Chronic Daily Headache Research Articles

Prevalence and profile of headache in school-going adolescents aged 10 – 19 years in Benin City: a cross sectional survey

IntroductionAdolescent headaches significantly impact their daily functioning, academic performance, and quality of life. The occurrence of headaches is influenced by genetics, psychological stressors, and environmental exposures. Understanding these influences is crucial for effective management strategies.AimTo determine the prevalence, characteristics, and associated factors of headaches among school-going adolescents in Benin City, Nigeria.MethodsThis was a descriptive cross-sectional study among secondary school students. Using a structured questionnaire, data on sociodemographics, headache characteristics, triggers, and impacts were collected. The chi-square test was used to assess the association between the presence of headaches and categorical covariates. All analyses used a significance level of p<0.05.ResultOf the 486 respondents 235 (48.4%) were boys and 251 (48.3%) were girls with a M:F ratio of 1:1.07. The mean age of the study participant was 13.7 (+ 1.78) years. The one-year prevalence of headache was 84%. 92 (18.9%) of those reporting headaches met the diagnostic criteria for chronic daily headache. The most common impact of headache was poor concentration (110; 22.6%). Psychological stress (55.3%) and poor sleep (26.1%) were the most commonly reported headache triggers.ConclusionMore than four in five school-going adolescents have headache at one time in the past year. Reading and concentration problems are the most common adverse effect of headache in adolescents.

Effectiveness and Tolerability of Anti-Calcitonin Gene-Related Peptide Therapy for Migraine and Other Chronic Headaches in Adolescents and Young Adults: A Retrospective Study in the USA.

This retrospective study assesses the efficacy and tolerability of anti-calcitonin gene-related peptide (anti-CGRP) therapy in adolescents and young adults (ages 12-21) with migraine and chronic daily headaches unresponsive to standard treatments. Migraines in this demographic significantly impair school performance, self-esteem, psychological well-being, and cognitive health. These young patients are also particularly sensitive to the side effects of conventional medications, which are often prescribed off-label and come with high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels observed during migraines suggest that anti-CGRP therapies, successful in adult populations, may also benefit this younger age group. Over a three-year period, patients at a specialized pediatric headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, and galcanezumab) and small-molecule CGRP receptor antagonists (ubrogepant, rimegepant, and atogepant), administered either alone or in combination with OnabotulinumtoxinA. Data were extracted from the hospital's electronic medical records, and patient progress was consistently documented using a structured template for each clinic visit. Additional patient satisfaction data were collected via telephone follow-ups and patient message reviews. The study included 23 patients, primarily treated for chronic migraine (CM) (78.3%), with a smaller subset addressing episodic migraine (EM), new daily persistent headaches (NDPHs), and post-traumatic headaches (PTHs). Comprehensive demographic and clinical data, including age, treatment duration, history of preventive treatment failures, and comorbidities like psychiatric conditions and sleep disorders, were collected. Anti-CGRP therapies, particularly when combined with traditional treatments or OnabotulinumtoxinA, resulted in significant improvements: 91.3% of patients experienced reduced migraine duration and intensity, 82.6% reported improvements in other bothersome symptoms, and 73.9% saw an improved response to rescue medications. Additionally, 78.3% of patients reported a reduction in their use of rescue medications per week by more than 50%, and emergency room visits were reduced for 56.5% of patients. Significant reductions in headache days were observed in 82.6% of patients after one month and 87% after three months, with nearly 40% experiencing more than a 50% reduction in both periods. The greatest benefits were observed in patients treated for more than six months. Adverse effects were minimal, with 95.7% of patients reporting no side effects, and patient satisfaction was high, with 69.6% opting to continue treatment. Overall, this study highlights the substantial potential of anti-CGRP therapy in improving outcomes for adolescents and young adults with CM and EM, offering a promising approach for a demographic that faces considerable challenges with conventional treatment options. However, further research is needed to confirm these findings and expand clinical applications in this age group.

Persistent headache and chronic daily headache after COVID-19: a prospective cohort study.

