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Headache Disorders (headache + disorders)

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Selected Abstracts

Evidence of shared genetic risk factors for migraine and rolandic epilepsy

EPILEPSIA, Issue 11 2009
Tara Clarke
Summary Purpose:, Evidence for a specific association between migraine and rolandic epilepsy (RE) has been conflicting. Children with migraine frequently have electroencephalographic (EEG) abnormalities, including rolandic discharges, and approximately 50% of siblings of patients with RE exhibit rolandic discharges. We assessed migraine risk in RE probands and their siblings. Methods:, We used cohort and reconstructed cohort designs to respectively assess the relative risk of migraine in 72 children with RE and their 88 siblings using International Classification of Headache Disorders (ICHD-2) criteria. Incidences were compared in 150 age and geographically matched nonepilepsy probands and their 188 siblings. We used a Cox proportional hazards model, using age as the time base, adjusting hazard ratios (HRs) for sex in the proband analysis, and for sex and proband migraine status in the sibling analysis. Results:, Prevalence of migraine in RE probands was 15% versus 7% in nonepilepsy probands, and in siblings of RE probands prevalence was 14% versus 4% in nonepilepsy siblings. The sex-adjusted HR of migraine for an RE proband was 2.46 [95% confidence interval (CI) 1.06,5.70]. The adjusted HR of having ,1 sibling with migraine in an RE family was 3.35 (95% CI 1.20,9.33), whereas the HR of any one sibling of a RE proband was 2.86 (95% CI 1.10,7.43). Discussion:, Migraine is strongly comorbid in RE and independently clusters in their siblings. These results suggest shared susceptibility to migraine and RE that is not directly mediated by epileptic seizures. Susceptibility gene variants for RE may be tested as risk factors for migraine. [source]

Research Submission: Chronic Headache and Comorbibities: A Two-Phase, Population-Based, Cross-Sectional Study

HEADACHE, Issue 8 2010
Ariovaldo Da Silva Jr MD
Background., Studies using resources of a public family health program to estimate the prevalence of chronic daily headaches (CDH) are lacking. Objectives., To estimate the 1-year prevalence of CDH, as well as the presence of associated psychiatric and temporomandibular disorders (TMD) comorbidities, on the entire population of a city representative of the rural area of Brazil. Methods., This was a cross-sectional, population-based, 2-phase study. In the first phase, health agents interviewed all individuals older than 10 years, in a rural area of Brazil. In the second stage, all individuals who reported headaches on 4 or more days per week were then evaluated by a multidisciplinary team. CDH were classified according to the second edition of the International Classification of Headache Disorders (ICHD-2). Medication overuse headache was diagnosed, as per the ICHD-2, after detoxification trials. Psychiatric comorbidities and TMD were diagnosed based on the DSM-IV and on the Research Diagnostic Criteria for Temporomandibular Disorders criteria, respectively. Results., A total of 1631 subjects participated in the direct interviews. Of them, 57 (3.6%) had CDH. Chronic migraine was the most common of the CDH (21, 36.8%). Chronic tension-type headache (10, 17.5%), medication overuse headache (13, 22.8%) and probable medication overuse headache (10, 17.5%) were also common. Psychiatric disorders were observed in 38 (67.3%) of the CDH subjects. TMD were seen in 33 (58.1)% of them. Conclusions., The prevalence of CDH in the rural area of Brazil is similar to what has been reported in previous studies. A significant proportion of them have psychiatric comorbidities and/or TMD. In this sample, comorbidities were as frequent as reported in convenience samples from tertiary headache centers. (Headache 2010;50:1306-1312) [source]

Migraine in Adolescents: Validation of a Screening Questionnaire

HEADACHE, Issue 2 2009
Luca Valentinis MD
Background., Few studies in adolescents deal with the level of agreement between questionnaire and interview information in relation to headache symptoms. Objective., To evaluate the validity of a self-administered questionnaire on headache for use in epidemiological studies of Italian high school students. Methods., The questionnaire incorporated all items required for diagnosing migraine according to the criteria from the 2004 International Classification of Headache Disorders. The migraine diagnoses obtained from questionnaires were validated against the gold standard diagnoses by a headache specialist. Results., Out of 104 students answering the questionnaires, 93 (89.4%) participated in extensive semi-structured interviews by a neurologist. The chance-corrected agreement rate (kappa) was 0.66, which is considered good. The questionnaire-based migraine diagnosis had a sensitivity of 67.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 73.3%. Conclusions., The results indicate that our self-administered questionnaire may be an acceptable instrument in determining the prevalence of migraine sufferers in the northeast Italy adolescent population, useful in identifying subjects with "definite" migraine. [source]

