Headache最新文献

Objective: This study aimed to provide proof-of-concept that multi-receptor antagonist peptides can be generated by covalently linking independent antagonist peptides that block calcitonin gene-related peptide (CGRP_8-37) or pituitary adenylate cyclase-activating peptide (PACAP)/vasoactive intestinal peptide (VIP) (PACAP_6-38) activity.

Background: The neuropeptides CGRP and PACAP are implicated in migraine and pain pathogenesis. CGRP and PACAP are elevated during a migraine attack, and following infusion of either peptide, patients develop migraine-like attacks. This indicates that targeting both these systems may provide therapeutic benefits. Mechanistic studies suggest that these peptides largely act independently from one another. Therefore, blocking the activity of both CGRP and PACAP simultaneously could provide a clinical advantage over individual blockade. One strategy is to develop a single antagonist capable of inhibiting the signaling of both CGRP and PACAP receptors, a multi-receptor antagonist. N-terminal truncation of CGRP and PACAP generates the antagonists CGRP_8-37 and PACAP_6-38, respectively. These are commonly used as research tools for the CGRP and PACAP receptors. These peptide antagonists were, therefore, used as the basis for the design of multi-receptor antagonists against the CGRP and PACAP receptors and to test their functionality in vitro.

Methods: To generate multi-receptor antagonists, CGRP_8-37 was linked through 1,3-dipolar cycloaddition using click chemistry to PACAP_6-38 at amino acid residues 21, 34, or 38. The ability of these multi-receptor antagonists to block CGRP activity (CGRP and AMY₁ receptors) and PACAP-38, PACAP-27, and VIP activity (PAC₁, VPAC₁, and VPAC₂ receptors) was then characterized in transfected Cos7 cells. The peptides were then further examined in pain-relevant rat spinal cord cultures, as a model of endogenous receptors.

Results: Multi-receptor antagonists were successfully generated, displaying similar antagonist potency to their parental antagonists in both transfected Cos7 cells and in spinal cord cultures. Interestingly, CGRP_8-37 linked to position 38 of PACAP_6-38 was a more potent antagonist of CGRP activity than CGRP_8-37.

Conclusion: This study provides proof-of-concept evidence for the development of potent multi-receptor antagonists capable of blocking both CGRP and PACAP activity.

Background: Treprostinil, a prostacyclin analog, remedies pulmonary arterial hypertension through vasodilation of both pulmonary and systemic arterial vascular beds. Headache is a known side effect of treprostinil and prostacyclin analogs in general, but the mechanism by which they cause headache is unknown. Current recommendations for treatment of severe headaches from prostacyclin analogs include only one drug class, opioids. Acetazolamide is a carbonic anhydrase inhibitor that lowers intracranial pressure by reducing the production of cerebrospinal fluid.

Case: A 44-year-old female inpatient developed a continuous headache, much worse supine than standing, shortly after starting treprostinil for pulmonary artery hypertension. Imaging studies showed no explanatory anatomical process. Her comorbidities precluded the use of triptans, ergots, and non-steroidal anti-inflammatory drugs, but her headache resolved rapidly with acetazolamide 250 mg twice daily. Acetazolamide and furosemide were stopped due to hypokalemia and vomiting, whereupon her headaches returned. Acetazolamide but not furosemide was then restarted, again with resolution of her headaches despite cessation of oxycodone.

Discussion/conclusion: This sequence suggests that treprostinil may cause headache by elevating intracranial pressure (ICP), possibly through cerebral vasodilation. We suspect that acetazolamide may have reduced her ICP enough to resolve her headache. To our knowledge, this report is the first description of both the possible underlying mechanism of action whereby prostacyclin analogs may cause headache, as well as treatment of the underlying cause of the headache rather than the symptom.

Objectives: To explore the available evidence on the role of antithrombotics as migraine preventive medication.

Background: In clinical practice, the use of antithrombotic drugs in individuals with migraine is sometimes considered, especially in the case of frequent auras, association with patent foramen ovale, or prothrombotic states. This paper systematically reviews evidence on antithrombotic agents' efficacy for migraine prevention.

Methods: We performed a systematic literature search on PubMed and Scopus including observational and interventional studies focused on antiplatelets or anticoagulants as preventive treatments for migraine. The search included studies published until June 30th, 2024. Ongoing trials on Clinicaltrials.org were also explored. Quality assessment used the Cochrane Risk of Bias 2 (RoB-2) tool for randomized controlled trials (RCTs) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) for observational studies. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO identifier CRD42024501531).

