess the magnitude of effect for significant predictors of headache-impact in this sample. Methods.— The American Migraine Prevalence and Prevention study is a longitudinal, population-based study that collected data from persons with severe headache from 2004 to 2009 through annual, mailed surveys. Respondents to the 2009 survey who met International Classification of Headache Disorders 2 criteria for migraine reported at least 1 headache in the preceding year, and completed the HIT-6 questionnaire were included in the present analysis. Persons with migraine were categorized as EM (average <15 headache days per month) or CM (average ≥15 headache days per month). Predictors of headache-impact examined include: sociodemographics; headache days per month; a composite migraine symptom severity score (MSS); an average pain severity rating during the most recent long-duration headache; depression; and anxiety. HIT-6 scores were analyzed both as continuous sum scores and using the standard, validated categories: no impact; some impact; substantial impact; and severe impact. Group contrasts were based on descriptive statistics along with linear regression models. Multiple imputation techniques were used to manage missing data. Results.— There were 7169 eligible respondents (CM = 373, EM = 6554). HIT-6 scores were normally distributed. After converting sum HIT-6 scores to the standard categories, those with CM were significantly more likely to experience “severe” headache impact (72.9% vs 42.3%) and had higher odds of greater adverse headache impact compared with persons with EM (OR = 3.5, 95% CI = 2.77-4.41, P < .0001). Significant predictors of adverse headache impact in both groups included younger age, higher MSS score, higher average long-duration headache pain severity rating, and depression. Lower annual household income, anxiety, and higher standardized headache day frequency predicted adverse headache impact in EM but not CM. With few exceptions, gender, race, and body mass index did not significantly predict adverse headache impact. Finally, rates of depression were more than double among persons with CM (CM = 25.2%, EM = 10.0%), and rates of anxiety were nearly triple (CM = 23.6%, EM = 8.5%). Conclusions.— This work further establishes HIT-6 as a useful instrument for characterizing CM and understanding the increased disease related burden. Persons with CM had significantly higher odds of greater adverse headache impact, when compared with EM. Predictors of greater headache impact for both groups included higher MSS scores, higher average headache pain severity, and depression. Additional predictors unique to EM included higher average household income, younger age, higher standardized headache day frequency, and anxiety. This finding may be related to differences in sample size and power. Further exploration is warranted.

CGRP and NO in the trigeminal system: mechanisms and role in headache generation.

Abstract: Calcitonin gene-related peptide (CGRP) and metabolic products of nitric oxide (NO) are increased in jugular venous plasma during migraine attacks and other primary headaches. Patients suffering from primary headaches are particularly sensitive to CGRP and NO donors responding with delayed headaches to an infusion of either of these substances. Accordingly, both CGRP and NO are considered as key mediators in migraine, and clinical trials have shown that inhibitors of CGRP receptors and NO synthase are effective in treating migraine. There is an implicit understanding that CGRP and NO systems interact, and here, we review the body of preclinical work on these systems focusing on the trigeminovascular system in migraine. NO derives from various cell types via 3 isoforms of NO synthase, whereas CGRP is produced from a subset of trigeminal afferents. In rodents, NO donors cause activity alterations on different levels of the trigeminal system including enhancement of CGRP release, which in turn results in arterial vasodilatation and possibly mast cell degranulation in the meninges. The activity of spinal trigeminal neurons, which is a sensitive integrative measure for trigeminal activity, is partly under the control of CGRP and NO. Both mediators facilitate nociceptive transmission, possibly via presynaptic mechanisms. These functions are supported by immunolocalization of CGRP receptor components on 3 trigeminovascular levels: cranial dura mater, trigeminal ganglion, and spinal trigeminal nucleus. Current data support a relationship of CGRP and NO actions on all levels of the trigeminovascular system and emphasize central CGRP receptors as possible therapeutic targets.

Beyond neurovascular: migraine as a dysfunctional neurolimbic pain network.

Abstract: No single model of migraine explains all of the known features of the disorder. Migraine has recently been characterized as an abnormality in pain-modulating circuits in the brainstem. The periaqueductal gray appears to have a critical role in migraine genesis and has been labeled the "migraine generator." The concept of a "pain matrix," rather than a specific locus of pain, is widely accepted in the pain literature and offers a new dimension to understanding migraine. Recent neuroimaging studies of migraineurs suggest altered functional connectivity between brainstem pain-modulating circuits and cortical (limbic) centers. Numerous clinical observations suggest that limbic influences play an important role in migraine expression. We propose a model of migraine as a dysfunction of a "neurolimbic" pain network. The influence between brainstem and cortical centers is bidirectional, reflecting the bidirectional interaction of pain and mood. Neurolimbic dysfunction may increase as migraine becomes more chronic or refractory. The neurolimbic model expands the model of migraine as a dysfunction of brainstem nuclei. A neurolimbic model may help bridge a gap in understanding the migraine attack, the interictal dysfunctions of episodic migraine, the progression to chronic migraine, and the common comorbidities with other disorders (such as fibromyalgia, irritable bowel syndrome, and mood and anxiety disorders), which may also be considered neurolimbic. A neurolimbic model of migraine may be a useful heuristic that would impact both clinical treatment and research agendas, as well as education of physicians and patients.