Migraine Disability Awareness Campaign in Asia: Migraine Assessment for Prophylaxis

HEADACHE, Issue 9 2008
Shuu-Jiun Wang MD
Objectives., This study aimed to survey the headache diagnoses and consequences among outpatients attending neurological services in 8 Asian countries. Methods., This survey recruited patients who consulted neurologists for the first time with the chief complaint of headache. Patients suffering from headaches for 15 or more days per month were excluded. Patients answered a self-administered questionnaire, and their physicians independently completed a separate questionnaire. In this study, the migraine diagnosis given by the neurologists was used for analysis. The headache symptoms collected in the physician questionnaire were based on the diagnostic criteria of migraine proposed by the International Classification of Headache Disorders, second edition (ICHD-2). Results., A total of 2782 patients (72% females; mean age 38.1 ± 15.1 years) finished the study. Of them, 66.6% of patients were diagnosed by the neurologists to have migraine, ranging from 50.9% to 85.8% across different countries. Taken as a group, 41.4% of those patients diagnosed with migraine had not been previously diagnosed to have migraine prior to this consultation. On average, patients with migraine had 4.9 severe headaches per month with 65% of patients missing school, work, or household chores. Most (87.5%) patients with migraine took medications for acute treatment. Thirty-six percent of the patients had at least one emergency room consultation within one year. Only 29.2% were on prophylactic medications. Neurologists recommended pharmacological prophylaxis in 68.2% of patients not on preventive treatment. In comparison, migraine prevalence was the highest with ICHD-2 "any migraine" (ie, migraine with or without migraine and probable migraine) (73.3%) followed by neurologist-diagnosed migraine (66.6%) and ICHD-2 "strict migraine" (ie, migraine with or without aura only) (51.3%). About 88.6% patients with neurologist-diagnosed migraine fulfilled ICHD-2 any migraine but only 67.1% fulfilled the criteria of ICHD-2 strict migraine. Conclusions., Migraine is the most common headache diagnosis in neurological services in Asia. The prevalence of migraine was higher in countries with higher referral rates of patients to neurological services. Migraine remains under-diagnosed and under-treated in this region even though a high disability was found in patients with migraine. Probable migraine was adopted into the migraine diagnostic spectrum by neurologists in this study. [source]

Functional Imaging in Primary Headache Disorders

HEADACHE, Issue 5 2008
F. Michael Cutrer MD
Over the past two decades, the development of new functional neuroimaging techniques has improved our understanding of the brain events underlying several primary headache disorders. In migraine and cluster headache, the advent of these techniques has shifted the emphasis in pathophysiological research away from the vessel and back to the brain. [source]

Sleep and Headache Disorders: Clinical Recommendations for Headache Management

HEADACHE, Issue 2006
Jeanetta C. Rains PhD
Clinical practice points were drawn from a review of sleep and headache disorders published in the regular issue of Headache (released in tandem with this supplement). The recommendations include: (1) Sleep as well as psychiatric disorders tend to become prevalent in more complex and severe headache patterns and regulation of sleep and mood may favorably impact headache threshold; (2) Specific headache patterns, irrespective of headache diagnosis, are suggestive of a potential sleep disorder (eg, "awakening" or morning headache, chronic daily headache); (3) Sleep disorders most implicated with headache include obstructive sleep apnea, primary insomnia, and circadian phase abnormalities, and treatment of such sleep disorders may improve or resolve headache; (4) Inexpensive screening tools (eg, sleep history interview, headache/sleep diary, validated questionnaires, prediction equations) aid identification of patients warranting polysomnography; and (5) Pharmacologic and behavioral therapies are effective in the regulation of sleep and are compatible with usual headache care. [source]

From Hemicrania Lunaris to Hemicrania Continua: An Overview of the Revised International Classification of Headache Disorders

