{"title":"Association between headache frequency and risk for fibromyalgia in patients with migraine.","authors":"Yen-Hui Liao, Yi-Shiang Tzeng, Shih-Pin Chen, Yu-Hsiang Ling, Wei-Ta Chen, Shuu-Jiun Wang, Yen-Feng Wang","doi":"10.1177/03331024251317486","DOIUrl":"https://doi.org/10.1177/03331024251317486","url":null,"abstract":"<p><strong>Background: </strong>The present study aimed to evaluate the risk and impact of fibromyalgia in relation to headache frequency in migraine patients.</p><p><strong>Methods: </strong>This cross-sectional study involved migraine patients from a regional hospital and a tertiary medical center. Diagnoses of migraine and fibromyalgia were made according to the International Classification of Headache Disorders, 3rd edition, and the modified 2016 American College of Rheumatology diagnostic criteria, respectively. Clinical data, including Fibromyalgia Symptoms (FS) scale and revised Fibromyalgia Impact Questionnaire (FIQR), were collected systematically by questionnaires-based interviews. Patients were categorized based on monthly headache day (MHD) cut-offs derived from decision tree analysis based on the chi-squared automatic interaction detection algorithm.</p><p><strong>Results: </strong>The study involved 2082 migraine patients (1619 female/463 male, mean ± SD age 39.3 ± 12.0 years), including 132 with fibromyalgia (118 female/14 male, mean ± SD age 44.1 ± 12.7 years) (6.3%). Patients were divided into three groups: ≤9 MHDs (n = 924), 10-20 MHDs (n = 745) and ≥21 MHDs (n = 413). The percentage of fibromyalgia increased with headache frequency (<i>p</i> < 0.001). When compared with patients with ≤9 MHDs (2.8%), those with 10-20 MHDs (6.2%) (odds ratio (OR) = 1.90, 95% confidence interval (CI) = 1.11-3.23, <i>p</i> = 0.019) and ≥21 MHDs (14.5%) (OR = 3.68, 95% CI = 2.08-6.49, <i>p</i> < 0.001) were more likely to have fibromyalgia. Patients with more frequent headaches had higher FS and FIQR scores (all <i>p</i> < 0.001 between MHD categories).</p><p><strong>Conclusions: </strong>There was an independent dose-response association between headache frequency and odds, severity, and impact of fibromyalgia in migraine patients. For migraine patients with a higher headache frequency, the potential risk of comorbid fibromyalgia should not be overlooked given its association with more severe clinical manifestations and greater disability.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251317486"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CephalalgiaPub Date : 2025-02-01DOI: 10.1177/03331024251317127
{"title":"Thanks to Reviewers.","authors":"","doi":"10.1177/03331024251317127","DOIUrl":"https://doi.org/10.1177/03331024251317127","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251317127"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CephalalgiaPub Date : 2025-02-01DOI: 10.1177/03331024251320610
Peter J Goadsby, Tim P Jürgens, Elimor Brand-Schieber, Krisztian Nagy, Yingyi Liu, Ramesh Boinpally, Sven Stodtmann, Joel M Trugman
{"title":"Efficacy of ubrogepant and atogepant in males and females with migraine: A secondary analysis of randomized clinical trials.","authors":"Peter J Goadsby, Tim P Jürgens, Elimor Brand-Schieber, Krisztian Nagy, Yingyi Liu, Ramesh Boinpally, Sven Stodtmann, Joel M Trugman","doi":"10.1177/03331024251320610","DOIUrl":"https://doi.org/10.1177/03331024251320610","url":null,"abstract":"<p><strong>Background: </strong>Published evidence supporting efficacy of calcitonin gene-related peptide receptor antagonists as acute migraine treatments in males is limited.</p><p><strong>Methods: </strong>To fill the gap, we present male and female data from four ubrogepant and four atogepant randomized, double-blind, placebo-controlled trials for acute and preventive treatment of migraine, respectively. Acute outcomes included 2-h pain freedom and absence of most bothersome symptom (co-primary; headache-phase randomized, double-blind, placebo-controlled trials); absence of moderate-to-severe headache within 24 h (primary; prodrome randomized, double-blind, placebo-controlled trial). Preventive outcome included change from baseline in mean monthly migraine days across 12 weeks (primary).</p><p><strong>Results: </strong>Pooled data from phase 3 headache-phase ubrogepant randomized, double-blind, placebo-controlled trials showed similar rates of pain freedom (19.4% vs 21.1%) and absence of most bothersome symptom (35.1% vs 39.0%) 2 h post-dose between males and females, respectively. Time course of pain freedom and absence of most bothersome symptom over 48 h was similar between male and female subgroups. Comparable reductions in mean monthly migraine days across 12-week treatment periods were found between males and females treated with atogepant 60 mg once-daily in pooled episodic migraine and chronic migraine randomized, double-blind, placebo-controlled trials.