Validating Migraine-Specific Quality of Life Questionnaire v2.1 in Episodic and Chronic Migraine

Abstract: Objective.— To provide evidence for the reliability and validity of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ) for use in chronic migraine (CM) in adults. Background.— MSQ is one of the most frequently utilized disease-specific tools assessing impact of migraine on health-related quality of life (HRQL). However, evidence for its reliability and validity are based on studies in episodic migraine (EM) populations. Additional studies assessing the reliability and validity of the MSQ in patients with CM are needed. Methods.— Cross-sectional data were collected via web-based survey in 9 countries/regions. Participants were classified as having CM (≥15 headache days/month) or EM (<15 headache days/month). Three MSQ domains – Role Function-Preventive (RP), Role Function-Restrictive (RR), and Emotional Function (EF) – were rescaled to 0-100, where higher scores indicate better HRQL, and analyzed for internal consistency reliability (Cronbach's α), construct validity (correlations between MSQ scales and measures of depression/anxiety [Patient Health Questionnaire; PHQ-4], disability [Migraine Disability Assessment Questionnaire; MIDAS], and functional impact [Headache Impact Test; HIT-6], where lower scores indicate better HRQL for each measure), as well as discriminant validity across migraine groups. Results.— A total of 8726 eligible respondents were classified: 5.7% CM (n = 499) and 94.3% EM (n = 8227). Subjects were mostly female (83.5%) with a mean (±SD) age of 40.3 ± 11.4, and were similar between the 2 groups. MSQ domain scores for CM and EM groups, respectively, were: RP = 61.4 ± 26.1 and 71.7 ± 24.0; RR = 44.4 ± 22.1 and 56.5 ± 24.1; EF = 48.3 ± 28.1 and 67.2 ± 26.7. Internal consistency of the overall sample for RP, RR, and EF was 0.90, 0.96, and 0.87, respectively. Similar values were observed for CM and EM. MSQ scores for the overall sample correlated moderately to highly with scores from the PHQ-4 (r = −0.21 to −0.42), MIDAS (r = −0.38 to −0.39), and HIT-6 (r = −0.60 to −0.71). Similar values were observed for CM and EM. Known-groups validity indicated significant differences (P < .0001) in the hypothesized direction between CM and EM for RP (F = 86.19), RR (F = 119.24), and EF (F = 235.90). Conclusion.— The MSQ is a reliable and valid questionnaire in the CM population that can differentiate the functional impact between CM and EM. The MSQ can assist researchers in evaluating treatment effectiveness by obtaining input directly from the patients on multidimensional aspects other than frequency of headache days. (Headache 2012;52:409-421)

Opioid use and dependence among persons with migraine: results of the AMPP study.

Abstract: Objective.— To assess the frequency of opioid use for acute migraine treatment and characterize use groups by sociodemographics, health-care resource utilization (HRU), comorbidities and probable dependence within a large, US population-based sample of persons with migraine. Background.— Opioids are used in the acute treatment of migraine. However, their use is controversial. Methods.— Data from the 2009 American Migraine Prevalence and Prevention (AMPP) study were used to categorize persons with migraine into 4 groups based on reported opioid use: nonusers (between 2005 and 2009), previous users (history of use between 2005 and 2008 but no-use in 2009), and current opioid users (those reporting use of opioids in the 3 months preceding the 2009 American Migraine Prevalence and Prevention survey). Current opioid users were divided into nondependent and probable dependence users according to criteria for dependence adapted for inclusion in the survey from the Diagnostic and Statistical Manual of Mental Disorders–4th edition. All opioid-use groups were contrasted by sociodemographics, headache characteristics, medical and psychiatric comorbidities (depression [measured by the Patient Health Questionnaire-9], anxiety [measured by the Primary Care Evaluation of Mental Health Disorders, PRIME-MD], and cardiovascular events and risk factors), and headache-related HRU. Results.— In a sample of 5796 migraineurs, 4076 (70.3%) were opioid nonusers, 798 (13.8%) were previous users, and 922 (15.9%) were current opioid users. Among current opioid users, 153 (16.6%) met criteria for probable dependence and 769 (83.4%) did not. Headache-related disability (Migraine Disability Assessment sum scores) increased across groups as follows: nonusers: 7.8, previous users: 13.3, current nondependent users: 19.1, and current probable dependence users: 44.4, as did monthly headache frequency: nonusers: 3.2 days/month, previous users: 4.3 days/month, current nondependent users: 5.6 days/month, and current probable dependence users: 8.6 days/month. The prevalence of depression and anxiety was highest among current users with probable dependence. Rates of headache-related HRU were higher for all opioid-use groups for emergency department/urgent care, primary care, and specialty care visits compared to nonusers. Conclusions.— Opioid use for migraine is associated with more severe headache-related disability, symptomology, comorbidities (depression, anxiety, and cardiovascular disease and events), and greater HRU for headache. Longitudinal studies are needed to further assess the directionality and causality between opioid use and the outcomes we examined.

A Randomized Trial of a Web-based Intervention to Improve Migraine Self-Management and Coping

Abstract: Objective Test the clinical efficacy of a web-based intervention designed to increase patient self-efficacy to perform headache self-management activities and symptom management strategies; and reduce migraine-related psychological distress.

