Chronification Of Headache Research Articles

Medication overuse headache: a review of current evidence and management strategies.

The third edition of the International Classification of Headache Disorders (ICHD-3) defines medication-overuse headache (MOH) as a headache that develops when a person regularly uses acute or symptomatic headache medications excessively (10 or more, or 15 or more days per month, depending on the medication) for a period of time longer than 3 months. Even though it may not be reported as frequently as it actually is, it affects about 5% of the general population on average. It typically happens following repeated anti-pain medication use for pre-existing headache disorders, such as migraines. Anti-pains can also be used frequently in patients with pre-existing headache disorders for reasons other than treating headaches, such as psychological drug attachment. MOH is linked to a number of illnesses, such as anxiety, depression, and obsessive compulsive disorder (OCD). Both simple and complex types are possible. Additionally, there is no universal consensus on how to treat MOH, but drug discontinuation is the best course of action. Using the medical subject headings "Medication Overuse Headache," "Migraine Headache," "Tension Headache," "Chronification of Headache," and "Antipains," an all-language literature search was done on PubMed, Google Scholar, and Medline up until March 2023. We looked into the epidemiology, risk factors, pathophysiology, clinical characteristics, comorbidities, diagnosis, management, and preventative measures of MOH in the literature. This article focuses on the MOH research themes.

Analysis of the implementation of the collaboration programme between the headache unit and the liaison psychiatry programme

Introduction Headache is associated with a wide spectrum of comorbid, statistically and biologically related pathological processes. A person with headache is more likely to have a psychological disorder than the rest of the general population, even more so if the headache is chronic. Psychiatric comorbidity has been shown to act as a risk factor in the chronification of headache and may contribute to increased disability. Anxiety and mood disorders are the psychiatric comorbidities that most influence aspects of the disease such as prognosis, response to treatment and even quality of life.ObjectivesTo analyse the results of the implementation of a joint consultation between the headache unit and the liaison psychiatry programme.To evaluate the efficacy of interdisciplinary intervention in patients diagnosed with resistant headache.Methods We performed a descriptive analysis of the database of patients included in the headache programme including data on neurological diagnosis, psychiatric diagnosis, type of intervention, referral to psychiatric consultation and number of subsequent revisions.ResultsDiagnoses related to anxious and depressive symptomatology are the most common diagnoses in patients diagnosed with treatment-resistant headache.In most of the patients analysed in the database a single joint intervention was necessary.Referral to mental health consultations from the programme did not lead to an increase in urgent demands with a clinical correlation in terms of diagnostic orientationConclusionsJoint intervention in the management of these patients has been found to be beneficial in the reinterpretation of symptoms and progressive desensitisation to fear of chronic illness.Training in symptom detection at the psychopathological level is important for professionals from other areas as well as training in interviewing skills.More studies are needed to analyse the outcome of joint interventions in patients with difficult-to-manage chronic diseases and their comorbidities.Disclosure of InterestNone Declared

Medication-overuse Headache: Diagnostic Criteria, Epidemiology, and Treatment

Regular and frequent use of acute or symptomatic medications can worsen headaches and cause chronification of headache or medication-overuse headache (MOH). Although MOH is a burdensome medical condition because of disability in individual and socioeconomic aspects, difficulty in treatment, and frequent recurrence, even epidemiologic research is insufficient. Educating patients, general population, and healthcare providers about MOH is important in the first step to reducing the burden of MOH. In addition, preventing the occurrence of MOH is essential for the management of patients with a primary headache disorder. Physicians should educate and counsel the patients with MOH to stop or at least reduce the intake of acute or symptomatic medications. Withdrawal symptoms such as headache, nausea, and vomiting can be manageable with the bridging therapy using steroid or anti-emetic agents during or after the discontinuation of the overused medications. The promising efficacy of botulinum toxin A and calcitonin gene-related peptide monoclonal antibodies in the treatment of MOH have been published in the past few years. Evidencebased preventive therapies might be helpful in patients with MOH for both discontinuation of the overused medication and prevention of relapse. A comprehensive and multidisciplinary approach would improve the outcome for patients with MOH.