Little is known about the frequency and impact of the persistent headache and about the incidence of chronic daily headache (CDH) after coronavirus disease 2019 (COVID-19). The aim of this prospective cohort study was to assess the incidence, risk factors, characteristics, and impact of CDH in patients with COVID-19. In the first stage, 288 patients were interviewed by telephone after the acute phase of COVID-19. Subsequently, 199 patients who presented headache were reinterviewed at least one year after COVID-19. Headaches that persisted beyond the acute phase of COVID-19 for three or more months and presented frequency ≥ 45 days over the first three months were considered to be CDH. One hundred and twenty-three patients were included, 56% were females; median age: 50 years (25th and 75th percentile: 41;58). The headache persisted beyond the acute phase of COVID-19 in 52%, and 20.3% had CDH (95% confidence interval: 13.6-28.2). Individuals who previously had headaches and who had headaches of greater intensity during the acute phase were at higher risk of developing CDH. The group with CDH included more females, greater impact of headache, more persistence of headache beyond the 120th day of COVID-19 and less throbbing headache than did the other individuals whose headache persisted. Patients who had COVID-19 had a high incidence of CDH. Previous headache and greater intensity of headache were associated with higher risk of CDH.

Therapeutic Patient Education as Part of the Physiotherapy Management of Adults with Headache: A Scoping Review.

Physiotherapy interventions for headache mostly include exercise and manual therapy. Yet, the complex nature of headache, sometimes characterized by symptoms of facilitated central pain mechanisms, demands an individualized approach in which therapeutic patient education could be supportive. This scoping review aimed to summarize the position of therapeutic patient education within the physiotherapy management of adults with headache. PubMed, EMBASE, Web of Science, and Scopus were searched. The search-query comprised terminology relating to "headache", "education", and "physiotherapy". Eligibility criteria were: adults with headache, interventions including education within the domain of physiotherapy, reviews, clinical trials, cohort, case report, case-control studies. Eleven publications were included from the 281 retrieved publications. These publications were clinical trials (n = 4), reviews (n = 4), case-reports (n = 2), and a guideline (n = 1). Type of headaches studied were migraine (n = 3), post-traumatic headache (n = 2), tension-type headache (n = 2), cervicogenic headache (n = 1), primary headaches (n = 1), chronic daily headache (n = 1), and mixed migraine-cervicogenic headache (n = 1). Education seems an umbrella-term for postural education, lifestyle advice, and pain education. Three themes emerged across the publications: handling headache triggers (migraine, post-traumatic headache), promoting active lifestyle (post-traumatic headache, chronic daily headache, migraine), evaluating posture (post-traumatic headache, chronic daily headache, tension-type headache, cervicogenic headache). All publications recommended education in the management of headache. Only one (of the 11 included) publication described the educational program and determined its efficacy. Based on this scoping review, therapeutic patient education seems supported within physiotherapy management of headache. However, it is unclear how such education is tailored to the specific needs of the individual, the headache subtype, or when it should be added to physiotherapy management of headache.

FACTORS ASSOCIATED WITH DEVELOPING CHRONIC DAILY HEADACHE IN MIGRAINE PATIENTS

To examine the factors associated with developing chronic daily headache in migraine patients. Two hundred patients with migraine were selected for this descriptive study conducted from 01-Sept-2023 to 30-Nov-2023 at the Department of Medicine, Lady Reading Hospital, Medical Teaching Institution, Peshawar. Factors associated with developing chronic daily headache were assessed. SPSS 23 was employed for analyzing the data. The mean age was 38.09±12.03 years. The frequency of chronic daily headache in our study was 31 (15.5%). Female gender (p = 0.02), smoking (p = 0.0001), high caffeine intake (p = 0.0001), painkiller overuse (p = 0.0001) and obesity (p = 0.0001) were factors significantly identified for developing chronic daily headache. We conclude that the factors for developing chronic daily headache in migraine patients were female gender, smoking, high intake of pain relieving medicines, high intake of caffeinated drinks and obesity.