Results: Out of 1854 records, we found 12 RCTs and 8 observational studies investigating the impact of antithrombotic drugs in migraine prevention. Due to heterogeneity of data, a meta-analysis was not feasible. RCTs tested acetylsalicylic acid (ASA) alone (seven), ASA in combination with other preventive treatments (two), clopidogrel (one), dual antiplatelet treatment (one), and vitamin K antagonists (one). Observational studies tested ASA (three), vitamin K antagonists (three), and clopidogrel (two). No clear evidence of efficacy was found for the overall population of individuals with migraine. Limited evidence from old RCTs-not specifically addressing the role of antithrombotic drugs for migraine prevention-and observational studies showed a potential improvement of migraine with the use of antiplatelet agents, mostly ASA, in special populations, including males, individuals with migraine with aura, and those with patent foramen ovale.

Conclusions: Evidence supporting the effectiveness of antithrombotic drugs as a preventive treatment for patients with migraine is insufficient. As preliminary data show potential improvements in special populations in whom those agents act indirectly by ameliorating vascular function, RCTs are worth conducting.

Objectives/background: This study was undertaken to assess the prevalence of primary stabbing headache (PSH) among adult patients seeking medical attention for headache in a clinic-based setting. PSH is a primary headache disorder and is one of the representatives of indomethacin-responsive cephalalgias. The epidemiology of PSH in adult patients assessed for headache in a tertiary care setting remains not well established.

Methods: PubMed, Embase, MEDLINE, and ScienceDirect databases were thoroughly searched for observational studies published between January 1, 1988, and August 9, 2024, that reported the relative frequency of PSH among adult patients evaluated for headache in a clinic-based setting. The Meta-Analysis of Observational Studies in Epidemiology guidelines were strictly followed by the study's design. Risk of bias was assessed using the Joanna Briggs Institute Checklist for Studies Reporting Prevalence Data. The study's protocol was preregistered on PROSPERO (ID: CRD42024573776).

Results: Of the initial 1153 records, 15 articles (n = 35,904 individuals) met all of the eligibility criteria. Most of the studies revealed a low risk of bias. The prevalence of PSH among adult patients evaluated for headache in a tertiary care setting was 1.6% (95% confidence interval [CI] = 0.7-3.4, 95% prediction interval [PI] = 0.00-0.29), with substantial heterogeneity (I² = 98.42) noted across the studies. PSH was diagnosed more often in females than in males (1.6%, 95% CI = 0.8-3.2, 95% PI = 0.00-0.18 vs. 0.5%, 95% CI = 0.2-1.1, 95% PI = 0.00-0.06). The mean age at onset of PSH was 41.6 years (SD = 13.7), and the mean delay time of diagnosis was 64.6 months (SD = 73.9).

Conclusion: Our results showed that PSH is a rare headache disorder among adults evaluated for headache in a clinic-based setting. Moreover, PSH is typically diagnosed in the early fourth decade of life and predominantly in females.

Objective: To compare the risk of ischemic stroke in patients with migraine treated with first-line medications, including valproate, topiramate, metoprolol, timolol, or propranolol, versus those not receiving these treatments, using data from two large electronic health records datasets.

Background: The impact of first-line migraine medications on ischemic stroke risk in patients with migraine remains uncertain, highlighting the need for further investigation.

Methods: We conducted a retrospective case-control study using data from Vanderbilt University Medical Center (VUMC) and the All of Us Research Program. Cases were patients with a primary ischemic stroke diagnosis after their first migraine diagnosis, while controls had no ischemic stroke following their initial migraine diagnosis.

Results: In the VUMC database, 356 cases and 15,231 controls were identified; the All of Us database included 256 cases and 6590 controls. Propranolol was the only medication significantly associated with a reduced risk of ischemic stroke in female patients with migraine (VUMC: adjusted odds ratio [aOR] 0.55, 95% confidence interval [CI] 0.33-0.86, p = 0.013; All of Us: aOR 0.41, 95% CI 0.19-0.77, p = 0.010), particularly in those with migraine without aura (VUMC: aOR 0.53, 95% CI 0.29-0.90, p = 0.027; All of Us: aOR 0.28, 95% CI 0.10-0.62, p = 0.006). The Cox model showed lower ischemic stroke rates in propranolol-treated female patients with migraine at 10 years in the VUMC data (adjusted hazard ratio [aHR] 0.45, 95% CI 0.24-0.83; p = 0.011, log-rank p < 0.001) and 10 years in the All of Us data (aHR 0.29, 95% CI 0.09-0.87; p = 0.048, log-rank p = 0.003).

