Is headache a risk factor for dementia? A systematic review and meta-analysis.

OBJECTIVE: In this systematic review and meta-analysis, we critically evaluate available evidence regarding the association between primary headaches and subsequent decline of cognitive function and dementia. BACKGROUND: Recent studies suggested that headache disorders may increase the risk for dementia. However, available studies are conflicting. METHODS: To identify qualifying studies, we searched scientific databases, including Pubmed, Scopus, Web of Science, Science Direct and BMC, screening for relevant papers. In order to reduce the heterogeneity between different studies, the analyses were further subdivided according to the clinical diagnoses and the study methodologies. RESULTS: We identified 23 studies investigating the association between primary headaches and the risk of dementia. Of these, 18 met our inclusion criteria for meta-analysis (covering 924.140 individuals). Overall effect-size shows that primary headaches were associated with a small increase in dementia risk (OR = 1,15; CI 95%: 1,03-1,28; p = 0,02). Analyzing subgroups, we found that migraine was associated with both a moderate increased risk of all-cause dementia (OR = 1,26; p = 0,00; 95% CI: 1,13-1,40) as well as a moderate increased risk of Alzheimer's disease (OR = 2,00; p = 0,00; 95% CI: 1,46-2,75). This association was significant in both case-control and retrospective cohort studies but not in prospective studies. CONCLUSIONS: Our study supports the presence of a link between primary headaches and dementia. However, in the subgroup analysis, only patients with migraine showed a moderate increase risk for all-cause dementia and for Alzheimer's disease. Additional rigorous studies are needed to elucidate the possible role of primary headaches on the risk of developing cognitive impairment and dementia.

Subsume Pediatric Headaches in Psychiatric Disorders? Critiques on Delphic Nosology, Diagnostic Conundrums, and Variability in the Interventions.

PURPOSE OF REVIEW: Tension-type headache (TTH) continues to be the most prevalent type of headache across all age groups worldwide, and the global burden of migraine and TTH together account for 7% of all-cause years lived with disability (YLDs). TTH has been shown to have a prevalence of up to 80% in several studies and presents a wide range and high variability in clinical settings. The aim of this review is to identify gaps in diagnostics, nosology, and variability in the treatment of children and adolescents who present with headaches without an identifiable etiology. RECENT FINDINGS: Migraine and TTH have been debated to have more similarities than distinctions, increasing chances of misdiagnosis and leading to significant cases diagnosed as probable TTH or probable migraine. The lack of specificity and sensitivity for TTH classification often leads to the diagnosis being made by negating associated migraine symptoms. Although pathology is not well understood, some studies have suggested a neurological basis for TTH, in need of further validation. Some research indicates that nitric oxide signaling plays an integral part in the pain mechanisms related to TTH. Analgesics and non-steroidal anti-inflammatories are usually the first lines of treatment for children with recurring headaches, and additional treatment options include medication and behavioral therapies. With high prevalence and socioeconomic burden among children and adolescents, it's essential to further study Tension-type headaches and secondary headaches without known cause and potential interventions. Treatment studies involving randomized controlled trials are also needed to test the efficacy of various treatments further.

Vessel-wall MRI in primary headaches: The role of neurogenic inflammation.