</p><p><strong>Conclusion/interpretation: </strong>In ubrogepant and atogepant randomized, double-blind, placebo-controlled trials, although analysis power for males is limited due to small sample sizes, evidence supports similar treatment effects in males and females with migraine.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT02828020; NCT02867709; NCT04492020; NCT01613248; NCT02848326; NCT03777059; NCT04740827; NCT03855137.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251320610"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CephalalgiaPub Date : 2025-02-01DOI: 10.1177/03331024251321087
Edita Navratilova, Caroline M Kopruszinski, Janice Oyarzo, Kara R Barber, Trent Anderson, David W Dodick, Todd J Schwedt, Frank Porreca
{"title":"Sex differences in effectiveness of CGRP receptor antagonism for treatment of acute and persistent headache-like pain in a mouse model of mild traumatic brain injury.","authors":"Edita Navratilova, Caroline M Kopruszinski, Janice Oyarzo, Kara R Barber, Trent Anderson, David W Dodick, Todd J Schwedt, Frank Porreca","doi":"10.1177/03331024251321087","DOIUrl":"https://doi.org/10.1177/03331024251321087","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) commonly elicits acute (APTH) and/or persistent (PPTH) post-traumatic headache. Calcitonin gene related peptide (CGRP) has been implicated as a contributor to PTH pathophysiology. We explored the possibility of sexual dimorphism in the effects of CGRP receptor (CGRP-R) blockade in a preclinical model of PTH induced by a mild TBI (mTBI) in male or female mice.</p><p><strong>Methods: </strong>Mice were lightly anesthetized and placed on a tissue paper stage prior to receiving a sham procedure or mTBI resulting from a closed-head weight drop injury. Behavioral responses to periorbital and hindpaw tactile (von Frey filaments) or thermal (hot plate) stimuli over the first 14 days post-mTBI were evaluated as measures of APTH. The PPTH phase was studied following the resolution of mTBI-induced APTH at days 14 and 28. PPTH was precipitated by exposure to bright lights (i.e., bright light stress, BLS). Olcegepant was delivered subcutaneously either repeatedly beginning 2 h after mTBI to produce a sustained block of CGRP-R signaling across the APTH phase, or as a single administration on days 14 or 28 post-mTBI to evaluate possible effects during the PPTH phase.</p><p><strong>Results: </strong>mTBI, but not sham-procedure, produced periorbital and hindpaw tactile allodynia, as well as thermal hypersensitivity in mice of both sexes. APTH-related hypersensitivity was transient and resolved by day 14 post-injury. No sex differences were observed in the magnitude or duration of APTH-related pain behaviors. Sustained CGRP-R blockade was, however, significantly more effective in female than male mice in inhibiting pain behaviors in the APTH phase and in preventing the emergence of BLS-induced PPTH. CGRP-R blockade following the resolution of mTBI-induced APTH pain behaviors, on either day 14 or 28, minimally altered BLS-induced PPTH in either sex.</p><p><strong>Conclusions: </strong>Sustained CGRP-R blockade starting soon after mTBI significantly inhibited APTH and prevented the expression of PPTH with greater analgesic effects in females compared to males. Delayed CGRP-R blockade beginning after resolution of APTH phase was minimally effective in preventing expression of PPTH in either sex. These data are consistent with previous observations that CGRP induces pain behaviors preferentially in females. Early and continuous CGRP blockade following mTBI may represent a viable treatment option for PTH treatment and the prevention of PTH persistence, especially in females.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251321087"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CephalalgiaPub Date : 2025-02-01DOI: 10.1177/03331024241313377
Edina Szabo, Nicolas R Bolo, David Borsook, Rami Burstein, Sait Ashina
