Cephalalgia最新文献

{"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205852/pdf/","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":"OA","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":"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":"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}

{"title":"Combined effects of cannabidiol and Δ9-tetrahydrocannabinol alleviate migraine-like symptoms in mice.","authors":"Erik Zorrilla, Georgii Krivoshein, Adisa Kuburas, Maarten Schenke, Cassandra L Piña, Sandra H van Heiningen, Jayme S Waite, Anisa Dehghani, William C Castonguay, Harold C Flinn, Arn M J M van den Maagdenberg, Andrew F Russo, Else A Tolner, Anne-Sophie Wattiez","doi":"10.1177/03331024251314487","DOIUrl":"10.1177/03331024251314487","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic use of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to treat migraine has been understudied. Using three mouse models, we examined the impact of CBD and THC on migraine-relevant behaviors triggered by: 1) calcitonin gene-related peptide (CGRP), 2) sodium nitroprusside (SNP), and 3) cortical spreading depolarization (CSD).</p><p><strong>Methods: </strong>Both male and female CD1 mice were treated with CBD (100 mg/kg) or THC (1 mg/kg) alone or in combinations of CBD (1, 30 or 100 mg/kg) and THC (1 mg/kg) prior to injection of CGRP or SNP. The mice were assessed for light aversion (photophobia), squint (non-evoked pain), and periorbital tactile hypersensitivity, as well as possible adverse effects. In a separate set of experiments, CSD events were optogenetically induced in familial hemiplegic migraine 1 (FHM1) mutant and wildtype littermates (WT) mice (C57BL/6 background), followed by grimace and motor assessments with and without combinations of CBD (30 or 100 mg/kg) and THC (1 mg/kg).</p><p><strong>Results: </strong>In CD1 mice, a 100:1 CBD:THC combination mitigated light aversion induced by CGRP and SNP in males and females. Rescue of CGRP- and SNP-induced squint was observed only in male mice with 100:1 CBD:THC. None of the treatments rescued periorbital tactile hypersensitivity in either sex. In FHM1 mutant and WT mice, the 100:1 CBD:THC ratio did not affect CSD characteristics but did reduce CSD-induced grimace features (i.e., head pain mimic). No adverse effects of any of the cannabinoid treatments were observed using cognitive, emotional, or motor tests.</p><p><strong>Conclusions: </strong>A 100:1 ratio of CBD:THC has a beneficial effect on some of the most bothersome migraine-related symptoms in three mouse models. Our findings support a potential therapeutic efficacy of combined CBD and THC treatments.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251314487"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482350","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":"The Jes Olesen awards for the advancement of headache medicine.","authors":"Cristina Tassorelli, Timothy J Steiner","doi":"10.1177/03331024251318563","DOIUrl":"https://doi.org/10.1177/03331024251318563","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251318563"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448391","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":"Setting higher standards for migraine prevention: A position statement of the International Headache Society.","authors":"Simona Sacco, Messoud Ashina, Hans-Christoph Diener, Faraidoon Haghdoost, Mi Ji Lee, Teshamae S Monteith, Bronwyn Jenkins, Mario F P Peres, Patricia Pozo-Rosich, Raffaele Ornello, Francesca Puledda, Fumihiko Sakai, Todd J Schwedt, Gisela Terwindt, Gloria Vaghi, Shuu-Jiun Wang, Fayyaz Ahmed, Cristina Tassorelli","doi":"10.1177/03331024251320608","DOIUrl":"10.1177/03331024251320608","url":null,"abstract":"<p><p>Migraine is one of the most prevalent and disabling neurological diseases, significantly affecting quality of life and productivity, as well as contributing to substantial societal costs. Recent innovations, including calcitonin gene-related peptide (CGRP) pathway inhibitors and onabotulinumtoxinA, have transformed migraine prevention by offering high efficacy and excellent tolerability, thus improving adherence. Clinical trials and real-world studies show that significant reductions in migraine frequency and, in some cases, complete migraine freedom is achievable. In this Position Statement, we advocate for raising the standards of migraine prevention by setting ambitious treatment goals aimed at optimal outcomes, such as migraine freedom or very low number of days with migraine or moderate/severe headache. We emphasize the importance of addressing residual migraine burden, highlighting that achieving a ≥50% reduction in monthly migraine days, although often