Normative body mass-adjusted reference ranges of magnetic resonance imaging signs commonly used in diagnosing idiopathic intracranial hypertension in a healthy standard population

Patients with chronic daily headaches (CDH) are often a diagnostic challenge and frequently undergo neuroimaging. One common underlying cause of CDH is idiopathic intracranial hypertension (IIH). However, certain neuroimaging abnormalities that suggest IIH, such as optic nerve sheath diameters (ONSD), pituitary gland height, and venous sinus diameter, require interpretation due to the absence of established normative values. Notably, intracranial pressure is known to varies with age, sex and weight, further complicating the determination of objectively abnormal findings within a specific patient group. This study aims to assist clinical neuroradiologists in differentiating neuroimaging results in CDH by providing weight-adjusted normative values for imaging characteristics of IIH. In addition to age and BMI we here assessed 1924 population-based T1-weighted MRI datasets of healthy participants for relevant MRI aspects of IIH. Association to BMI was analyzed using linear/logistic regression controlled for age and stratified for sex. ONSD was 4.3 mm [2.8; 5.9]/4.6 mm [3.6; 5.7] and diameter of transverse sinus was 4.67 mm [1.6; 6.5]/4.45 mm [3.0; 7.9]. Height of pituitary gland was 5.1 mm [2.2;8.1]/4.6 mm [1.9;7.1] for female and male respectively. Values generally varied with BMI with regression slopes spanning 0.0001 to 0.05 and were therefor presented as normative values stratified by BMI. Protrusion of ocular papilla, empty sella and transverse sinus occlusion were rare in total. Our data show an association between BMI and commonly used MRI features for diagnosing IIH. We provide categorized normative BMI values for ONSD, pituitary gland height, and transverse sinus diameter. This distinction helps objectively identify potential IIH indicators compared to regular population norms, enhancing diagnostic accuracy for suspected IIH patients. Notably, optic nerve head protrusion, empty sella, and transverse sinus occlusion are rare in healthy individuals, solidifying their importance as imaging markers regardless of BMI.

Hybrid Peripheral Neurostimulation to Treat Chronic Post-Meningitis Headache- A Case Report

Introduction: Chronic post-meningitis headaches present clinically with persistent symptoms often mirroring migraines or tension-type headaches. These frequently include photophobia, phonophobia, and associated nausea and vomiting, similar to other primary headache disorders. Central to the pathology of viral meningitis is the inflammation of the meninges—the intricate protective sheaths encasing the brain and spinal cord. Case: This case study details a 56-year-old female patient experiencing chronic daily headaches and facial pain following an episode of self-resolving viral meningitis. Traditional therapeutic interventions failed to achieve satisfactory symptom control for the patient. In response to the treatment-resistant nature of the patient’s condition, a neurostimulator strategy was implemented providing over 95% symptom relief reported at week 12 post-implantation. This strategy employed a hybrid approach combining high cervical and occipital lead placements, with the goal of enhancing neurostimulator coverage and mitigating the patient’s persistent symptoms. Conclusion: Preliminary observations suggest a potential avenue for further research and exploration in the domain of refractory headaches. Hybrid peripheral neurostimulation, as an emerging paradigm in neuromodulation, draws from the principles of neural plasticity and targeted neuromodulation. This case serves as an exemplar for refractory post-meningitis headaches, offering an innovative solution when traditional therapies have failed to provide relief

Utility of Repetitive Transcranial Magnetic Stimulation for Chronic Daily Headache Prophylaxis: A Systematic Review and Meta-Analysis.

Management of chronic daily headaches (CDH) remains challenging due to the limited efficacy of standard prophylactic pharmacological measures. Several studies have reported that repetitive transcranial magnetic stimulation (rTMS) can effectively treat chronic headaches. The objective was to determine the utility of rTMS for immediate post-treatment and sustained CDH prophylaxis. All procedures were conducted per PRISMA guidelines. PubMed, Scopus, Web of Science, and ProQuest databases were searched for controlled clinical trials that have tested the efficacy of rTMS on populations with CDH. DerSimonian-Laird random-effects meta-analyses were performed using the 'meta' package in R to examine the post- vs. pre-rTMS changes in standardized headache intensity and frequency compared to sham-control conditions. Thirteen trials were included with a combined study population of N = 538 patients with CDH (rTMS, N = 284; Sham, N = 254). Patients exposed to rTMS had significantly reduced standardized CDH intensity and frequency in the immediate post-treatment period (Hedges' g = -1.16 [-1.89, -0.43], p = 0.002 and Δ = -5.07 [-10.05, -0.11], p = 0.045 respectively). However, these effects were sustained marginally in the follow-up period (Hedges' g = -0.43 [-0.76, -0.09], p = 0.012 and Δ = -3.33 [-5.52, -1.14], p = 0.003). Significant between-study heterogeneity was observed, at least partially driven by variations in rTMS protocols. Despite the observed clinically meaningful and statistically significant benefits in the immediate post-treatment period, the prophylactic effects of rTMS on CDH do not seem to sustain with discontinuation. Thus, the cost-effectiveness of the routine use of rTMS for CDH prophylaxis remains questionable. Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42021250100).