Rescue Therapy for Acute Migraine, Part 3: Opioids, NSAIDs, Steroids, and Post-Discharge Medications

Abstract: Objective.— The final section of this 3-part review analyzes published reports involving the acute treatment of migraine with opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids in the emergency department (ED), urgent care, and headache clinic settings, as well as post-discharge medications. In the Conclusion, there is a general discussion of all the therapies presented in the 3 sections. Method.— Using the terms (“migraine” AND “emergency”) AND (“therapy” OR “treatment”), the author searched MEDLINE for reports from ED and urgent care settings that involved all routes of medication delivery. Reports from headache clinic settings were included only if medications were delivered by a parenteral route. Results.— Seventy-five reports were identified that compared the efficacy and safety of multiple acute migraine medications for rescue. Of the medications reviewed in Part 3, opioids, NSAIDs, and steroids all demonstrated some effectiveness. When used alone, nalbuphine and metamizole were superior to placebo. NSAIDs were inferior to the combination of metoclopramide and diphenhydramine. Meperidine was arguably equivalent when compared with ketorolac and dihydroergotamine (DHE) but was inferior to chlorpromazine and equivalent to the other dopamine antagonists. Steroids afford some protection against headache recurrence after the patient leaves the treatment center. Conclusions.— All 3 opioids most frequently studied – meperidine, tramadol, and nalbuphine – were superior to placebo in relieving migraine pain, although meperidine combined with promethazine was not. Opioid side effects included dizziness, sedation, and nausea. With ketorolac being the most frequently studied drug in the class, NSAIDs were generally well tolerated, and they may provide benefit even when given late in the migraine attack. The rate of headache recurrence within 24-72 hours after discharge from the ED can be greater than 50%. Corticosteroids can be useful in reducing headache recurrence after discharge. As discussed in Parts 1, 2, and 3, there are effective medications for provider-administered “rescue” in all the classes discussed. Prochlorperazine and metoclopramide are the most frequently studied of the anti-migraine medications in the emergent setting, and their effectiveness is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in migraine pain relief. Although there are fewer studies involving sumatriptan and DHE, relatively “migraine-specific” medications, they appear to be equivalent to the dopamine antagonists for migraine pain relief. Lack of comparisons with placebo and the frequent use of combinations of medications in treatment arms complicate the comparison of single agents to one another. When used alone, prochlorperazine, promethazine, metoclopramide, nalbuphine, and metamizole were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also are more likely to produce side effects that are difficult for a patient to tolerate (especially akathisia). Metoclopramide was equivalent to prochlorperazine, and, when combined with diphenhydramine, was superior in efficacy to triptans and NSAIDs. Meperidine was arguably equivalent when compared with ketorolac and DHE but was inferior to chlorpromazine and equivalent to the other neuroleptics. Sumatriptan was inferior or equivalent to the neuroleptics and equivalent to DHE when only paired comparisons were considered. The overall percentage of patients with pain relief after taking sumatriptan was equivalent to that observed with droperidol or prochlorperazine. (Headache 2012;52:467-482)

Anxiety, Depression, and Pain in Burning Mouth Syndrome: First Chicken or Egg?

Abstract: Background.—Burning mouth syndrome (BMS) is an idiopathic and chronic pain condition for which patients may experience high levels of pain, anxiety, and depression. So far, it has not yet been well investigated whether specific psychiatric features (anxious traits, personality disorder, or somatization) may play a role in the BMS pathogenesis or whether some BMS symptoms, or BMS itself, may cause secondary psychiatric symptoms. Objective.—The aim of this study was to evaluate the relationship between pain, depression, and anxiety in BMS and healthy patients in order to hypothesize a possible underlying pathogenetic model. Methods.—Fifty-three patients with BMS and 51 healthy volunteers matched for sex and age were enrolled. All patients underwent a physical examination, laboratory screening tests, and psychiatric assessment with the following instruments: Visual Analog Scale, the Hamilton Rating Scale for Depression, the State-Trait Anxiety Inventory Form Y 1-2 (STAI Y1-Y2), and the Symptom Checklist-90-Revised (SCL-90-R). Results.—BMS patients and healthy volunteers showed a statistically significant difference in psychiatric features: Regression analysis showed that pain is affected by depression (R = 0.373; R 2 corrected = 0.123; F = 8.563; P < .005), and depression is affected by anxiety (R = 0.512; R 2 corrected = 0.248; F = 18.519; P < .001). BMS patients have statistically significant higher scores of anxiety (STAI Y1, P = .026 and STAI Y2, P = .046) and depression (P < .001), and higher SCL-90-R scores on somatization (P = .036) and hostility dimensions (P = .028) than the control group. Conclusions.—We may hypothesize that anxiety could determine a secondary demoralization in BMS patients (depression) and depressive symptoms could contribute to pain, accordingly. Therefore, pain could be a somatic feature of depression. Our findings provide an example of a possible pathogenetic model for BMS.

The Effectiveness of a Group-Based Acceptance and Commitment Additive Therapy on Rehabilitation of Female Outpatients With Chronic Headache: Preliminary Findings Reducing 3 Dimensions of Headache Impact