OBJECTIVE: The purpose of this study was to investigate if vessel-wall magnetic resonance imaging (VW-MRI) could differentiate among primary headaches disorders, such as migraine and cluster headache (CH), and detect the presence of neurogenic inflammation. BACKGROUND: The pathophysiology of primary headaches disorders is complex and not completely clarified. The activation of nociceptive trigeminal afferents through the release of vasoactive neuropeptides, termed "neurogenic inflammation," has been hypothesized. VW-MRI can identify vessel wall changes, reflecting the inflammatory remodeling of the vessel walls despite different etiologies. METHODS: In this case series, we enrolled seven patients with migraine and eight patients with CH. They underwent a VW-MRI study before and after the intravenous administration of contrast medium, during and outside a migraine attack or cluster period. Two expert neuroradiologists analyzed the magnetic resonance imaging (MRI) studies to identify the presence of vessel wall enhancement or other vascular abnormalities. RESULTS: Fourteen out of 15 patients had no enhancement. One out of 15, with migraine, showed a focal parietal enhancement in the intracranial portion of a vertebral artery, unmodified during and outside the attack, thus attributable to atherosclerosis. No contrast enhancement attributable to neurogenic inflammation was observed in VW-MRI, both during and outside the attack/cluster in all patients. Moreover, MRI angiography registered slight diffuse vasoconstriction in one of seven patients with migraine during the attack and in one of eight patients with cluster headache during the cluster period; both patients had taken triptans as symptomatic therapy for pain. CONCLUSIONS: These preliminary results suggest that VW-MRI studies are negative in patients with primary headache disorders even during migraine attacks or cluster periods. The VW-MRI studies did not detect signs of neurogenic inflammation in the intracranial intradural vessels of patients with migraine or CH.

Are Morphometric Alterations of the Deep Neck Muscles Related to Primary Headache Disorders? A Systematic Review.

This systematic review aims to summarise the evidence from studies that examined morphometric alterations of the deep neck muscles using diagnostic imaging (ultrasound imaging, magnetic resonance imaging, and computed tomography) in patients diagnosed with primary headache disorders (PHD). No previous reviews have focused on documenting morphometric changes in this population. We searched five databases (up to 12 November 2022) to identify the studies. The risk of bias (RoB) was assessed using the Quality in Prognostic Studies (QUIPS) tool and the overall quality of the evidence was assessed using The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. A total of 1246 studies were screened and five were finally included; most were at high RoB, and the overall level of confidence in results was very low. Only two studies showed a significant association between morphometric alterations of the deep neck muscles and PHD (p < 0.001); nevertheless, their RoB was high. Contradictory and mixed results were obtained. The overall evidence did not show a clear association between morphometric alterations of the deep neck muscles in patients diagnosed with PHD. However, due to the limited number of studies and low confidence in the evidence, it is necessary to carry out more studies, with higher methodological quality to better answer our question.

Translation, cross-cultural adaptation and measurement proprieties of the German version of the Allodynia Symptom Checklist (ASC-12).

BACKGROUND: Cutaneous allodynia is highly prevalent among migraineurs and is associated with a poor prognosis. The Allodynia Symptom Checklist (ASC-12) is a comprehensive questionnaire to identify the presence and severity of allodynia. Our aim was to translate and adapt the ASC-12 to German and evaluate its measurement properties. METHODS: Following the COSMIN guidelines, 80 migraine patients were enrolled in the study to evaluate the stages of translation (n=30) and measurement propriety assessment (n=50), respectively. After reaching a final version, the German ASC-12 was assessed for structural validity, internal consistency, test-retest reliability, construct validity and absolute agreement, using mechanical and thermal pain thresholds as reference method. RESULTS: The German version of the ASC-12 presented an adequate structural validity compatible with the original version of the questionnaire. Its internal consistency ranged from 0.70 to 0.80 considering the total score and the thermic, static and dynamic mechanic subdomains. The total score presented excellent reliability (ICC: 0.85) with a standard error of measurement of 1.15 points and smallest detectable change of 3.40 points. ASC-12 total scores were correlated with headache intensity (r=0.38, p=0.004), headache disability (r=0.37, p=0.004) and cold pain thresholds (r=0.28, p=0.025). The thermic allodynia ASC-12 scores were correlated with cold (r=0.36, p=0.005) and heat (r=-0.30, p=0.010) pain thresholds, while the static mechanical allodynia ASC-12 scores correlated with mechanical pain threshold (r=0.29, p=0.019) and with mechanical pain sensitivity (r=0.24 to 0.28, p< 0.045). Despite no significant bias between methods, quantitative sensory testing (QST) results and ASC-12 scores tend to disagree. CONCLUSION: The German version of the ASC-12 is available for research and clinical settings and presented adequate measurement proprieties, as the original version. Despite the correlation between the ASC-12 and QST, one method cannot be replaced by the other.