Post-traumatic Headache: Pharmacologic Management and Targeting CGRP Signaling.

Post-traumatic headache is a common sequela of injury to the head and/or neck. Here, we review the current approach to pharmacologic management of post-traumatic headache and explore the therapeutic promise of targeting calcitonin gene-related peptide signaling to address unmet treatment needs. The scarcity of data from controlled trials has left clinicians to rely on mainly expert opinion for the pharmacologic management of post-traumatic headache. The current view is that a phenotype-guided approach should be used, in which patients are treated according to the primary headache phenotype that their clinical features resemble the most (e.g. migraine, tension-type headache). Moreover, incremental advances are being made in the field that aim to identify possible cellular and molecular drivers of headache persistence. Calcitonin gene-related peptide has emerged as a key drug target which, in turn, has prompted novel insights on the potential importance of early initiation of pharmacologic treatment following the onset of post-traumatic headache. This, in turn, might prevent subsequent persistence and chronification of headache.

Contributions of aversive environmental stress to migraine chronification: Research update of migraine pathophysiology.

Clinical studies have suggested that internal and/or external aversive cues may produce a negative affective-motivational component whereby maladaptive responses (plasticity) of dural afferent neurons are initiated contributing to migraine chronification. However, pathophysiological processes and neural circuitry involved in aversion (unpleasantness)-producing migraine chronification are still evolving. An interdisciplinary team conducted this narrative review aimed at reviewing neuronal plasticity for developing migraine chronicity and its relevant neurocircuits and providing the most cutting-edge information on neuronal mechanisms involved in the processing of affective aspects of pain and the role of unpleasantness evoked by internal and/or external cues in facilitating the chronification process of migraine headache. Thus, information presented in this review promotes the understanding of the pathophysiology of chronic migraine and contribution of unpleasantness (aversion) to migraine chronification. We hope that it will bring clinicians’ attention to how the maladaptive neuroplasticity of the emotion brain in the aversive environment produces a significant impact on the chronification of migraine headache, which will in turn lead to new therapeutic strategies for this type of pain.

The impact of parental attitudes toward children with primary headaches.

There is a lack of data on parental attitudes toward children with primary headaches. The aim of this study is to determine whether there is a relationship between primary headaches and parental attitudes in the pre-adolescent pediatric population. In this cross-sectional study, 195 children with primary headache and 43 healthy children aged 9-16 years were included. A questionnaire for sociodemographic variables, visual analog scale (VAS), Social Anxiety Scale and Depression Inventory for Adolescents and Children, and Parental Attitudes Determining Scale (PATS), which is an attitude measure specifically designed to evaluate psychological adjustment, were administered. Of 195 children (female/male ratio: 89/106, mean age: 12.59 ± 1.09 years), episodic migraine (n = 90), chronic migraine (n = 25), and tension-type headache (n = 80) were evaluated. There was no significant difference among headache groups and healthy subjects in terms of depression, anxiety, and fathers' attitude scale scores. However, there were significant differences in mean mothers' attitude scale scores and VAS scores (p = .002, p = .000). Mean oppressive-authoritarian attitude subscale scores of mothers' was significantly higher in children with chronic migraine (p = .000). A relationship between depression and VAS scores among all patient groups was detected (p = .000). Parental age was negatively related to PATS scores of children with episodic migraine and tension-type headache (p = .037 and p = .036). Parental attitudes may elevate psychiatric symptoms and influence children's perception of pain intensity and result in chronification of headache. Our findings support that mothers' attitude toward children with chronic migraine has strong impacts on the child's pain experience.