HEADACHE, Issue 7 2004
Jonathan P. Gladstone MD
The International Headache Society's (IHS) Classification of Headache Disorders, published in 1988, is largely responsible for stimulating the rapid scientific and therapeutic advances that have revolutionized the field of headache. By establishing consistent operational diagnostic criteria for primary and secondary headache disorders, the IHS Classification has facilitated epidemiological and genetic studies as well as the multinational clinical trials that provide the basis for our present treatment guidelines. Fifteen years after its original release, a revised 2nd edition has been unveiled. Modifications are small but significant. We hope to introduce clinicians to the salient changes in the 2nd edition by highlighting the newly included headache types, acknowledging the renamed headache types, and reviewing the modifications in diagnostic criteria for existing headache types. Physicians involved in the care of headache patients need to be aware of these changes and should continue to consult the IHS criteria to ensure accurate diagnosis, to continue to refine the diagnostic criteria, and to contribute to the body of knowledge necessary to make further advances in the classification as well as in the field of headache. [source]

Botulinum Neurotoxin for the Treatment of Migraine and Other Primary Headache Disorders: From Bench to Bedside

HEADACHE, Issue 2003
David W. Dodick MD
Botulinum toxin type A, a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction including cervical dystonia, blepharospasm, and hemifacial spasm. It inhibits neuromuscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient, with normal neuronal signaling returning within approximately 3 to 6 months postinjection. Recent clinical findings suggest that botulinum toxin type A may inhibit pain associated with migraine and other types of headache. However, the mechanism by which this toxin inhibits pain is not fully understood and is under investigation. Research findings suggest that botulinum toxin type A inhibits the release of neurotransmitters from nociceptive nerve terminals and, in this way, may possess an analgesic effect. A number of retrospective open-label chart reviews and 3 double-blind, placebo-controlled trials have demonstrated that localized injections of botulinum toxin type A significantly reduce the frequency, severity, and disability associated with migraine headaches. Although the majority of patients in these studies experienced no botulinum toxin type A-mediated side effects, a small percentage of patients did report transient minor side effects including blepharoptosis, diplopia, and injection-site weakness. Currently, 4 randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A as a novel treatment for migraine and other types of headache. These studies may provide further evidence that botulinum toxin type A is an effective option for the preventive treatment of migraine. [source]

A Prospective Controlled Study in the Prevalence of Posttraumatic Headache Following Mild Traumatic Brain Injury

PAIN MEDICINE, Issue 8 2008
S. Faux FAFRM (RACP) FFPMANZCA
ABSTRACT Objective., To establish the prevalence of post traumatic headache, persisting at 3 months following minor traumatic brain injury. Design., A prospective controlled study of patients admitted with a diagnosis of mild traumatic brain injury and matched orthopedic controls over 12 months during 2004. Setting., A level two inner city Emergency Department in Sydney, Australia. Patients., One hundred eligible sequential admissions with mild traumatic brain injury as defined by American Congress of Rehabilitation Medicine, 1993, and 100 matched minor injury controls with nondeceleration injuries. Interventions., Subjects were part of a study on prediction of postconcussive syndrome and had neuropsychological tests, balance test and pain recordings taken at the time of injury, at 1 month and at 3 months post injury. Outcome Measures., Main measures were the reporting of headache "worse than prior to the injury" and concordant with the definition of Posttraumatic Headache according to International Headache Society Classification of Headache Disorders 2003. Results., 15.34% of those with minor head injury continued to complain of perisistant posttraumatic headache at 3 months compared to 2.2% of the minor injury controls. Conclusions., To the authors' knowledge this is the first controlled prospective study in the prevalence of posttraumatic headache following mild traumatic brain injury. [source]

What is chronic headache in the general population?

ACTA NEUROLOGICA SCANDINAVICA, Issue 2009
The Akershus study of chronic headache
Background ,, Studies of chronic headache including both primary and secondary causes from the general population is lacking. Aims ,, To provide prevalence data on chronic headache. Materials & Methods ,, We studied chronic headaches defined as headache 15 days per month on average for at least 3 months in the general population. An age and gender stratified random sample of 30,000 persons aged 30,44 years received a mailed questionnaire. Those with self-reported headache on 15 days or more within the last month and/or headache on more than 180 days within the last year were invited to an interview and examination by a neurological resident. The criteria of the International Classification of Headache Disorders were applied. Results ,, Chronic headache occurred in 3.71% of the general population.Women had chronic headache twice as often as men. About half of those with chronic headache also had medication overuse, irrespectively of the types of chronic headache. Secondary chronic headaches attributed to chronic rhinosinusitis, head injury, whiplash injury and cervicogenic headache were relatively frequent, i.e. from 1 of 300 to 1 of 600 persons from the general population. Discussion ,, Primary and secondary chronics headaches should not be ignored. Conclusion ,, Primary and secondary chronic headaches are common in the general population. [source]