The burden and health care use of patients with migraine and tension-type headache in post-conflict area of Serbia.

PURPOSE: The aim of the present study was to assess the burden and health care use of adult patients with migraine and tension type headache in a post-conflict area of Serbia. METHODS: This cross-sectional study was conducted on a representative sample of adults, living in predominantly Serb communities on the Kosovo and Metohija territory. The required data was obtained through a survey, utilizing a culturally-adapted questionnaire. The study sample comprised of 1,062 adults. RESULTS: In the year preceding the study, 49.7% of included subjects suffering from migraines and 27.5% of those experiencing tension type headache sought medical assistance for their condition. The majority (88.5%) of the respondents utilized non steroid antiinfammatory drugs as analgesic, while 14.2% used prophylactic treatment. Migraine sufferers reported losing on average 11.1 days in a 3-month period, while those experiencing tension type headache lost 4.7 days (p < 0.001) due to headaches, preventing them from partaking in professional, family and social activities. On headache-free days, 24.5% of the respondents were anxious or tense in anticipation of a headache onset, while 30% did not feel that the headache had completely resolved. Moreover, 11.5% of the sample reported never or rarely feeling in control of the headache, while 20% of the respondents were of view that their headaches were not taken seriously by their employer and co-workers and rarely discuss them. Adverse effect of headaches on education is more frequently noted by migraine sufferers than those experiencing tension type headache (p = 0.001), and this disparity persists in relation to career (p < 0.001) and family planning (p = 0.001). CONCLUSIONS: In Kosovo and Metohija, primary headaches exert a profound influence on the affected individuals and their community, and thus require recognition as one of the priorities of social initiatives aimed at the enhancement of public health.

Nasal airway obstruction and orofacial pain: a multicenter retrospective analysis.

The aim of this study was to investigate the relationship between nasal airway obstruction (NAO) and symptoms of orofacial pain, including temporomandibular joint pathology and primary headaches. This study was a retrospective analysis of consecutive patients seeking care for chronic orofacial pain at 14 North American treatment centers. The standardized evaluation protocol followed for all patients included cone beam computed tomography (CBCT), a comprehensive clinical examination, and a thorough review of the patient's subjective complaints and health history, including pain and sleep pathology. The primary conditions of interest in this study were the following 5 types of NAO: nasal valve compromise (NVC), deviated septum, septal swell body, concha bullosa, and inferior turbinate soft tissue hypertrophy. Descriptive statistics and regression analysis were performed to determine comorbidities between orofacial pain symptoms and NAO observed on CBCT images. The study population consisted of 1393 patients, 253 men (18.2%) and 1140 women (81.8%). The mean age of the patients was 43.3 (SD 18.1) years. NVC was the most prevalent type of NAO found in the study population (n = 1006; 72.2%). NVC showed a statistically significant comorbidity with capsulitis (odds ratio, 3.73) as well as facial and cervical myositis (odds ratio, 6.97). To the author's knowledge, this is first time that these comorbidities have been identified. NAO had a high comorbidity with orofacial pain. Specifically, NVC was a major contributor to NAO. An understanding of the mechanisms of orofacial pain as well as the effects of improper (mouth) breathing, adaptive forward head posture, muscular fatigue, parafunction, and temporomandibular joint pathology will help the clinician to evaluate the role a patient's nose may be playing in orofacial pain.

[Headaches in general medical practice].

The bulk of patients with primary headaches HA (cephalalgias) are observed in primary care. The optimal diagnostic algorithm implies the exclusion of potentially dangerous causes of HA and secondary cephalalgias requiring specific treatment. Verification of the form of primary HA is carried out clinically, does not require additional diagnostic methods and is based on the use of the criteria of the International Classification of Headache Disorders. Among all cephalalgias in general clinical practice, the vast majority of cases are represented by four forms: migraine, tension type headache, cluster headache, and medication overuse headache. The complex application of modern methods of pharmacological and non-pharmacological treatment with the use of preventive strategies ensures high efficiency in the management of patients with HA.