Pathophysiology of Headaches

Pathophysiological concepts of primary headache diseases have been developed significantly in the last decades. Nevertheless pathophysiology of single diseases is unexplained. Migraine headache arises from activation and sensibilization of trigeminal nociceptors, essential processes are located at the meninges and the meningeal vessels. Calcitonin gene-related peptide (CGRP) seems to have essential importance concerning migraine and cluster headache. Mechanisms leading to peripheral and central sensitization are relevant inchronification of migraine and tension-type headache. Asahigher-level centre the hypothalamus seems to have an essential meaning in the initiation of migraine attacks. Dysbalance between the sympathetic and parasympathetic neural system causes cranial-autonomic symptoms in some headache diseases and can be affected therapeutically.

Clinical and Demographical Characteristics of Patients with Medication Overuse Headache in Argentina and Chile: Analysis of the Latin American Section of COMOESTAS Project.

BackgroundData on the characteristics of Medication Overuse Headache (MOH) in Latin American (LA) are scarce. Here we report the demographic and clinical features of the MOH patients from Argentina and Chile enrolled in the multinational COMOESTAS project in the period 2008–2010.MethodsThe LA population was formed by 240 MOH subjects, 110 from Chile and 130 from Argentina, consecutively attending the local headache centres. In each centre, specifically trained neurologist interviewed and confirmed the diagnosis according to the ICHD-II criteria. A detailed history was collected on an electronic patient record form.ResultsThe mean patient age was 38.6 years, with a female/male ratio of 8:2. The mean time since onset of the primary headache was 21 years, whereas duration of MOH was 3.9 years. The primary headache was migraine without aura in 77.5 % and migraine with aura in 18.8 %. Forty two % of the patients self-reported emotional stress associated with the chronification of headache; 43.8 % reported insomnia. The most overused medications were acute drug combinations containing ergotamine (70 %), NSAIDs (33.8 %) and triptans (5.4 %).ConclusionThough little described, MOH is present also in LA, where it affects mostly women, in the most active decades of life. Some differences emerge as regards the demographic and clinical characteristics of MOH in this population as compared to Europe or Northern America. What seems more worrying about MOH in Argentina and Chile is that most patients overuse ergotamine, a drug that may cause serious adverse events when used chronically. These findings once more underscore the importance of properly diagnose and treat MOH.

Potential risk of dihydroergotamine causing medication- overuse headache: preclinical evidence

Background: Overuse of abortive medication is a common factor contributing to an increase in headache frequency in patients with migraine. Whether or not chronic exposure to dihydroergotamine (DHE) can lead to this transformation remains uncertain. Objective: To determine the effect of acute and chronic DHE exposure on development of cortical spreading depression (CSD) and trigeminal nociception. Methods: The study comprised two experiments, namely acute and chronic exposure. In the acute experiment, a single dose of DHE (100 μg/kg) was given to male Wistar rats after successful induction of CSD. In the chronic experiment, DHE was given daily for the period of 0, 7, 14, and 28 days. CSD was induced 30 minutes after the final injection and the cortical field potential was recorded. Expression of c-Fos in caudal brainstem was used as an indicator of trigeminal nociception. Results: Acute exposure to DHE attenuated the expression of c-Fos in the caudal brainstem without change in CSD response. By contrast, chronic exposure (14 and 28 days) to DHE increased the area under the curve of CSD waveforms. In parallel with the change in the CSD, there was significant increase of c-Fos expression within 14 days exposure to DHE and the expression remained significantly elevated for up to the 28 days examined. Conclusion: Our study demonstrated that chronic DHE administration can increase cortical excitability and increase c-Fos expression in caudal brainstem. Our preclinical evidence suggests the possible adverse effect of chronic DHE use in causing chronification of headache.