Melatonin therapy for headache disorders

DRUG DEVELOPMENT RESEARCH, Issue 6 2007
Mario F.P. Peres
Abstract Even though efficacy is often the most important consideration for patient preference in migraine prevention, currently available medications do not meet patient expectation. Efficacy is in the range of 50% reduction in migraine attacks in 50% of patients studied for the best medications. Therefore, new options for migraine treatment are needed. Melatonin has been considered a good candidate for migraine and other headaches prevention due to its favorable mechanisms of action and excellent tolerability profile. In this article, we review the putative role of the pineal gland and melatonin in migraine pathophysiology and treatment. Drug Dev Res 68:329,334, 2007. © 2007 Wiley-Liss, Inc. [source]

Neurophysiological tests and neuroimaging procedures in non-acute headache: guidelines and recommendations

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2004
G. Sandrini
The use of instrumental examinations in headache patients varies widely. In order to evaluate their usefulness, the most common instrumental procedures were evaluated, on the basis of evidence from the literature, by an EFNS Task Force (TF) on neurophysiological tests and imaging procedures in non-acute headache patients. The conclusions of the TF regarding each technique are expressed in the following guidelines for clinical use. 1Interictal electroencephalography (EEG) is not routinely indicated in the diagnostic evaluation of headache patients. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic and basilar migraine. 2Recording of evoked potentials is not recommended for the diagnosis of headache disorders. 3There is no evidence to justify the recommendation of autonomic tests for the routine clinical examination of headache patients. 4Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pressure algometry and electromyography (EMG) cannot be recommended as clinical diagnostic tests. 5In adult and paediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological signs or symptoms, the routine use of neuroimaging is not warranted. In patients with atypical headache patterns, a history of seizures and/or focal neurological signs or symptoms, magnetic resonance imaging (MRI) may be indicated. 6If attacks can be fully accounted for by the standard headache classification [International Headache Society (IHS)], a positron emission tomography (PET) or single-photon emission computerized tomography (SPECT) and scan will generally be of no further diagnostic value. 7Nuclear medicine examinations of the cerebral circulation and metabolism can be carried out in subgroups of headache patients for diagnosis and evaluation of complications, when patients experience unusually severe attacks, or when the quality or severity of attacks has changed. 8Transcranial Doppler examination is not helpful in headache diagnosis. Although many of the examinations described are of little or no value in the clinical setting, most of the tools have a vast potential for further exploring the pathophysiology of headaches and the effects of pharmacological treatment. [source]

Diagnosis and Treatment of the Menstrual Migraine Patient

HEADACHE, Issue 2008
Stephen D. Silberstein MD
Women presenting with recurrent disabling headache frequently have migraine; but physicians need to rule out other headache disorders before they reach a diagnosis of migraine with or without aura. Many women who experience migraine in close association to their menstrual cycle may meet the diagnostic criteria for either menstrually related migraine (MRM), or pure menstrual migraine (PMM). Once an accurate diagnosis is made, treatment may be established to best suit the individual needs of that patient. Most women will find that migraine associated with hormone fluctuations respond well to standard treatment approaches including pharmacological and nonpharmacological treatments. Pharmacological approaches include acute, preventive, and short-term prophylaxis. Herein we review the difference between non-menstrual migraine, PMM, and MRM and identify effective treatment strategies for appropriate management of migraine associated with hormonal fluctuations. [source]

Headache Progress in Canada Over the Decades

HEADACHE, Issue 5 2008
Werner J. Becker MD
As elsewhere in the world, migraine and other headache disorders have always produced very significant disability amongst Canadians. Over the last 50 years, progress has been made by health professionals to improve the care received by patients with headache, and to reduce the headache-related burden carried by patients and their families. Milestones in this progress have included programs for better education for the public, for neurologists, and for other physicians about migraine. Highlights in the Canadian battle against migraine and other headaches include those listed below: [source]