The first prevalence study of primary headaches in adults in a post-conflict area of Serbia.

AIM: The aim of the present study was to establish annual prevalence of primary headaches, migraine, and tension-type headache among adults in a post-conflict area of Serbia. METHODS: The data for this cross-sectional study was obtained via face-to-face interviews using questionnaires specifically designed for this purpose, in line with the available guidelines. The study sample included adults aged 18-65 years whose native language is Serbian with residence in six predominantly Serbian communities in Kosovo and Metohija. Relevant diagnoses were established according to the diagnostic criteria of the International Classification of Headache Disorders, 3rd edition. RESULTS: The study included 1062 adults. Analyses indicated 47.7% prevalence of primary headaches. The 1-year prevalence of migraine (with aura and without aura) and tension-type headache was established at 15.2% (3.3% and 11.9%), and 32.2%, respectively. One-year prevalence of chronic headache was calculated at 3.5%, while the prevalence of medication overuse headache was slightly lower at 2.9%. Primary headaches were more prevalent among women, participants residing south of the river Ibar, married or cohabiting individuals, as well as among interviewees (persons) who reported feeling unsafe in Kosovo and Metohija. This is the first study of the prevalence of primary headache disorders in Serbia. The obtained data is comparable to the data available for other countries, especially those in the Balkan region.

Self-perceived competence of dental students regarding the management of orofacial pain: a cross-sectional study.

BACKGROUND: There is limited data on Pakistani dental students perceived competence in managing orofacial pain (OFP). This study aims to evaluate dental students self-perceived competence regarding the management of orofacial pain. METHODS: This cross-sectional study was conducted in Karachi at randomly selected two public and four private dental schools. This survey was conducted online from November 2020 to December 2020 in six dental schools. A questionnaire link was sent to the 475 students. A chi-square test and independent-sample t-test were conducted to assess the frequency distribution and compare mean scores of knowledge, diagnosis, and management parameters. RESULTS: Of the 475 students, 280 students filled the online survey leaving a response rate of 59%. A significant number of fourth-year students, 65 (51%, p = 0.005), feels knowledgeable regarding neuropathic pain compared to third-year students. The majority of the fourth-year students, 100 (78%, p = 0.010), feel comfortable managing intraoral pain. Almost all the students reported thinking that they need more knowledge related to five types of OFP. The fourth-year students had high mean scores related to knowledge, comfort in diagnosing and managing OFP categories. CONCLUSION: This study found that dental students perceived competence regarding orofacial pain management varies in relation to specific categories, being lowest for psychogenic pain.

CGRP outflow into jugular blood and cerebrospinal fluid and permeance for CGRP of rat dura mater.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is released from activated meningeal afferent fibres in the cranial dura mater, which likely accompanies severe headache attacks. Increased CGRP levels have been observed in different extracellular fluid compartments during primary headaches such as migraine but it is not entirely clear how CGRP is drained from the meninges. METHODS: We have used an in vivo preparation of the rat to examine after which time and at which concentration CGRP applied onto the exposed parietal dura mater appears in the jugular venous blood and the cerebrospinal fluid (CSF) collected from the cisterna magna. Recordings of meningeal (dural) and cortical (pial) blood flow were used to monitor the vasodilatory effect of CGRP. In a new ex vivo preparation we examined how much of a defined CGRP concentration applied to the arachnoidal side penetrates the dura. CGRP concentrations were determined with an approved enzyme immunoassay. RESULTS: CGRP levels in the jugular plasma in vivo were slightly elevated compared to baseline values 5-20 min after dural application of CGRP (10 µM), in the CSF a significant three-fold increase was seen after 35 min. Meningeal but not cortical blood flow showed significant increases. The spontaneous CGRP release from the dura mater ex vivo was above the applied low concentration of 1 pM. CGRP at 1 nM did only partly penetrate the dura. CONCLUSIONS: We conclude that only a small fraction of CGRP applied onto the dura mater reaches the jugular blood and, in a delayed manner, also the CSF. The dura mater may constitute a barrier for CGRP and limits diffusion into the CSF of the subarachnoidal space, where the CGRP concentration is too low to cause vasodilatation.