Original article. Potential risk of dihydroergotamine causing medicationoveruse headache: preclinical evidence

Abstract Background: Overuse of abortive medication is a common factor contributing to an increase in headache frequency in patients with migraine. Whether or not chronic exposure to dihydroergotamine (DHE) can lead to this transformation remains uncertain. Objective: To determine the effect of acute and chronic DHE exposure on development of cortical spreading depression (CSD) and trigeminal nociception. Methods: The study comprised two experiments, namely acute and chronic exposure. In the acute experiment, a single dose of DHE (100 μg/kg) was given to male Wistar rats after successful induction of CSD. In the chronic experiment, DHE was given daily for the period of 0, 7, 14, and 28 days. CSD was induced 30 minutes after the final injection and the cortical field potential was recorded. Expression of c-Fos in caudal brainstem was used as an indicator of trigeminal nociception. Results: Acute exposure to DHE attenuated the expression of c-Fos in the caudal brainstem without change in CSD response. By contrast, chronic exposure (14 and 28 days) to DHE increased the area under the curve of CSD waveforms. In parallel with the change in the CSD, there was significant increase of c-Fos expression within 14 days exposure to DHE and the expression remained significantly elevated for up to the 28 days examined. Conclusion: Our study demonstrated that chronic DHE administration can increase cortical excitability and increase c-Fos expression in caudal brainstem. Our preclinical evidence suggests the possible adverse effect of chronic DHE use in causing chronification of headache.

Chronic headaches and insomnia: Working toward a biobehavioral model

Sleep disturbances are consistently associated with chronic headaches, yet the mechanisms underlying this relationship remain unclear. One potential barrier to generating new hypotheses is the lack of synthesis between models of headache and models of sleep. The goal of this paper is to present a perspective on the chronification of migraine and tension-type headaches based upon conceptual models used in sleep research. We provide a critical review of the literature on sleep and headache, highlighting the limitations in sleep methodology. Models of sleep physiology and insomnia are discussed, along with the potential implications for the chronification of migraine and tension-type headache. In addition, we propose a biobehavioral model that describes the interaction between behaviors related to coping with headache, the impact of these behaviors on insomnia and sleep physiology and the downstream propensity for future headache attacks. We hope that this perspective will stimulate interdisciplinary activity toward uncovering the pathway for more effective interventions for chronic headache patients.

Pathophysiology of Medication-overuse Headache: Implications from Animal Studies

Recent animal experiments have shown that chronic medication exposure profoundly affects the function of several areas in the nervous system related to headache pathogenesis. These changes include upregulation of calcitonin gene-related peptide, substance P, and nitric oxide synthase in trigeminal ganglia; expansion of receptive field and decreased nociceptive threshold of central trigeminal neurons; decrease in diffuse noxious inhibitory control; and increased susceptibility to develop cortical spreading depression (CSD). These changes indicate an increase in excitability of cortical and trigeminal neurons. The neuronal hyperexcitability may be the result of derangement of a central, possibly serotonin (5-HT)-dependent, modulating control system. Experiments with animals with low 5-HT showed that the processes of CSD and trigeminal nociception are enhanced in this condition. Derangement in the central 5-HT-dependent modulating system as a result of chronic medication use may underlie the chronification of headache as observed in patients with medication-overuse headache.

Headache characteristics and chronification of migraine and tension-type headache: A population-based study

Migraine and tension-type headache (TTH) can increase in frequency and transform from episodic to chronic forms. The process of transformation of these primary headaches is complex and involves multiple risk factors. In this cross-sectional and longitudinal population study, we aimed to investigate the relation of clinical characteristics of primary headaches to poor outcome: new-onset or persistent chronic headache (> or =180 days/year). Individuals who had migraine + / - TTH and those who had pure TTH were studied separately. Of 740 individuals who entered this study in 1989, 673 were eligible for follow-up in 2001, and a total of 549 individuals participated in the follow-up study. At baseline in 1989, no difference was found between episodic and chronic migraine headache ( + / - TTH). Duration of headache episodes >72 hours (p = .002) was associated with pure chronic TTH at baseline in 1989 whereas aggravation of headache by physical activity (p = .045) was associated with pure frequent episodic TTH. Of 64 subjects with migraine + / - TTH, 12 had a poor outcome in 2001. For pure TTH, of 116 subjects at baseline, 11 had a poor outcome in 2001. Using multivariate logistic regression analysis with adjustment for medication overuse and use of preventive medications, poor outcome of migraine + / - TTH tended to be associated with a baseline pulsating quality and severe intensity of migraine, photophobia and phonophobia, as well as longer duration of an individual headache attack. For pure TTH, unilateral headache, nausea and individual headache attack duration greater than 72 hours was associated with poor outcome. Pooled data univariate analysis revealed that nausea, daily use of acute headache medications, use of headache preventive medications and coexistent headaches were significant predictors of chronic headache in 2001(p<.05). In conclusion, our study demonstrates that certain clinical characteristics of headaches are associated with poor outcome but alone may not predict the chronification of migraine or TTH.