Functional Imaging in Primary Headache Disorders

Headache as a Real Disease

HEADACHE, Issue 5 2008
Richard B. Lipton MD
Acceptance of headache disorders as "real diseases" is now widespread due largely to advances made over the last 50 years in diagnoses, treatment, and the understanding of pathophysiology. Drs. Lipton and Bigal examine the path to acceptance and the impediments that had to be overcome. [source]

A Retrospective, Comparative Study on the Frequency of Abuse in Migraine and Chronic Daily Headache

HEADACHE, Issue 3 2007
B. Lee Peterlin DO
Objective.,To assess and contrast the relative frequency of a past history of physical and/or sexual abuse in patients with chronic daily headache (CDH) versus migraine. Background.,A number of risk factors have been identified as risk factors for chronification of headache disorders. Limited data exist regarding the influence of physical and/or sexual abuse on primary headache disorders. Methods.,This was a retrospective chart review of 183 consecutive new headache patients seen from December 2004 through August 2005 at an outpatient tertiary-care center. Patients were included in the study if they had chronic daily headache (with criteria for medication over-use headache or chronic migraine), or migraine with or without aura. A history of physical and/or sexual abuse was systematically asked of all headache patients at their first visit in the clinic. This information was then transferred to a semi-standardized form and the relative frequency of abuse in both groups contrasted. Results.,Of the 161 patients included in the study, 90.1% were female with a mean age of 36.4 ± 12.0. A total of 59.0% of the patients were diagnosed with CDH and 41.0% were diagnosed with migraine. Overall, 34.8% of all patients, 40.0% of CDH patients, and 27.3% of migraine patients had a history of physical and/or sexual abuse. The relative frequency of a history of physical and/or sexual abuse was higher in the CDH group as compared to the migraine group (P= .048). Conclusion.,The relative frequency of abuse is higher in CDH sufferers than migraineurs, suggesting that physical and sexual abuse may be risk factors for chronification. [source]

Sleep and Headache Disorders: Clinical Recommendations for Headache Management

From Hemicrania Lunaris to Hemicrania Continua: An Overview of the Revised International Classification of Headache Disorders

Understanding the Patient With Migraine: The Evolution From Episodic Headache to Chronic Neurologic Disease.

HEADACHE, Issue 5 2004
A Proposed Classification of Patients With Headache
Traditionally, episodic primary headache disorders are characterized by a return of preheadache (normal) neurologic function between episodes of headache. In contrast, patients with chronic headache often do not return to normal neurologic function between headache attacks. This article proposes that the evolution from episodic migraine to chronic headache may parallel the neurologic disruption observed during the progression of an acute migraine attack and that changes in baseline neurologic function between episodes of headache may be a more sensitive indicator of headache transformation than headache frequency alone. Early recognition of nonheadache changes in nervous system function may offer a more sensitive and specific approach to migraine prevention. [source]

Application of the 1988 International Headache Society Diagnostic Criteria in Nine Italian Headache Centers using a Computerized Structured Record

HEADACHE, Issue 10 2002
Virgilio Gallai MD
Background.,The actual application of the current International Headache Society (IHS) diagnostic criteria in clinical practice has not been investigated thoroughly. Objectives.,To develop a computerized, structured, medical record based exclusively on the IHS classification system. Design and Method.,We tested the computerized structured record by entering and analyzing data reported on the case sheets of 500 consecutive patients attending nine headache centers in Italy. All clinical diagnoses in the study were made according to current IHS criteria. The rate of concordance between the diagnosis provided by the computerized structured record and that reported by clinicians on the case sheets was calculated, and reasons for any discrepancies between the two diagnoses were analyzed. Results.,Concordance between the two diagnoses was found in 345 of 500 cases examined (69%). In the remaining 155 cases, diagnoses reached with the computerized structured record and case sheets were impossible or discordant with respect to the diagnoses made by the clinician. In 144 of these cases (28.8%), this was due to missing information or errors in the diagnosis recorded by the clinicians on the patient case sheet. In particular, the diagnosis could not be reached using the computerized structured record in 105 cases (20.6%) because of a lack of one or more data needed in formulating a correct diagnosis according to the IHS operational criteria for one of the primary headache disorders. In the remaining 41 cases some data were missing, but the data available were sufficient to reach a diagnosis according to the IHS criteria. Moreover, the diagnoses reached using the computerized structured record were not in agreement with those made by the clinicians in another 39 cases (7.9%) due to an incorrect interpretation by the clinicians of the data reported on the patients' case sheets. In only 2.2% of the cases (n = 11) misdiagnoses were due to errors of the program that were promptly corrected. Conclusions.,The present study suggests that incorrect application of IHS criteria for the diagnosis of primary headache may occur in as many as one third of patients attending headache centers and that use of a computerized structured record based exclusively on current IHS criteria may overcome this deficiency. [source]