ANALYSIS OF PRIMARY HEADACHES MANAGEMENT IN POLTAVA REGIONS.

OBJECTIVE: The aim: Assess quality of diagnosis and treatment of primary headaches (PH) in Poltava region. PATIENTS AND METHODS: Materials and methods: There were examined 195 patients with PH who were previously consulted by different specialists due to headaches. We analyzed previously established diagnoses, previous consultations and prescribed investigations due to headache, drugs that were prescribed for headache treatment. RESULTS: Results: The misdiagnoses of PH were made due to considering the headache as secondary (as sign of dyscirculatory encephalopathy, arterial hypertension, autonomic dysfunction, cervical ostheochondrosis). Patients older 40 years were misdiagnosed more often with dyscirculatory encephalopathy, while patients under 40 years were more frequently misdiagnosed with autonomic dysfunctions. Patients sought medical help for headache problem and were repeatedly examined by different specialists (general practitioner, neurologist, cardiologist, ophthalmologist, oyorhinolaryngologist, neurosurgeon). Doctors prescribed a large number of identical uninformative neuroimaging and neurofunctional methods regardless of PH nosologies. Also it had been often prescribed therapy with the use of vascular, metabolic, nootropic drugs without specific pathogenetic effects for PH. CONCLUSION: Conclusions: It is necessary to improve the diagnosis and treatment of PH according to international standards by raising awareness among general practitioners, neurologists and other specialists about the basics of PH diagnosis and treatment.

A prospective study on osmophobia in migraine versus tension-type headache in a large series of attacks.

BACKGROUND: In literature, osmophobia is reported as a specific migrainous symptom with a prevalence of up to 95%. Despite the International Classification of Headache Disorders 2nd edition proposal of including osmophobia among accompanying symptoms, it was no longer mentioned in the ICHD 3rd edition. METHODS: We conducted a prospective study on 193 patients suffering from migraine without aura, migraine with aura, episodic tension-type headache or a combination of these. After a retrospective interview, each patient was asked to describe in detail osmophobia, when present, in the following four headache attacks. RESULTS: In all, 45.7% of migraine without aura attacks were associated with osmophobia, 67.2% of migraineurs reported osmophobia in at least a quarter of the attacks. No episodic tension-type headache attack was associated with osmophobia. It was associated with photophobia or phonophobia in 4.3% of migraine without aura attacks, and it was the only accompanying symptom in 4.7% of migraine without aura attacks. The inclusion of osmophobia in the ICHD-3 diagnostic criteria would enable a 9.0% increased diagnostic sensitivity. CONCLUSION: Osmophobia is a specific clinical marker of migraine, easy to ascertain and able to disentangle the sometimes challenging differential diagnosis between migraine without aura and episodic tension-type headache. We recommend its inclusion among the diagnostic criteria for migraine as it increases sensitivity, showing absolute specificity.

Nummular headache: a gender-oriented perspective on a case series from the RegistRare Network.