Obsessive‐Compulsive Disorder and Migraine With Medication‐Overuse Headache

A strong association has been demonstrated between migraine, particularly in the chronic form and with medication overuse, and either major depression or various anxiety disorders. However, there has been less systematic research on the links between migraine with medication-overuse headache (MOH) and obsessive-compulsive disorder (OCD). A drug-seeking behavior shares with OCD the compulsive quality of the behavior. We investigated the relationship between OCD and MOH in migraineurs. A structured questionnaire was administered to subjects with: episodic migraine (EM) (n = 30), chronic migraine (CM) (n = 24), and MOH with a previous history of EM (n = 33) and 29 control subjects. Psychiatric diagnoses were made by a senior psychiatrist blinded to the diagnosis of migraine. Psychiatric assessment of OCD illness was evaluated by means of The Yale-Brown Obsessive Compulsive Scale (Y-BOCS). In the subgroup of patients with MOH, psychiatric comorbidity (anxiety and mood disorders) was prevalent compared with CM, EM, and controls (P < .0001). Subclinical OCD was significantly prevalent in MOH patients with respect to other groups (P < .0002). Higher scores in Y-BOCS, as a measure of severity of obsessive-compulsive symptoms, were found in both MOH and CM compared with controls and EM. The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and undertreated.

Adolescent issues in migraine: A focus on menstrual migraine

Migraine commonly affects adolescents, and menstrual migraine often begins in young girls. If undiagnosed or ineffectively treated, migraine can lead to disability, school absenteeism, emotional or social difficulties, and chronification of headache. Thus, recognizing and accurately diagnosing migraine and menstrual migraine, developing effective treatment strategies (both pharmacologic and nonpharmacologic), and educating both the adolescent and her parents are important in order to minimize the potential early disability of this disorder and limit the otherwise likely progression of migraine to a disabling disorder of adulthood.

Abnormal pain processing in chronic tension-type headache: a high-density EEG brain mapping study

Central sensitization caused by prolonged nociceptive input from muscles is considered to play an important role for chronification of tension-type headache. In the present study we used a new high-density EEG brain mapping technique to investigate spatiotemporal aspects of brain activity in response to muscle pain in 19 patients with chronic tension-type headache (CTTH) and 19 healthy, age- and sex-matched controls. Intramuscular electrical stimuli (single and train of five pulses delivered at 2 Hz) were applied to the trapezius muscle and somatosensory evoked potentials were recorded with 128-channel EEG both in- and outside a condition with induced tonic neck/shoulder muscle pain (glutamate injection into the trapezius muscle). Significant reduction in magnitude during and after induced tonic muscle pain was found in controls at the P200 dipole in response to both the first (baseline versus tonic muscle pain: P = 0.001; baseline versus post-tonic muscle pain: P = 0.002) and fifth (baseline versus tonic muscle pain: P = 0.04; baseline versus post-tonic muscle pain: P = 0.04) stimulus in the train. In contrast, there were no differences between the conditions in patients. No consistent difference was found in localization or peak latency of the dipoles. The reduction in magnitude during and after induced tonic muscle pain in controls but not in patients with CTTH may be explained by impaired inhibition of the nociceptive input in these patients. This may be the first evidence that the supraspinal response to muscle pain is abnormal in patients with CTTH.