Abstract: Objective.— Examine whether acceptance and commitment additive therapy is effective in reducing the experience of sensory pain, disability, and affective distress because of chronic headache in a sample of outpatient Iranian females. Background.— Chronic headaches have a striking impact on sufferers in terms of pain, disability, and affective distress. Although several Acceptance and Commitment Therapy outcome studies for chronic pain have been conducted, their findings cannot be completely generalized to chronic headaches because headache-related treatment outcome studies have a different emphasis in both provision and outcomes. Moreover, the possible role of Iranian social and cultural contexts and of gender-consistent issues involved in Acceptance and Commitment Therapy outcomes deserve consideration. Methods.— This study used a randomized pretest–post-test control group design. The sample was selected from consecutive female outpatients with chronic headache, attending and/or referred to a headache clinic in a governmental hospital from April 2011 to June 2011. In total, 80 female outpatients were interviewed, and after implementing inclusion/exclusion criteria, thirty females were considered eligible to participate in the study. Half (n = 15) were randomly selected to participate in the treatment group. Four participants of this group failed to complete the treatment sessions (n = 11). The Acceptance and Commitment Therapy group received the medical treatment as usual and 8 sessions of Acceptance and Commitment Therapy. The other half (n = 15) served as the control group that received only medical treatment as usual. The short form of McGill pain questionnaire, the migraine disability assessment scale, and the trait subscale of the state-trait anxiety inventory were administered, which operationalized 3 dimensions of impact of chronic headache, sensory pain, disability, and emotional distress, respectively, to explore the impact of recurrent headache episodes. Pretest and post-test measures on these 3 dimensions of impact were the primary outcome measures of this study. Analyses of covariance with the pretreatment score used as a covariate were conducted on pain intensity, degree of disability, and level of affective distress before and after therapy to assess therapeutic intervention effectiveness. Results.— Chronic tension type of headache (63%) and chronic migraine without aura (37%) were the headache types reported by the participants. Data analyses indicated the significant reduction in disability (F[1,29] = 33.72, P < .0001) and affective distress (F[1,29] = 28.27, P < .0001), but not in reported sensory aspect of pain (F[1,29] = .81, P = .574), in the treatment group in comparison with the control group. Conclusions.— The effectiveness of a brief acceptance and commitment additive therapy in the treatment of Iranian outpatient females with chronic headache represents a significant scientific finding and clinical progress, as it implies that this kind of treatment can be effectively delivered in a hospital setting.

Altered functional connectivity between the insula and the cingulate cortex in patients with temporomandibular disorder: A pilot study

Abstract: Background.- Among the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3-15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain. Objective.- The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain. The current study sought specifically to investigate IC-CC functional connectivity in TMD patients and healthy controls (HCs), both during resting state and during the application of a painful stimulus. Methods.- Eight patients with TMD, and 8 age- and sex-matched HCs were enrolled in the present study. Functional magnetic resonance imaging data during resting state and during the performance of a pressure pain stimulus to the temple were acquired. Predefined seed regions were placed in the IC (anterior and posterior insular cortices) and the extracted signal was correlated with brain activity throughout the whole brain. Specifically, we were interested whether TMD patients and HCs would show differences in IC-CC connectivity, both during resting state and during the application of a painful stimulus to the face. Results.- As a main finding, functional connectivity analyses revealed an increased functional connectivity between the left anterior IC and pregenual anterior cingulate cortex (ACC) in TMD patients, during both resting state and applied pressure pain. Within the patient group, there was a negative correlation between the anterior IC-ACC connectivity and clinical pain intensity as measured by a visual analog scale. Conclusions.- Since the pregenual region of the ACC is critically involved in antinociception, we hypothesize that an increase in anterior IC-ACC connectivity is indicative of an adaptation of the pain modulatory system early in the chronification process. (Less)

Head Pain Referral During Examination of the Neck in Migraine and Tension-Type Headache

Abstract: Objective.-To investigate if and to what extent typical head pain can be reproduced in tension-type headache (TTH), migraine without aura sufferers, and controls when sustained pressure was applied to the lateral posterior arch of C1 and the articular pillar of C2, stressing the atlantooccipital and C2-3 segments respectively. Background.-Occipital and neck symptoms often accompany primary headache, suggesting involvement of cervical afferents in central pain processing mechanisms in these disorders. Referral of head pain from upper cervical structures is made possible by convergence of cervical and trigeminal nociceptive afferent information in the trigemino-cervical nucleus. Upper cervical segmental and C2-3 zygapophysial joint dysfunction is recognized as a potential source of noxious afferent information and is present in primary headache sufferers. Furthermore, referral of head pain has been demonstrated from symptomatic upper cervical segments and the C2-3 zygapophysial joints, suggesting that head pain referral may be a characteristic of cervical afferent involvement in headache. Methods.-Thirty-four headache sufferers and 14 controls were examined interictally. Headache patients were diagnosed according the criteria of the International Headache Society and comprised 20 migraine without aura (females n = 18; males n = 2; average age 35.3 years) and 14 TTH sufferers (females n = 11; males n = 3; average age 30.7 years). Two techniques were used specifically to stress the atlantooccipital segments (Technique 1 - C1) and C2-3 zygapophysial joints (Technique 2 - C2). Two techniques were also applied to the arm - the common extensor origin and the mid belly of the biceps brachii. Participants reported reproduction of head pain with "yes" or "no" and rated the intensity of head pain and local pressure of application on a scale of 0 -10, where 0 = no pain and 10 = intolerable pain. Results.-None of the subjects reported head pain during application of techniques on the arm. Head pain referral during the cervical examination was reported by 8 of 14 (57%) control participants, all TTH patients and all but 1 migraineur (P <.002). In each case, participants reported that the referred head pain was similar to the pain they usually experienced during TTH or migraine. The frequency of head pain referral was identical for Techniques 1 and 2. The intensity of referral did not differ between Technique 1 and Technique 2 or between groups. Tenderness ratings to thumb pressure were comparable between the Techniques 1 and 2 when pressure was applied to C1 and C2 respectively and across groups. Similarly, there were no significant differences for tenderness ratings to thumb pressure between Technique 1 and Technique 2 on the arm or between groups. While tenderness ratings to thumb pressure for Technique 2 were similar for both referral (n = 41) and non-referral (n = 7) groups, tenderness ratings for Technique 1 in the referral group were significantly greater when compared with the non-referral group (P =.01). Conclusions.-Our data support the continuum concept of headache, one in which noxious cervical afferent information may well be significantly underestimated. The high incidence of reproduction of headache supports the evaluation of musculoskeletal features in patients presenting with migrainous and TTH symptoms. This, in turn, may have important implications for understanding the pathophysiology of headache and developing alternative treatment options.