{"title":"Peripherally acting anti-CGRP monoclonal antibodies attenuate cortical resting-state connectivity in migraine patients.","authors":"Edina Szabo, Nicolas R Bolo, David Borsook, Rami Burstein, Sait Ashina","doi":"10.1177/03331024241313377","DOIUrl":"https://doi.org/10.1177/03331024241313377","url":null,"abstract":"<p><strong>Background: </strong>In about half of migraine patients, anti-calcitonin gene-related peptide monoclonal antibodies reduce monthly migraine days by >50%. In these patients, this class of drugs may change cortical functions by decreasing nociceptive afferent barrage. This prospective study investigated functional connectivity changes in treatment responders after three-month treatment with galcanezumab.</p><p><strong>Methods: </strong>Resting-state functional magnetic resonance imaging data were acquired for patients with high-frequency episodic or chronic migraine (<i>N </i>= 36) before and after treatment. Of these, 19 patients were classified as treatment responders (≥50% reduction in monthly migraine days) and 17 were considered non-responders (<50% reduction). Functional connectivity across cortical regions was assessed using a region-of-interest (ROI)-to-ROI analysis approach.</p><p><strong>Results: </strong>At baseline, there were no significant differences between treatment responders and treatment non-responders. In the treatment responder group, reduced functional connectivity was observed after treatment between regions of the primary somatosensory and motor cortices, insula, and several occipital and temporo-occipital areas (within the visual network). In contrast, no such changes were seen in the non-responder group.</p><p><strong>Conclusion: </strong>These findings suggest that even a relatively short period of reduced nociceptive signals may be sufficient to initiate a cortical recovery process in which its resting hyperexcitable mode shifts to a less excitable state.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024241313377"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CephalalgiaPub Date : 2025-02-01DOI: 10.1177/03331024251317606
Andreas R Gantenbein
{"title":"Depression screening in migraine - A double-edged sword.","authors":"Andreas R Gantenbein","doi":"10.1177/03331024251317606","DOIUrl":"https://doi.org/10.1177/03331024251317606","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251317606"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CephalalgiaPub Date : 2025-02-01DOI: 10.1177/03331024251317446
Gege Guzman, Caroline M Kopruszinski, Kara R Barber, Robson C Lillo Vizin, David W Dodick, Edita Navratilova, Frank Porreca
{"title":"Chronification of migraine sensitizes to CGRP in male and female mice.","authors":"Gege Guzman, Caroline M Kopruszinski, Kara R Barber, Robson C Lillo Vizin, David W Dodick, Edita Navratilova, Frank Porreca","doi":"10.1177/03331024251317446","DOIUrl":"https://doi.org/10.1177/03331024251317446","url":null,"abstract":"<p><strong>Background: </strong>Acute therapies targeting calcitonin gene-related peptide (CGRP) for episodic migraine (EM) demonstrate efficacy in women, but evidence of efficacy in men remains to be established. By contrast, CGRP targeting therapies for migraine prevention are effective in both men and women with frequent EM or chronic migraine (CM). Preclinical studies have shown that supradural application of CGRP preferentially produces migraine-like pain behaviors in female rodents. We hypothesized that, in male mice, increased frequency of migraine-like pain may sensitize to nociceptive effects of CGRP and this might be associated with altered expression of CGRP in trigeminal ganglion (TG) neurons and/or in their dural projections.</p><p><strong>Methods: </strong>CM was modeled in male and female mice by repeated administration of nitroglycerin (NTG). Medication overuse headache (MOH), a form of CM, was modeled by repeated daily administration of sumatriptan. Following resolution of transient cutaneous allodynia (CA) elicited by NTG or sumatriptan, mice received a sex specific subthreshold dose of supradural CGRP that does not elicit CA in naïve male or female mice, and CA was evaluated. CGRP-positive cell bodies in the ophthalmic V1 region of the trigeminal ganglion (TGV1) and CGRP-positive nerve fibers innervating the dura mater were assessed.</p><p><strong>Results: </strong>Supradural administration of 1 pg of CGRP produced migraine-like pain behaviors in female, but not male, mice; a ten-fold lower dose was established as subthreshold in naïve female mice. Repeated NTG or sumatriptan produced transient CA in both female and male mice that resolved within 8-11 days after treatment cessation. Following resolution of CA, previously subthreshold doses of CGRP elicited CA in CM and MOH models in mice of both sexes, with no effects observed in vehicle treated controls. A higher number of CGRP-positive neurons in the TGV1 was found in naïve female compared to male mice. The number of CGRP-positive TGV1 neurons was increased in both sexes following repeated NTG. Similar nerve fiber density was observed in the dura mater of male and female mice and no differences were detected following repeated NTG.