Conclusions: Among various migraine treatments, propranolol was notably associated with a significant reduction in ischemic stroke risk among female patients with migraine, particularly those without aura. These findings suggest a potential dual benefit of propranolol in managing migraine and reducing stroke risk, highlighting the need for further prospective studies to confirm these results and potentially inform clinical practice.

Objective: To determine the association between obstructive sleep apnea (OSA) and the incidence of migraine using a large population-based dataset, as well as to identify the at-risk target groups.

Background: Epidemiological and biochemical studies have provided evidence for the close connection between sleep disorders and migraine. Understanding the connections between OSA and migraine, as well as their shared risk factors, may provide new perspectives on the pathophysiology of both OSA and migraine and novel approaches to managing and treating these conditions.

Methods: This retrospective cohort study used data from the TriNetX network from 2010 to 2021. We compared 196,864 adult participants with OSA to a group of 196,864 participants who had never been diagnosed with OSA (1:1 propensity score-matching for age, sex, race, comorbidities, and body mass index [BMI] categories) in relation to the risk of incident migraine. We performed subgroup analyses based on age (18-39, 40-59, ≥60 years), sex (female, male), race (White, Black or African American, Asian), BMI categories (<18.5, 18.5-24.9, 25-29.9, ≥30 kg/m²), and the presence of hypoxemia (yes, no). Sensitivity analyses were performed to validate our findings.

Results: During the follow-up period, 12,613 (6.4%) and 6356 participants (3.2%) developed migraine in the OSA and non-OSA cohorts, respectively. Patients with OSA were found to have a 1.85-fold risk (hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.79-1.90) of incident migraine when compared to those without OSA, after accounting for age, sex, race, and baseline comorbidities. The results were consistent in sensitivity analyses (test-negative design: HR 1.39, 95% CI 1.28-1.49) and also cross-validated in a different dataset from TriNetX (Global Collaborative Research Network: HR 1.88, 95% CI 1.82-1.93). The results of subgroup analysis by sex, age, race, BMI categories, and the presence of hypoxemia were generally consistent.

Conclusion: We found OSA to be associated with an elevated risk of developing migraine using a large United States nationwide database, and the association was generalizable across sex, age, race, and BMI categories. Our results suggest that awareness of migraine should be increased among patients with OSA. The findings also encourage further research to clarify the role of obesity and overweight in the relationship between OSA and migraine, as well as the potential benefits of body weight control for those with these two comorbid conditions.

Objectives: To analyze headache and migraine dynamics around severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Background: Headache is a common symptom of SARS-CoV-2 infection, which caused the coronavirus disease 2019 (COVID-19) pandemic. However, the daily changes in headache patterns in patients with migraine during the infection are unclear.

Methods: This study is a post hoc and retrospective study of patients with migraine and documented COVID-19 diagnoses and headache diaries from a large prospective migraine cohort that consecutively enrolls eligible patients. Patients' characteristics, headache and migraine patterns, and vaccination data were retrieved. Change points in daily headache or migraine rates of this cohort were identified from 28 days before (day -28) to 28 days after (day 28) the infection. We calculated and compared the weekly headache and migraine days of individual patients during pre-infection, infection, and post-infection periods based on the change points. We further categorized patients into those with increased headache days and those without to investigate if vaccinations affected the headache patterns by comparing the pre- and post-infection headache days.

Results: A total of 463 patients, 370 (79.9%) females, with an age (mean ± standard deviation) of 41.5 ± 11.9 years, were enrolled. A total of 26,391 diary days were analyzed. The change-point algorithm identified changes in headache rates on day -4 (95% credible interval: -5.0, -1.2) and day 12 (95% credible interval: 7.6, 17.0). For migraine attacks, the change points were day -2 (95% credible interval: -4.9, -0.8) and day 11 (95% credible interval: 7.6, 17.2). After the grouping based on these change points, we found that the weekly headache days (mean ± standard error of the mean) increased from 1.5 ± 0.1 days during pre-infection to 1.8 ± 0.1 days during acute infection and recovered to 1.6 ± 0.1 days after infection. The weekly migraine days increased from 1.0 ± 0.1 day to 1.3 ± 0.1 days during acute infection and recovered to 1.1 ± 0.1 days. Female patients and those older than 40 had more abrupt changes in headache and migraine patterns. There was no impact of vaccinations on the headache pattern regardless of the type or dose of the vaccinations or the intervals between the last vaccination and the COVID-19 diagnosis.