BACKGROUND: Nummular headache (NH) is a rare headache disorder characterized by a small, circumscribed painful area of the scalp. The description of many cases in the last years has supported its re-classification as a primary headache from the International Headache Society, moving it from its previous placement in the Appendix of the International Criteria of Headache Disorders. METHODS: Data were collected from a retro-prospective observational study about rare headaches promoted by the RegistRare Network, a collaborative group of seven Italian Headache Centres. According to the gender-biased profile of certain primary headaches, we have looked further NH patients from a gender perspective. RESULTS: Nineteen NH patients (11 men, 8 women) have been enrolled in the study. Headache onset was at 39 years and preceded approximately 8 years the diagnosis. No clinically evident differences between men and women have been found, including treatment prescriptions and headache resolution. Of note, the mean time from the onset of NH to the first visit in a Headache Centre was longer in men, compared with women (13.5 vs. 0.9 years). NH attacks were efficaciously treated with nonsteroidal anti-inflammatory drugs in 60% of patients receiving treatment. Headache prophylaxis with pregabalin and amitriptyline has been reported as effective in 40% and 67% of the treated patients, respectively. CONCLUSIONS: NH is a primary headache clinically heterogeneous in terms of temporal patterns and pain characteristics. Further research is needed to investigate the existence of male and female phenotypes, by clarifying whether it may be relevant for therapeutic purposes.

A Study of Clinical Features and Risk Factors of Self-Referring Emergency Department Headache Patients: A Comparison with Headache Center Outpatients.

BACKGROUND: Nonlife-threatening headaches account for 3% of emergency department (ED) admissions, with social and economic negative consequences. We aim to investigate clinical features and risk factors of nonlife-threatening headache patients referring to ED versus those referring to headache outpatient clinics. METHODS: During 6 months, we promptly reevaluated in our headache unit (HU) patients discharged from ED. We compared the clinical characteristics of patients who referred to ED with those of HU outpatients visited in the same time interval. Discriminant Function Analysis and Correspondence Analysis were used to determine risk factors for ED referral. RESULTS: We recruited 49 post-ED patients and 126 outpatients. The main reasons for ED admission were poor response to acute treatment and aura-related symptoms. Headache diagnoses made in ED were generally not confirmed later (overall concordance of 47%), except for cluster headache (CH) and migraine with aura (MA). ED patients complained higher headache intensity, longer duration, and prolonged aura compared to outpatients. Aura was the main risk factor associated with ED admission on statistical models, while less prominent risk factors were sex, age, and years from migraine onset. CONCLUSIONS: ED patients presented a more severe headache clinical phenotype compared with outpatients. Headache diagnosis remains difficult in the emergency setting and is more easily achieved for the headache forms with standout features, such as MA or CH. According to statistical models, the aura is the most important risk factor for ED admissions.

Nummular Headache - a Case Report of a Rare Entity.

PURPOSE OF REVIEW: The purpose of this manuscript is to shed light on systematic work-up of a diagnostic challenge such as nummular headache (NH), and to summarize the relevant literature on NH. RECENT FINDINGS: The specific nature of the shape of the pain site is usually characteristic of NH. Multiple modalities of investigation including succinct imaging are necessary to successfully rule out other similar conditions. A 26-year-old female patient of Asian-Indian origin presented to the clinic with the chief complaint of chronic persistent left parietal headache for more than 10 years, which has been worsening over the past few days with no specific identifiable trigger. The diagnosis of nummular headache is challenging and confusing due to the rare occurrence and inadequate references in the literature. Appropriate imaging was done, which revealed no pathology that could explain the headache presentation. These findings are consistent with our diagnosis of nummular headache, and helped in the successful management of the case.

Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation.