</p><p><strong>Conclusions: </strong>As previously reported, CGRP produced female-selective migraine-like pain behaviors in naïve mice. Consistent with behavioral effects, female mice demonstrated a higher number of CGRP-positive cells in the TGV1. These findings appear relevant to clinical observations of female efficacy of CGRP-receptor antagonists for acute treatment in EM patients. In models of CM or MOH that are characterized by increased frequency of migraine-like pain, previously subthreshold doses of supradural CGRP now elicited migraine-like nociceptive behaviors in mice of both sexes. The increased pain responses were accompanied by increased number CGRP positive TGV1 cells in the NTG model in both female and male mice. These data suggest ","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251317446"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"OnabotulinumtoxinA for primary new daily persistent headache and comparison to chronic migraine.","authors":"Sanjay Cheema, Susie Lagrata, Khadija Rerhou Rantell, Maha Ahmed, Salwa Kamourieh, Manjit Singh Matharu","doi":"10.1177/03331024251317448","DOIUrl":"https://doi.org/10.1177/03331024251317448","url":null,"abstract":"<p><strong>Background: </strong>New daily persistent headache (NDPH) is an often treatment-refractory primary headache disorder with a lack of evidence base for treatment.</p><p><strong>Methods: </strong>We performed an observational study using prospectively collected data in consecutive patients with NDPH, chronic migraine with daily headache (daily-CM) and without daily headache (non-daily-CM). Patients were treated with two cycles of OnabotulinumtoxinA. Propensity score matching was used to control for imbalances between the groups. The primary outcome measure was the proportion who experienced a ≥ 30% improvement in monthly moderate-to-severe headache days at 24 weeks.</p><p><strong>Results: </strong>We included 58 patients with NDPH, 148 with daily-CM, and 84 with non-daily-CM. In NDPH, 34.5% of patients experienced a ≥ 30% improvement in monthly moderate-to-severe headache days, compared to 43.2% in daily-CM and 51.2% in non-daily CM. In NDPH, 6.9% experienced an improvement in monthly headache days, 27.6% an improvement in headache severity, 25.9% a ≥ 6 point improvement in HIT-6 score, and 59% a patient reported improvement. There was no significant difference in response rates between the three groups. Adverse event rates were similar in all groups and there were no serious adverse events.</p><p><strong>Conclusion: </strong>OnabotulinumtoxinA is effective in approximately 1/3 patients with NDPH and has a favourable safety profile.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251317448"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methodological challenges in using screening tools for depression in migraine: A systematic review.","authors":"Jasmin Asheer, Fatima Ali, Rikke Hilker, Poul Videbech, Henrik Winther Schytz","doi":"10.1177/03331024251317635","DOIUrl":"https://doi.org/10.1177/03331024251317635","url":null,"abstract":"<p><strong>Background: </strong>Depression is frequently described to occur in migraine, and depression screening questionnaires are commonly used to evaluate depressive symptoms in patients with migraine. The present study aimed to investigate how the most common depression screening tools are used in migraine studies to determine whether they are applied and interpreted correctly.</p><p><strong>Methods: </strong>PubMed was systematically searched, and we included any study using the Beck Depression Inventory (BDI), Patient Health Questionnaire-9 (PHQ-9), Hospital Anxiety Depression Scale (HADS) or Hamilton Depression Rating Scale (HAM-D). The study included adults diagnosed with migraine based on the International Classification of Headache Disorders (ICHD-2 or ICHD-3).</p><p><strong>Results: </strong>The literature search generated 78 studies. Thirty-five (45%) of the included studies used a depression screening tool as evidence of depression. This applied to 53, 46, 47 and 13% of studies using PHQ, BDI, HADS and HAM-D, respectively. Only one study out of 35 confirmed the diagnosis with a diagnostic interview. The data presentation and interpretation across the studies was highly heterogeneous.</p><p><strong>Conclusions: </strong>Screening tools as evidence of depression in patients with migraine may lead to inaccurate estimates of depression among migraine patients. There is a need for guidelines on and validation of depression screening tools in patients with migraine.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251317635"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}