Conclusion: We demonstrated that the headache and migraine rates among individuals with migraine escalated during the early stage of SARS-CoV-2 infection and returned to baseline along with systemic viral clearance.

Background: Dyspareunia and pelvic pain are commonly comorbid conditions with migraine, with chronic migraine potentially contributing to the exacerbation of sexual dysfunction and pain.

Methods: We conducted a retrospective cohort study of female patients seen at the Stanford Headache Clinic between January 1, 2022, and March 24, 2024, for the management of chronic migraine for dyspareunia and pelvic pain and stratified for comorbidities related to both conditions.

Results: Patients with chronic migraine were overall found to be at higher likelihood of having a comorbid pelvic pain condition after adjusting for age, race-ethnicity, and marital status (adjusted odds ratio [aOR] 2.46; 95% confidence interval [CI]: 2.17-2.79, p < 0.001), with interstitial cystitis (aOR 3.04; 95% CI: 1.98-4.66, p < 0.001), vaginismus (aOR 2.51; 95% CI: 1.29-4.88, p = 0.007), dyspareunia (aOR 1.97; 95% CI: 1.57-2.49, p < 0.001), and vulvodynia (aOR 1.88; 95% CI: 1.04-3.40, p = 0.036) all increased in the chronic migraine population. Furthermore, conditions that are commonly comorbid with migraine, such as irritable bowel syndrome, fibromyalgia, and mood disorders, independently contributed to increased risk of pelvic pain conditions and dyspareunia.

Conclusions: Conditions that cause pelvic pain and sexual dysfunction in women are disproportionally common in women with chronic migraine and may contribute to disability and difficulties in interpersonal relationships. Early screening for disorders of pelvic pain in patients with chronic migraine and appropriate referrals can improve the quality of life of these patients.

Objective: To investigate the association between adolescents' dietary quality and the presence of painful temporomandibular disorder (p-TMD) and headaches in young adulthood.

Background: P-TMD is a common orofacial pain condition often associated with headaches and discomfort. Some studies have shown that dietary behaviors can impact chronic musculoskeletal pain. Although various factors such as sex, age, psychosocial aspects, and pain sensitivity contribute to p-TMD, the role of nutrition remains unclear.

Methods: The dietary quality of 32,247 singletons from the Danish National Birth Cohort (DNBC) at age 14 was assessed using the Healthy Eating Index (HEI) encompassing eight domains. Among these, 11,982 (37.1%) individuals completed the TMD pain screener and headache-related queries at age 18 and above. HEI and dietary domains were analyzed as potential risk factors for p-TMD and headaches.

Results: P-TMD was present in 3163 of the 11,982 members of the study population. HEI scores were divided into quartiles, with quartile four indicating the highest dietary quality. Quartile four showed a higher odds ratio (OR) for p-TMD than quartile one (OR = 1.14 [95% confidence interval (CI), 1.01-1.29]), but the significance was lost after adjustment for confounders (adjusted OR [aOR] = 1.12 [95% CI, 0.97-1.30]). Overall dietary quality was not significantly associated with headaches. However, specific dietary quality domains, such as dietary fibers (aOR = 0.97 [95% CI, 0.95-0.99]), fish (aOR = 0.98 [95% CI, 0.97-1.00]), sodium (aOR = 1.03 [95% CI, 1.01-1.06]), and added sugar (aOR = 0.97 [95% CI, 0.95-0.99]) were associated with headaches but not with p-TMD after adjustment.

Conclusion: Overall adolescent dietary quality did not significantly associate with p-TMD or headaches in young adulthood after adjusting for confounders. However, specific dietary domains exhibited weak but statistically significant associations with headaches. These findings underscore the interplay between diet and pain, calling for further research to unveil the underlying pathophysiological mechanisms connecting lifestyle, p-TMD, and headaches.