BACKGROUND: While transcranial magnetic stimulation (TMS) has been studied for the treatment of psychiatric disorders, emerging evidence supports its use for pain and headache by stimulating either motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). However, its clinical implementation is hindered due to a lack of consensus in the quality of clinical evidence and treatment recommendation/guideline(s). Thus, working collaboratively, this multinational multidisciplinary expert panel aims to: 1) assess and rate the existing outcome evidence of TMS in various pain/headache conditions; 2) provide TMS treatment recommendation/guidelines for the evaluated conditions and comorbid depression; and 3) assess the cost-effectiveness and technical issues relevant to the long-term clinical implementation of TMS for pain and headache. METHODS: Seven task groups were formed under the guidance of a 5-member steering committee with four task groups assessing the utilization of TMS in the treatment of Neuropathic Pain (NP), Acute Pain, Primary Headache Disorders, and Posttraumatic Brain Injury related Headaches (PTBI-HA), and remaining three assessing the treatment for both pain and comorbid depression, and the cost-effectiveness and technological issues relevant to the treatment. RESULTS: The panel rated the overall level of evidence and recommendability for clinical implementation of TMS as: 1) high and extremely/strongly for both NP and PTBI-HA respectively; 2) moderate for postoperative pain and migraine prevention, and recommendable for migraine prevention. While the use of TMS for treating both pain and depression in one setting is clinically and financially sound, more studies are required to fully assess the long-term benefit of the treatment for the two highly comorbid conditions, especially with neuronavigation. CONCLUSIONS: After extensive literature review, the panel provided recommendations and treatment guidelines for TMS in managing neuropathic pain and headaches. In addition, the panel also recommended more outcome and cost-effectiveness studies to assess the feasibility of the long-term clinical implementation of the treatment.

TRP Channels in the Focus of Trigeminal Nociceptor Sensitization Contributing to Primary Headaches.

Pain in trigeminal areas is driven by nociceptive trigeminal afferents. Transduction molecules, among them the nonspecific cation channels transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), which are activated by endogenous and exogenous ligands, are expressed by a significant population of trigeminal nociceptors innervating meningeal tissues. Many of these nociceptors also contain vasoactive neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P. Release of neuropeptides and other functional properties are frequently examined using the cell bodies of trigeminal neurons as models of their sensory endings. Pathophysiological conditions cause phosphorylation, increased expression and trafficking of transient receptor potential (TRP) channels, neuropeptides and other mediators, which accelerate activation of nociceptive pathways. Since nociceptor activation may be a significant pathophysiological mechanism involved in both peripheral and central sensitization of the trigeminal nociceptive pathway, its contribution to the pathophysiology of primary headaches is more than likely. Metabolic disorders and medication-induced painful states are frequently associated with TRP receptor activation and may increase the risk for primary headaches.

Paroxysmal pressing headache: A new short-lasting headache.

INTRODUCTION: In this report we describe a series of patients with a previously undescribed headache. METHODS: Over a 4-year period, we recruited 14 patients with a distinctive type of head pain of unknown cause that did not meet diagnostic criteria for other primary headaches. RESULTS: Nine women and five men with a mean age of 49.6 years (standard deviation, 17.8) presented with spontaneous headache attacks lasting 2-15 minutes. In each attack, the pain was localized to a region of one side of the head. Pain location varied between episodes in 12 patients. Pain quality was pressing, and pain intensity was mild to severe. There were no accompanying symptoms. Physical examination and all ancillary tests were unremarkable. Among seven patients who tried pharmacological treatments, one responded to antidepressants, another to indomethacin and three to other nonsteroidal anti-inflammatory drugs or simple analgesics. CONCLUSIONS: Paroxysmal pressing headache may be a new headache syndrome marked by short duration of the pain and shifting location.

Brain structure and function related to headache: Brainstem structure and function in headache.

OBJECTIVE: To review and discuss the literature relevant to the role of brainstem structure and function in headache. BACKGROUND: Primary headache disorders, such as migraine and cluster headache, are considered disorders of the brain. As well as head-related pain, these headache disorders are also associated with other neurological symptoms, such as those related to sensory, homeostatic, autonomic, cognitive and affective processing that can all occur before, during or even after headache has ceased. Many imaging studies demonstrate activation in brainstem areas that appear specifically associated with headache disorders, especially migraine, which may be related to the mechanisms of many of these symptoms. This is further supported by preclinical studies, which demonstrate that modulation of specific brainstem nuclei alters sensory processing relevant to these symptoms, including headache, cranial autonomic responses and homeostatic mechanisms. REVIEW FOCUS: This review will specifically focus on the role of brainstem structures relevant to primary headaches, including medullary, pontine, and midbrain, and describe their functional role and how they relate to mechanisms of primary headaches, especially migraine.