Migraine headaches and suicide attempt.

Abstract: (Headache 2012;52:723-731) Background.— Previous cross-sectional studies reported an increased risk of suicide attempt in persons with migraine headache, which was sustained when psychiatric comorbidity was statistically controlled. Objective.— To estimate the risk of suicide attempt in persons with migraine vs controls with no history of severe headache, using prospective data and validated diagnostic assessment. To examine the specificity of the migraine-suicide attempt risk by comparing it to the risk associated with non-migraine headache of comparable severity and disability. Methods.— A cohort of persons with migraine (n = 496), non-migraine severe headaches (n = 151), and controls with no history of severe headache (n = 539) was randomly selected from the general community, assessed in 1997 and reassessed 2 years later. Results.— Persons with migraine had an increased risk of suicide attempt during the 2-year follow-up period, compared with controls. Odds ratio, adjusted for sex, psychiatric disorder, and previous history of suicide attempt at baseline was 4.43 (95% confidence interval [CI] 1.93, 10.2). Persons with non-migraine headache of comparable intensity and disability also had an increased risk of suicide attempt, compared to controls: odds ratio, adjusted for the same covariates, was 6.20 (95% CI 2.40, 16.0). The difference between the 2 estimates was not significant. In the entire sample, headache severity at baseline predicted suicide attempt: a difference of 1 standard deviation (SD) in pain score increased the risk of suicide attempt by 79%, adjusting for sex and psychiatric disorders. Conclusions.— The results suggest the possibility that pain severity might account in part for the increased risk of suicide attempt associated with migraine.

Nociceptive Neuropeptide Increases and Periorbital Allodynia in a Model of Traumatic Brain Injury

Abstract: Long-term disability from traumatic brain injury (TBI) is prevalent occurring in approximately 3.17 million persons on an annual basis.1 Among the long-term consequences of TBI, post-traumatic headache (PTH) disorder represents the most common chronic pain syndrome within this patient population.2–7 PTH disorders are highly prevalent across all grades of TBI severity.8 Mild and moderate TBI is more prevalent compared to severe cases of TBI; however, there is a current controversy surrounding epidemiologic reports that cite a higher incidence of PTH for mild TBI compared with moderate and severe cases. A recent prospective 12-month study of TBI patients provides compelling evidence that the prevalence of PTH is unrelated to injury severity.9 Important aspects of PTH to consider relate to the time-course of this disorder. In many patients, it resolves in 3 months; in others, it persists for much longer. Currently, PTH, as classified by the International Classification of Headache Disorders, is defined as headache secondary to head trauma that develops within 7 days after injury or regaining consciousness. TBI is a risk factor for acute episodic headache (headache occurring less than 15 days/month) persisting less than 3 months transitioning into chronic headache (≥15 days/month).10,11 Clinical evidence suggest that the persistence of PTH beyond the expected tissue-healing time-course would argue for its chronicity, as well as mechanisms of central sensitization.12–14 A recent prospective study found the onset of PTH occurred between 7 and 30 days after injury or later in nearly half of patients.15 A study by Ofek and Defrin found that patients with TBI had a mean onset of chronic pain, including head pain, just over 6 months after injury.14 Headache was reported at 3, 6, and 12 months in 41% of patients with TBI in a study by Hoffman and colleagues.9 Studies using quantitative sensory testing (eg, von Frey mechanical stimuli for allodynia [cutaneous sensitivity to mechanical stimuli that are innocuous under normal conditions]) show that 40% of patients with TBI experience chronic head and face pain after head injury.14,16 Significant reductions in pressure-pain thresholds were found at least 1 year after mild-to-moderate TBI.16 To date, investigations into the proposed mechanisms and treatments for PTH have been impeded by a lack of preclinical models. Therefore, a research initiative implemented by our laboratory is to study mechanisms of PTH and its chronification using a well-known animal model of TBI, controlled cortical impact (CCI) injury. Headache pain, whether acute or chronic, involves abnormal activation of the trigeminovascular system. Using a model of diffuse TBI, Hall and Lifshitz have characterized hypersensitivity of the whiskers to be associated with neuroplasticity in the cortical barrel circuit and thalamus.17 Peripheral axons of the trigeminal ganglion innervate the peri-orbital skin, facial whiskers, anterior scalp, meninges, and cerebral vasculature. Periorbital and facial allodynia have been well-documented in rodent migraine models following infusion of an inflammatory soup over the meninges.18–20 Afferent fibers of the trigeminal ganglia relay nociceptive information to the trigeminal nuclei in which the neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), play important roles. CGRP and SP are also important in normal physiologic and pathologic function including cerebrovascular regulation and the development of neurogenic inflammation.21–26 CGRP has been particularly well-studied for its role in primary headache disorders such as migraine.27,28 To date, preclinical studies examining allodynia and the potential role of CGRP and SP in PTH are nonexistent. This study aimed to characterize periorbital sensory changes to mechanical stimuli (allodynia) and neuroplasticity in the brainstem in a mouse model of TBI, as this has not yet been reported in any model of TBI. The present study tests the hypothesis that focal injury to the somatosensory cortex will be associated with increased neuropeptides within the brainstem trigeminal nucleus caudalis and periorbital allodynia in a mouse model of CCI injury. The time-course for macrophage/microglial and astrocyte responses in the somatosensory cortex after CCI were examined because these cell populations are a potential cellular source of mediators (eg, cytokines, nitric oxide [NO], excitatory amino acids) of nociceptor sensitization known to contribute to behavioral morbidity. The pattern of periorbital allodynia over 4 weeks in mice with CCI and those undergoing a craniotomy only was characterized, while changes in the nociceptive neuropeptides, CGRP, and SP within the brainstem were determined. The temporal relationships between periorbital sensory changes (allodynia), central nociceptive neuropeptides, and gliosis (macrophage/microglia and astrocyte activation) were examined.

Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others.

Abstract: Objectives.— This second portion of a 3-part series examines the relative effectiveness of headache treatment with neuroleptics, antihistamines, serotonin antagonists, valproate, and other drugs (octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine) in the setting of an emergency department, urgent care center, or headache clinic. Methods.— MEDLINE was searched using the terms “migraine” AND “emergency” AND “therapy” OR “treatment.” Reports were from emergency department and urgent care settings and involved all routes of medication delivery. Reports from headache clinics were only included if medications were delivered by a parenteral route. Results.— Prochlorperazine, promethazine, and metoclopramide, when used alone, were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also have more side effects (especially akathisia). Metoclopramide was equivalent to prochlorperazine and, when combined with diphenhydramine, was superior in efficacy to triptans and non-steroidal anti-inflammatory drugs. Meperidine was inferior to chlorpromazine and equivalent to the other neuroleptics. The overall percentage of patients with pain relief after taking droperidol and prochlorperazine was equivalent to sumatriptan. Conclusions.— Prochlorperazine and metoclopramide are the most frequently studied of the anti-migraine medications in the emergent setting, and the effectiveness of each is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in producing migraine pain relief. Dopamine antagonists, in general, appear to be equivalent for migraine pain relief to the migraine-“specific” medications sumatriptan and dihydroergotamine, although there are fewer studies involving the last two. Lack of comparisons to placebo and the frequent use of combination medications in treatment arms complicate the comparison of single agents to one other.

Adverse childhood experiences are associated with migraine and vascular biomarkers.

Abstract: Objectives.—Migraine is a risk factor for stroke in young women. Biomarker studies implicate endothelial activation as a possible mechanism. Emerging relationships of childhood adversity with migraine, and with inflammation, a component of endothelial activation, suggest that it may play a role in the migraine–stroke association. Our objective is to evaluate the relationship between adverse childhood experiences (ACEs), migraine, and vascular biomarker levels in premenopausal women. Methods.—Vascular and metabolic biomarkers from women 18-50 years, including 125 with migraine (interictal) and 50 without migraine, were evaluated. An ACE questionnaire was later collected by mail (response rate 80.6%, 100 migraineurs, 41 controls). Results.—Migraineurs and controls were demographically similar. Migraineurs reported adversity more commonly than controls (71% vs 46%, odds ratio [OR] = 1.53, 95% confidence interval 1.07-2.17). Average ACE scores were elevated in migraineurs as compared with controls (2.4 vs 0.76, P < .001). ACE scores correlated with headache frequency (0.37, P = .001) and younger age of headache onset (-0.22,P = .04). It also correlated with body mass index (r = 0.43,P = .0001), von Willebrand factor activity (r = 0.21, P = .009), tissue plasminogen activator antigen (r = 0.28, P = .004), prothrombin activation fragment (r = 0.36,P = .001), high-sensitivity C-reactive protein (r = 0.98,P = .0001), transforming growth factor-beta1 (r = 0.28,P = .003), tissue necrosis factor-alpha (r = 0.20, P = .03), interleukin-6 (r = 0.22, P = .03), adiponectin (r =- 0.29, P = .003), and nitrate/ nitrite concentration (r =- 314, P = .001). Logistic regression analyses (adjusted for vascular risk factors and migraine) demonstrated an association of childhood adversity with inflammatory factors (high-sensitivity C-reactive protein, interleukin-6, and tissue necrosis factor-alpha).

Migraine: maladaptive brain responses to stress.

Abstract: Migraine offers a unique model to understand the consequences of repeated stressors on the brain. Repeated stressors can alter the normal response of physiological systems, and this concept has been termed "allostatic load." In the case of the brain, the effects of repeated stress may lead to alteration in brain networks both functionally and structurally. As a result, the brain responds abnormally to environmental conditions (psychological or physiological). Here, we present an alternative perspective on migraine disease and propose that changes in brain states may occur as a result of repeated migraine attacks through maladaptive coping mechanisms. The cascade of these effects can lead to further deterioration of adaptation and thus lead to transformation or chronification of the disease.