The Use of Botulinum Toxin Type A in Medically Refractory Pediatric Patients With Chronic Daily Headaches and Its Impact on the Quality of Life.

Background: Chronic migraine in children has been a challenging condition to treat, prompting the investigation of alternative therapies. This retrospective single-center chart review aimed to evaluate the efficacy and safety of Botox injections for managing chronic migraine in children. Methods: The study included children with chronic daily headaches and chronic migraine who were medically refractory to previous treatments at OSF Healthcare/Illinois Neurological Institute, Peoria, between 2015 and 2021. Botox injections were administered quarterly following a specific protocol. Data were obtained from electronic medical records by manual review. Results: Twenty-four patients met the inclusion criteria (median age 15.4 years, 87% female). Comorbidities included depression (41.6%) and sleep disturbances (33.2%). Prior to Botox treatment, patients had been tried on a median number of 5 (interquartile range [IQR] 4, 7) medications. Botox injections resulted in a significant reduction in headache frequency, with a mean difference (6 months vs pretreatment) in the Headache Impact Test (HIT 3) scores of -19.6 (95% CI -24.8, -14.3), P < .001, and mean difference in the Migraine Disability Assessment (MIDAS) scores of -50.8 (95% CI -62.6, -39.0, P < .001). Subjective improvements included mood enhancement (13/24, 54.2%) and improved concentration (12/24, 50%). Treatment-related side effects were reported by 5/24 (20%) of patients and were mostly mild to moderate. Conclusions: Botox injections offer a promising therapeutic option for managing chronic migraine in children who have not responded to traditional medications. Future controlled trials and long-term follow-up studies are needed to further evaluate Botox treatment's benefits and adverse effects in children with chronic migraine.

Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study

Introduction: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. Methods: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. Results: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04–3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03–1.24), less than high school (OR, 1.08; 95%, 1.01–1.15), without depression (OR, 1.06; 95%, 1.01–1.12), and without anxiety (OR, 1.06; 95%, 1.01–1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. Conclusion: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Association Between Iron Deficiency Anemia and Chronic Daily Headache

Background: Chronic daily headache (CDH) and iron deficiency anemia (IDA) are prevalent health issues with significant impact on individuals' quality of life. Understanding the relationship between these conditions is essential for developing effective treatment strategies. Objective: This study aims to investigate the association between iron deficiency anemia and chronic daily headache. Methods: A case-control study was conducted at Pak Emirates Military Hospital, Rawalpindi, Pakistan, from February to July 2023. The study included 140 patients diagnosed with CDH and 140 age- and sex-matched controls without a history of CDH. Demographic data (age, gender, location, education, marital status) were collected along with clinical characteristics (headache frequency, intensity, duration) and hematological parameters (hemoglobin level, serum ferritin level, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, hematocrit level, mean corpuscular hemoglobin concentration). Statistical analysis was performed using chi-square tests and ANOVA. Results: There were no significant differences in demographic characteristics between the CDH and control groups. CDH patients exhibited higher headache frequency (57.14% experienced headaches 10-15 times per month), intensity (64.43% reported NRS score of 5-8), and duration (87.15% reported headache duration of over 4 hours) compared to controls. Hematological analysis revealed significantly lower mean hemoglobin (9.85±2.13 g/dL) and serum ferritin levels (30.72±7.65 ng/mL) in CDH patients compared to controls (13.1±2.70 g/dL and 65.09±12.82 ng/mL, respectively). A significant association between IDA and CDH was established (p&lt;0.05). Conclusion: The study demonstrates a significant association between iron deficiency anemia and chronic daily headache, highlighting the potential role of iron deficiency in the development of CDH.