Chronic Headache and Potentially Modifiable Risk Factors: Screening and Behavioral Management of Sleep Disorders

Sleep-related variables have been identified among risk factors for frequent and severe headache conditions. It has been postulated that migraine, chronic daily headache, and perhaps other forms of chronic headache are progressive disorders. Thus, sleep and other modifiable risk factors may be clinical targets for prevention of headache progression or chronification. The present paper is part of the special series of papers entitled "Chronification of Headache" describing the empirical evidence, future research directions, proposed mechanisms, and risk factors implicated in headache chronification as well as several papers addressing individual risk factors (ie, sleep disorders, medication overuse, psychiatric disorders, stress, obesity). Understanding the link between risk factors and headache may yield novel preventative and therapeutic approaches in the management of headache. The present paper in the special series reviews epidemiological research as a means of quantifying the relationship between chronic headache and sleep disorders (sleep-disordered breathing, insomnia, circadian rhythm disorders, parasomnias) discusses screening for early detection and treatment of more severe and prevalent sleep disorders, and discusses fundamental sleep regulation strategies aimed at headache prevention for at-risk individuals.

Introduction to the Special Series on the Chronification of Headache: Mechanisms, Risk Factors, and Behavioral Strategies Aimed at Primary and Secondary Prevention of Chronic Headache

The transformation or clinical progression of headache from episodic to “chronic daily headache” is a well-evidenced and long-recognized phenomenon. Citing several demonstrations of brain abnormalities in migraineurs (eg, brain infarction and white matter lesions, iron deposits in periaqueductal gray correlating with headache duration, central sensitization), Lipton and Pan suggested that clinical progression may be accompanied by progressive changes in the brain and that in some cases it could be conceptualized as a chronic progressive disorder. While migraine progresses in some patients, it does not progress in all or even most patients, leading Bigal and Lipton to conclude that migraine is best understood as a chronic disorder with episodic attacks and that it is progressive in some patients. The conceptualization of migraine, chronic daily headache, and perhaps eventually other forms of chronic headache, as sometimes progressive disorders highlights the importance of identifying potentially modifiable risk factors associated with onset and progression, screening and risk factor modification (primary prevention), and early intervention to limit progression (secondary prevention). Clear identification of such risk factors could provide a foundation for the development of preventive interventions. Some of the risk factors for headache chronification identified to date are nonmodifiable (eg, age, low socioeconomic status, head injury), other risk factors have a key behavioral component that can be recognized and modified. Thus, screening and behavioral risk-reduction (ie, behavioral self-management) strategies may serve to prevent chronification. Analgesic overuse is probably the most widely recognized and best empirically established risk factor associated Address all correspondence to Donald B. Penzien, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.

Stress and Headache Chronification

In this special section, the concept of stress has been linked to the chronification of headache and is considered to be one of several likely mechanisms for the progression of an otherwise episodic disorder to a chronic daily phenomenon. The present review discusses the concept of stress and describes the mechanisms through which stress could influence headache progression. The hypothesized mechanisms include stress serving as a unique trigger for individual attacks, as a nociceptive activator, and as a moderator of other mechanisms. Finally, the techniques used in the screening and management of stress are mentioned in the context of employing strategies for the primary, secondary, or tertiary prevention of headache progression.

Headache Chronification: Screening and Behavioral Management of Comorbid Depressive and Anxiety Disorders

A growing body of literature implicates comorbid psychopathology as a risk factor for chronification of headache. Despite their prevalence, comorbid psychiatric conditions are not routinely assessed among headache patients. Consequently, efforts to manage such conditions are not commonplace either. The present article briefly reviews a variety of strategies and measures for psychiatric screening among headache patients, focusing primarily on those that have been validated in medical settings, that can be administered quickly, and that involve minimal associated costs. We also describe basic strategies for behavioral management of comorbid depression and anxiety in headache patients.