Rescue Therapy for Acute Migraine, Part 1: Triptans, Dihydroergotamine, and Magnesium

Abstract: Objective.— To review and analyze published reports on the acute treatment of migraine headache with triptans, dihydroergotamine (DHE), and magnesium in emergency department, urgent care, and headache clinic settings. Methods.— MEDLINE was searched using the terms “migraine” and “emergency,” and “therapy” or “treatment.” Reports from emergency department and urgent care settings that involved all routes of medication delivery were included. Reports from headache clinic settings were included only if medications were delivered by a parenteral route. Results.— Acute rescue treatment studies involving the triptans were available for injectable and nasal sumatriptan, as well as rizatriptan. Effectiveness varied widely, even when the pain-free and pain-relief statistics were evaluated separately. As these medications are known to work best early in the migraine, part of this variability may be attributed to the timing of triptan administration. Multiple studies compared triptans with anti-emetics, dopamine antagonists, and non-steroidal anti-inflammatory drugs. The overall percentage of patients with pain relief after taking sumatriptan was roughly equivalent to that recorded with droperidol and prochlorperazine. Sumatriptan was equivalent to DHE when only paired comparisons were performed. While the data extracted suggest that magnesium may be effective in treating all symptoms in patients experiencing migraine with aura across all migraine patients, its effectiveness seems to be limited to treating only photophobia and phonophobia. Conclusions.— Although there are relatively few studies involving health-care provider-administered triptans or DHE for acute rescue, they appear to be equivalent to the dopamine antagonists for migraine pain relief. The relatively rare inclusion of a placebo arm and the frequent use of combination medications in active treatment arms complicate the comparison of single agents with each other.

Migraine: Possible Role of Shear-Induced Platelet Aggregation With Serotonin Release

Abstract: Background.— Migraine patients are at an increased risk for stroke, as well as other thromboembolic events. This warrants further study of the role of platelets in a proportion of migraine patients. Objective.— To extend the “platelet hypothesis” using literature data and observations made in a rat model of shear stress-induced platelet aggregation. Such aggregation causes release of serotonin, leading to vasoconstriction during sufficiently strong aggregation and to long-lasting vasodilation when aggregation diminishes. This vasodilation also depends on nitric oxide and prostaglandin formation. Results.— A role for platelet aggregation in a number of migraineurs is indicated by reports of an increased platelet activity during attacks and favorable effects of antiplatelet medication. We hypothesize that in those patients, a migraine attack with or without aura may both be caused by a rise in platelet-released plasma serotonin, albeit at different concentration. At high concentrations, serotonin may cause vasoconstriction and, consequently, the neuronal signs of aura, whereas at low concentrations, it may already stimulate perivascular pain fibers and cause vasodilation via local formation of nitric oxide, prostaglandins, and neuropeptides. Platelet aggregation may be unilaterally evoked by elevated shear stress in a stenotic cervico-cranial artery, by reversible vasoconstriction or by other cardiovascular abnormality, eg, a symptomatic patent foramen ovale. This most likely occurs when a migraine trigger has further enhanced platelet aggregability; literature shows that many triggers either stimulate platelets directly or reduce endogenous platelet antagonists like prostacyclin. Conclusion.— New strategies for migraine medication and risk reduction of stroke are suggested.

Headache disorders in children and adolescents: their association with psychological, behavioral, and socio-environmental factors.

Abstract: Objective.—This cross-sectional study on a randomly drawn population sample of children and adolescents (n = 3399; aged 9 to 15) aimed at the assessment of patterns of associations between psychosocial variables and primary headache disorders like migraine (MIG) or tension-type headache. A headache-free group served as a control. Methods.—Data on headache and psychological trait variables (eg, internalizing symptoms), behavioral factors (eg, physical activities), and socio-environmental factors (eg, life events) were gathered by questionnaire. Logistic regression analyses were conducted with headache types (MIG, tension-type, and non-classifiable headache) as dependent variables. Results.—The pattern of correlations was largely congruent between the headache disorders. Associations were closest regarding maladaptive psychological traits (in particular internalizing symptoms with an odds ratio > 4 regarding MIG) compared with socio-environmental factors and particularly the behavioral factors. Unfavorable psychological traits and socio-environmental strains demonstrated distinctly stronger associations with MIG than tension-type headache and explained more variance in the occurrence of pediatric headache disorders than parental headache. Sex-specific analyses showed similarities as well as differences regarding the correlations, and in general, the associations were stronger in girls than boys. Conclusions.—A common path model as posited by several researchers in the field may explain the parallelism in biopsychosocial vulnerability regarding the different headache disorders.

Opioids Should Not Be Used in Migraine

Abstract: Opioids should not be used for the treatment of migraine. This brief review explores why not. Alternative acute and preventive agents should always be explored. Opioids do not work well clinically in migraine. No randomized controlled study shows pain-free results with opioids in the treatment of migraine. Saper and colleagues' 5-year study showed minimal effectiveness, with many contract violations, interfering with the therapeutic alliance. The physiologic consequences of opioid use are adverse, occur quickly, and can be permanent. Decreased gray matter, release of calcitonin gene-related peptide, dynorphin, and pro-inflammatory peptides, and activation of excitatory glutamate receptors are all associated with opioid exposure. Opioids are pro-nociceptive, prevent reversal of migraine central sensitization, and interfere with triptan effectiveness. Opioids precipitate bad clinical outcomes, especially transformation to daily headache. They cause disease progression, comorbidity, and excessive health care consumption. Use of opioids in migraine is pennywise and pound foolish.