Phenotype of new daily persistent headache: subtypes and comparison to transformed chronic daily headache

BackgroundIt is unknown whether new daily persistent headache (NDPH) is a single disorder or heterogenous group of disorders, and whether it is a unique disorder from chronic migraine and chronic tension-type headache. We describe a large group of patients with primary NDPH, compare its phenotype to transformed chronic daily headache (T-CDH), and use cluster analysis to reveal potential sub-phenotypes in the NDPH group.MethodsWe performed a case–control study using prospectively collected clinical data in patients with primary NDPH and T-CDH (encompassing chronic migraine and chronic tension-type headache). We used logistic regression with propensity score matching to compare demographics, phenotype, comorbidities, and treatment responses between NDPH and T-CDH. We used K-means cluster analysis with Gower distance to identify sub-clusters in the NDPH group based on a combination of demographics, phenotype, and comorbidities.ResultsWe identified 366 patients with NDPH and 696 with T-CDH who met inclusion criteria. Patients with NDPH were less likely to be female (62.6% vs. 73.3%, p < 0.001). Nausea, vomiting, photophobia, phonophobia, motion sensitivity, vertigo, and cranial autonomic symptoms were all significantly less frequent in NDPH than T-CDH (p value for all < 0.001). Acute treatments appeared less effective in NDPH than T-CDH, and medication overuse was less common (16% vs. 42%, p < 0.001). Response to most classes of oral preventive treatments was poor in both groups. The most effective treatment in NDPH was doselupin in 45.7% patients (95% CI 34.8–56.5%). Cluster analysis identified three subgroups of NDPH. Cluster 1 was older, had a high proportion of male patients, and less severe headaches. Cluster 2 was predominantly female, had severe headaches, and few associated symptoms. Cluster 3 was predominantly female with a high prevalence of migrainous symptoms and headache triggers.ConclusionsWhilst there is overlap in the phenotype of NDPH and T-CDH, the differences in migrainous, cranial autonomic symptoms, and vulnerability to medication overuse suggest that they are not the same disorder. NDPH may be fractionated into three sub-phenotypes, which require further investigation.

The insufficiency of a simple stress question in assessing stress for chronic daily headache in clinical practice

BackgroundIn managing chronic daily headaches (CDH), a comprehensive approach is necessary to evaluate stress, a closely linked factor. However, limited time and costs often lead to the use of a simple stress question in clinical settings. This study aims to assess the validity of using a simple stress question for CDH patients and explore its implications for clinical practice. MethodsWe recruited 103 patients with CDH who completed structured self-administered questionnaires, including a simple stress question ("Have you had any stress or concerns in the last 4 weeks?") and validated Korean versions of questionnaires for depression, anxiety, insomnia, and the Brief Encounter Psychosocial Instrument (BEPSI). A headache specialist conducted clinical interviews. The stress group consisted of patients who acknowledged overt stress (answering "yes" to the simple question) and covert stress (initially answering "no" but later admitting during the interview). Results showed no statistical difference between the subgroups, so they were combined as the "acknowledged stress" group. ResultsOut of 103 patients, 54.4% had chronic migraine, 45.6% had chronic tension-type headache, and 66 patients (64.1%) acknowledged experiencing stress. No significant differences were found in demographic and clinical characteristics, BEPSI stress assessment, or depression, anxiety, and insomnia profiles between patients with overt stress (n = 51) and covert stress (n = 15). The average BEPSI score was 2.3 ± 0.9, with 45.6% of patients exceeding the criteria (>2.4). Two (5.4%) patients in denial of stress had scores above the BEPSI criteria. Among patients below the criteria of BEPSI, 21 acknowledged stress, while 35 denied stress, with no significant differences observed. ConclusionsThis study suggests the limitations of relying solely on a simple stress question for assessing stress in patients with CDH in clinical practice. It is possible to encounter covert stress, include individuals who do not exhibit noticeable stress, and misclassify stress levels. To overcome these limitations, it is necessary to foster a supportive environment for open communication on stress and implement a comprehensive assessment strategy when needed.