Lifetime Prevalence and Characteristics of Recurrent Primary Headaches in a Population-Based Sample of Swedish Twins

HEADACHE, Issue 8 2002
Dan A. Svensson MSc
Objective.,To examine the lifetime prevalence and other characteristics of recurrent primary headaches in twins. Background.,The twin model may provide insights into the role of genetic and environmental influences in headache disorders. However, assumptions as to whether twins are representative of the general population, and whether monozygotic and dizygotic twins are similar have rarely been addressed. Methods.,The study population consisted of a random sample of 17- to 82-year-old twins from the Swedish Twin Registry (n = 1329). Structured interviews on the telephone by lay personnel and the International Headache Society criteria were used for assessment and diagnosis of recurrent primary headaches. Prevalence data of the general population for migraine and tension-type headache was obtained from various published reports. Results.,A total of 372 subjects (29%) had ever had recurrent headaches. In total, 241 recurrent headache sufferers fulfilled the criteria for migraine or tension-type headache, and the lifetime prevalence was 7.1% for migraine without aura, 1.4% for migraine always with aura, 1.9% for migraine occasionally with aura, 9.4% for episodic tension-type headache, and 1.3% for chronic tension-type headache. The lifetime prevalence of all migraine and all tension-type headache, including another 84 subjects fulfilling all but one of the criteria for migraine or tension-type headache, was 13.8% and 13.5%, respectively. The corresponding prevalence risk for women was 2.4 (95% confidence interval [CI] 1.7, 3.4) and 1.5 (95% CI 1.1, 2.1), respectively. Zygosity was not a significant predictor for migraine. In tension-type headache, the prevalence risk for dizygotic twins and unlike-sexed twins as compared with monozygotic twins was 1.9 (95% CI: 1.2, 3.1) and 1.8 (95% CI: 1.1, 2.9), respectively. Conclusion.,There is no twin-singleton or monozygotic-dizygotic difference for the risk of migraine. In tension-type headache, twins seem to have a lower risk than singletons, and this is especially true for monozygotic twins. [source]

Medullary pain facilitating neurons mediate allodynia in headache-related pain,

ANNALS OF NEUROLOGY, Issue 2 2009
Rebecca M. Edelmayer BS
Objective To develop and validate a model of cutaneous allodynia triggered by dural inflammation for pain associated with headaches. To explore neural mechanisms underlying cephalic and extracephalic allodynia. Methods Inflammatory mediators (IM) were applied to the dura of unanesthetized rats via previously implanted cannulas, and sensory thresholds of the face and hind-paws were characterized. Results IM elicited robust facial and hind-paw allodynia, which peaked within 3 hours. These effects were reminiscent of cutaneous allodynia seen in patients with migraine or other primary headache conditions, and were reversed by agents used clinically in the treatment of migraine, including sumatriptan, naproxen, and a calcitonin gene,related peptide antagonist. Consistent with clinical observations, the allodynia was unaffected by a neurokinin-1 antagonist. Having established facial and hind-paw allodynia as a useful animal surrogate of headache-associated allodynia, we next showed that blocking pain-facilitating processes in the rostral ventromedial medulla (RVM) interfered with its expression. Bupivacaine, destruction of putative pain-facilitating neurons, or block of cholecystokinin receptors prevented or significantly attenuated IM-induced allodynia. Electrophysiological studies confirmed activation of pain-facilitating RVM "on" cells and transient suppression of RVM "off" cells after IM. Interpretation Facial and hind-paw allodynia associated with dural stimulation is a useful surrogate of pain associated with primary headache including migraine and may be exploited mechanistically for development of novel therapeutic strategies for headache pain. The data also demonstrate the requirement for activation of descending facilitation from the RVM for the expression of cranial and extracranial cutaneous allodynia, and are consistent with a brainstem generator of allodynia associated with headache disorders. Ann Neurol 2009;65:184,193 [source]