A Population-Based Longitudinal Community Study of Major Depression and Migraine

Abstract: Objective To examine whether major depressive episodes (MDEs) are associated with an increased risk of migraine in the general population and to examine whether migraine is associated with an increase risk of MDE. Background Population-based cross-sectional studies have consistently reported an association between migraine and depression. However, longitudinal studies about this potentially bidirectional association are inconsistent. Methods This retrospective cohort study used 12 years of follow-up data from the Canadian National Population Health Survey (15,254 respondents, age >12). Stratified analysis, logistic regression, and proportional hazard modeling were used to quantify the effect of migraine on subsequent MDE status and vice versa. Results After adjusting for sex, age, and other chronic health conditions, respondents with migraine were 60% more likely (HR 1.6, 95% confidence interval 1.3-1.9) to develop MDE compared with those without migraine. Similarly adjusting for sex and age, respondents with MDE were 40% more likely (HR 1.4, 95% confidence interval 1.0-1.9) to develop migraine compared with those without MDE. However, the latter association disappeared after adjustment for stress and childhood trauma. Conclusions The current study provides substantial evidence that migraine is associated with the later development of MDEs, but does not provide strong causal evidence of an association in the other direction. Environmental factors such as childhood trauma and stress may shape the expression of this bidirectional relationship; however, the precise underlying mechanisms are not yet known.

Spontaneous trigeminal allodynia in rats: a model of primary headache.

Abstract: Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.

Dihydroergotamine, Ergotamine, Methysergide and Sumatriptan - Basic Science in Relation to Migraine Treatment

Abstract: The 5-hydroxytryptamine (5-HT) receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5-HT 1B, 5-HT1D, and 5-HT1F receptors. Ergotamine, dihydroergotamine, and methysergide, as well as the "triptan" sumatriptan, are all agonists for these receptors. The receptor profile and degree of selectivity of these four drugs differ, which is reflected by their side effects that limit their use in the acute and prophylactic treatment of migraine. The acute antimigraine efficacy of these remedies is very much dependent on the formulation used where, in general, parenteral formulations are more effective in reliving the symptoms of a migraine attack.

Self-Reported Comorbid Pains in Severe Headaches or Migraines in a US National Sample

Abstract: Aims.— To compare prevalence of self-reported comorbid temporomandibular joint muscle disorder-type, neck, back, and joint pains in people with severe headache or migraine; and analyze these self-reported pains in the 2000-2005 US National Health Interview Survey by gender and age for non-Hispanic whites, Hispanics, and non-Hispanic blacks (African Americans). Methods.— National Health Interview Survey data included information on gender, age, race, ethnicity, health status, and common pain types: severe headache or migraine, temporomandibular joint muscle disorder-type, neck, and low back in the last 3 months, as well as prior-month joint pains. Analyses included survey prevalence estimation and survey logistic regression to obtain odds ratios and 95% confidence intervals. Results.— The study included 189,967 adults: 48% males, 52% females; 73% white, 12% Hispanic, and 11% black. Of the entire sample, 29,712 (15%) reported severe headache or migraine, and 19,228 (64%) had severe headache or migraine with at least 1 comorbid pain. Two or more comorbid pains were reported in 10,200 (33%), with no gender difference, and with Hispanics (n = 1847 or 32%) and blacks (n = 1301 or 30%) less likely to report 2 or more comorbid pains than whites (n = 6747 or 34%) (odds ratio = 0.91, P = .032; OR = 0.82, P < .001, respectively). This group also reported significantly lower ratings of self-rated health (P < .001). Differences in type of comorbid pain by age patterns were found. Conclusions.— Severe headache or migraine is often associated with other common pains, seldom existing alone. Two or more comorbid pains are common, similarly affecting gender and racial/ethnic groups.

In medication-overuse headache, fMRI shows long-lasting dysfunction in midbrain areas.

Abstract: Objective. The primary aim of our study was to evaluate if a group of medication-overuse headache (MOH) patients present dysfunctions in the mesocorticolimbic dopamine circuit. The secondary aim was to disentangle the role of the medication overuse and of the acute/chronic headache in determining these alterations and to investigate their persistence. Background. Several researches have suggested that MOH may belong to the spectrum of addictive behavior. Preclinical models and neuroimaging studies have consistently demonstrated that in addiction, critical long-lasting alterations occur in the mesocorticolimbic dopamine circuit. If MOH shares some neurophysiological features with addiction, long-lasting functional alterations of the mesocorticolimbic dopamine system related to medication overuse should be present. Methods. We collected functional magnetic resonance imaging data during the execution of a decision-making under risk paradigm in 8 MOH patients immediately after beginning medication withdrawal, in 8 detoxified MOH patients at 6 months after beginning medication withdrawal, in 8 chronic migraine patients, and in 8 control subjects. Results. Our results revealed that MOH patients present: (1) reduced task-related activity in the substantia nigra/ventral tegmental area complex and increased activity in the ventromedial prefrontal cortex, when compared with controls; (2) reduced activity in the substantia nigra/ventral tegmental area complex, when compared with chronic migraine patients; (3) increased activity in the ventromedial prefrontal cortex, when compared with detoxified MOH patients. Conclusion. Our study showed that MOH patients present dysfunctions in the mesocorticolimbic dopamine circuit, in particular in the ventromedial prefrontal cortex and in the substantia nigra/ventral tegmental area complex. The ventromedial prefrontal cortex dysfunctions seem to be reversible and attributable to the acute/chronic headache, whereas the substantia nigra/ventral tegmental area complex dysfunctions are persistent and possibly related to medication overuse. These dysfunctions might be the expression of long-lasting neuroadaptations related to the overuse of medications and/or a pre-existing neurophysiological condition leading to vulnerability to medication overuse. The observed persistent dysfunctions in the midbrain dopamine suggest that MOH may share some neurophysiological features with addiction.