Cefalea crónica tipo tensión: una nueva experiencia de tratamiento

Introducción: la cefalea tipo tensión es la forma más común de dolor de cabeza y su forma crónica una de las más difíciles de tratar, causa gran discapacidad a pacientes y representa enormes costos socioeconómicos, está relacionada con factores de tensión emocional y muscular. Las propuestas terapéuticas con las que se cuenta incluyen AINE, fisioterapia, infiltraciones con toxina botulínica en músculos pericraneales.&#x0D; Objetivo: evaluar la efectividad en el tratamiento de la cefalea crónica tipo tensión con infiltración intramuscular con betametasona, un esteroide de depósito más lidocaína al 1%, en puntos de tensión muscular a niveles suboccipital, paraespinales cervicales y trapecio, acompañados de fisioterapia y un proceso educativo a pacientes y familiares.&#x0D; Materiales y métodos: estudio retrospectivo, en el que se midió la efectividad del tratamiento utilizando la escala visual análoga (EVA). Los datos fueron analizados en el programa SPSS por medio de porcentajes, frecuencias y proporciones.&#x0D; Resultados: de un total de 138 casos de cefalea crónica diaria tipo tensión, con edad promedio 51 años, 76,8% sexo femenino, 21% se asocia a trastorno ansioso; 8,7% a sensación vertiginosa y 8,7% síntomas depresivos; 8% insomnio; 78,2% de los pacientes refirieron mejoría con el tratamiento propuesto y de estos, 85,5% de los casos se cuantificaron según la EVA, 66,8% presentaron mejoría entre 7 y 10 puntos; el mayor porcentaje estuvo asintomático durante tres meses, 22,5% libres de crisis durante el seguimiento total de siete meses y 58,7% reincidieron.&#x0D; Conclusión: se evidencia que la combinación de infiltraciones intramusculares con betametasona más lidocaína y fisioterapia y un proceso de educación del personal médico a pacientes y familiares es un tratamiento eficaz, sin efectos adversos, en el manejo de la cefalea crónica tipo tensión, considerada una de las más difíciles de tratar.

Associations between Plasma Lipid Mediators and Chronic Daily Headache Outcomes in Patients Randomized to a Low Linoleic Acid Diet with or without Added Omega-3 Fatty Acids.

A previous report showed that 12-week lowering of dietary omega-6 linoleic acid (LA) coupled with increased omega-3 polyunsaturated fatty acid (PUFA) intake (H3-L6 diet) reduced headache frequency and improved quality of life in patients with chronic daily headaches (CDHs) compared to dietary LA reduction alone (L6 diet). The trial also showed that targeted dietary manipulation alters PUFA-derived lipid mediators and endocannabinoids. However, several additional classes of lipid mediators associated with pain in preclinical models were not measured. The current secondary analysis investigated whether the clinical benefits of the H3-L6 diet were related to changes in plasma unesterified PUFA-derived lipid mediators known to be involved in nociception, including prostanoids. Lipid mediators were measured by ultra-high-pressure liquid chromatography coupled with tandem mass-spectrometry. Compared to baseline, dietary LA lowering with or without added omega-3 fatty acids did not alter unesterified n-6 PUFA-derived lipid mediators, although several species derived from LA, di-homo-gamma-linolenic acid, and arachidonic acid were positively associated with headache frequency and intensity, as well as mental health burden. Alpha-linolenic acid (ALA)-derived metabolites were also associated with increased headache frequency and intensity, although they did not change from the baseline in either dietary group. Compared to baseline, docosahexaenoic acid (DHA)-derived epoxides were more elevated in the H3-L6 group compared to the L6 group. Diet-induced elevations in plasma DHA-epoxides were associated with reduced headache frequency, better physical and mental health, and improved quality of life (p < 0.05). Prostanoids were not detected, except for PGF2-alpha, which was not associated with any outcomes. This study demonstrates that diet-induced changes in DHA-epoxides were associated with pain reduction in patients with chronic headaches, whereas n-6 PUFA and ALA metabolites were associated with nociception. Lipid mediator associations with mental health and quality of life paralleled pain management outcomes in this population. The findings point to a network of multiple diet-modifiable lipid mediator targets for pain management in individuals with CDHs.

The Effectivity of Anodal tDCS Over Somatosensory Cortex in Reducing Central Pain Sensitization in Chronic Daily Headache

The Effectivity of Anodal tDCS Over Somatosensory Cortex in Reducing Central Pain Sensitization in Chronic Daily Headache

Trial protocol for a multicenter randomized controlled trial to assess the efficacy and safety of intravenous ketamine for chronic daily headaches: the “KetHead” trial

BackgroundChronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to conventional medical management and/or patients cannot afford expensive treatments. It is stipulated that CDH share a mechanism of central sensitization in the trigeminocervical complex, mediated by activation of the N-methyl-d-aspartate (NMDA) receptors. Ketamine, a non-competitive NMDA antagonist, has been used in the treatment of chronic pain, but its role in CDH has not been completely established. This trial aims to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion.MethodsA multicenter, placebo-controlled, randomized controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessors. The study will include 56 adults with a CDH diagnosis as per ICHD-3 criteria. Participants will be randomized (1:1) to either ketamine (1 mg. kg−1 bolus followed by infusion of 1 mg. kg−1. h−1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h. The impact on the number of monthly headache days, headache intensity, physical activity, mood, sleep, quality of life, analgesic consumption, and adverse effects will be recorded at baseline, immediately post-infusion, and from 1 to 28 days, 29 to 56 days, and 57 to 84 days after the infusionDiscussionDespite advancements in treatment, many patients continue to suffer from CDH. This trial investigates whether high-dose IV ketamine infusions can effectively and safely improve the CDH burden as compared to a placebo infusion. This treatment could become a safe, affordable, and widely available option for patients living with refractory headache.Trial registrationClinicalTrials.gov NCT05306899. Registered on April 1, 2022

Association between iron deficiency anemia and chronic daily headache: A case-control study

We aimed to determine the association between iron deficiency anemia and chronic daily headache. This case-control study was conducted in a tertiary care center in Dehradun, India. One hundred patients with chronic daily headache were randomly selected for the study with an equal number of controls. Subsets of chronic daily headache were diagnosed as per the 3rd edition of the International Classification of Headache Disorders. The study participants were assessed for iron deficiency anemia. The mean age of the patients was 51.1 ± 22.1 years. Male: female ratio was 1:1.08. Chronic migraine was present in 62 (62%), tension-type headache in 23 (23%), and new daily persistent headache in 15 (15%) patients. The majority (96%) of patients had chronic daily headache of mild to moderate severity. Chronic daily headache was of long duration in all patients. Sixty-four (64%) patients had anemia of which 51 (51%) patients had iron deficiency anemia. Iron deficiency anemia showed a significant association with chronic daily headache (p < 0.001), but not with its type, subtype, and duration. Severe iron deficiency anemia had a significant association with the severity of chronic daily headache (p = 0.021). Serum iron, ferritin, total iron-binding capacity, and transferrin saturation also had a significant association with chronic daily headache (p < 0.05 for each), but not with its type, subtype, duration, and severity. Logistic regression analysis showed that iron deficiency anemia, total iron-binding capacity, and transferrin saturation had an independent association with chronic daily headache (p < 0.05 for each). Iron deficiency anemia had an independent association with chronic daily headache. Severe iron deficiency anemia was related to the severity of chronic daily headache.

PACAP-PAC1 receptor inhibition is effective in opioid induced hyperalgesia and medication overuse headache models

Opioids prescribed for pain and migraine can produce opioid-induced hyperalgesia (OIH) or medication overuse headache (MOH). We previously demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) is upregulated in OIH and chronic migraine models. Here we determined if PACAP acts as a bridge between opioids and pain chronification. We tested PACAP-PAC1 receptor inhibition in novel models of opioid-exacerbated trigeminovascular pain. The PAC1 antagonist, M65, reversed chronic allodynia in a model which combines morphine with the migraine trigger, nitroglycerin. Chronic opioids also exacerbated cortical spreading depression, a correlate of migraine aura; and M65 inhibited this augmentation. In situ hybridization showed MOR and PACAP co-expression in trigeminal ganglia, and near complete overlap between MOR and PAC1 in the trigeminal nucleus caudalis and periaqueductal gray. PACAPergic mechanisms appear to facilitate the transition to chronic headache following opioid use, and strategies targeting this system may be particularly beneficial for OIH and MOH.

The Efficacy of Repetitive Transcranial Magnetic Stimulation in Treating Patients with Chronic Daily Headache

The Efficacy of Repetitive Transcranial Magnetic Stimulation in Treating Patients with Chronic Daily Headache