considered a successful response, may not fully restore quality of life. Relying solely on percentage-based improvements can obscure the persisting impact of residual burden. This Position Statement does not want to change the standards for clinical trials but aims primarily at real-world clinical practice and proposes a shift from percentage-based measures of success to absolute goals while on treatment. We outline a framework that categorizes outcomes into four tiers: migraine freedom (no days with migraine or moderate-to-severe headache), optimal control (less than four days with migraine or moderate-to-severe headache), modest control (four to six days with migraine or moderate-to-severe headache) and insufficient control (more than days with migraine or moderate-to-severe headache). Focusing on residual burden while on treatment aims to further improve patient quality of life and drive innovation in preventive therapies and non-pharmacological approaches. By advocating for higher standards, this Position Statement, is not aimed primarily to drive reimbursement policies for migraine preventive treatments, but seeks to inspire clinicians, researchers and policymakers to prioritize ambitious goals in migraine prevention, ultimately enhancing patient outcomes and reducing the broader societal and economic impact of this debilitating condition.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 2","pages":"3331024251320608"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467100","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":"Defining the typical characteristics of orthostatic headache in patients with spontaneous intracranial hypotension.","authors":"Dwij Mehta, Sanjay Cheema, Sophie Glover, Ayman M Qureshi, Indran Davagnanam, Salwa Kamourieh, Parag Sayal, Ahmed Toma, Susie Lagrata, Clare Joy, Callum Duncan, Jane Anderson, Brendan Davies, Paul J Dorman, Heather Angus-Leppan, James Walkden, Jonathan Rohrer, Manjit S Matharu","doi":"10.1177/03331024241308154","DOIUrl":"https://doi.org/10.1177/03331024241308154","url":null,"abstract":"<p><strong>Background: </strong>Orthostatic headache (OH) is a common feature of various conditions, including spontaneous intracranial hypotension (SIH), but no precise definition currently exists outlining the typical OH characteristics. This ambiguity risks misdiagnosis with unnecessary investigations and delay in institution of treatment. The present study aimed to carry out structured phenotyping of OH in patients with SIH with the aim of outlining its typical characteristics.</p><p><strong>Methods: </strong>Eligible patients with clinico-radiological confirmed SIH underwent a structured interview, after which a specialist interest group utilised the modified Delphi process to analyse the data and achieve consensus on defining the typical characteristics of OH in SIH.</p><p><strong>Results: </strong>In total, 137 patients were recruited. OH was present in 75.9%. Typical OH characteristics in SIH were defined as having a baseline severity (lying flat) on waking up of ≤3 (0-10, verbal response scale), headache onset-time of ≤4.5 h on becoming upright, time to peak severity of ≤7.5 h and an offset to baseline severity within 1.5 h of recumbency. Intra-individual consistency in the onset and offset-time was deemed a necessary characteristic.</p><p><strong>Conclusions: </strong>Defining typical OH characteristics has the potential of enhancing SIH diagnostics and management, at the same time as minimising unwarranted invasive procedures.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 1","pages":"3331024241308154"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945689","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":"Impact of CGRP monoclonal antibody treatment on blood pressure in patients with migraine: A systematic review and potential clinical implications.","authors":"Britt W H van der Arend, Floor C van Welie, Michael H Olsen, Jan Versijpt, Antoinette Maassen Van Den Brink, Gisela M Terwindt","doi":"10.1177/03331024241297673","DOIUrl":"10.1177/03331024241297673","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or the CGRP-receptor have revolutionized the prevention of migraine. Despite their effectiveness, worries have surfaced regarding potential unwanted cardiovascular effects linked to the vasodilation function of CGRP, suggesting a potential influence on blood pressure (BP).</p><p><strong>Methods: </strong>Studies were systematically retrieved from PubMed, Cochrane Database of Systematic Reviews, Web of Science, MEDLINE and EMBASE up to 1 May 2024. We focused on randomized controlled trials and observational cohort or case-control studies examining the impact of anti-CGRP(R)-monoclonal antibodies (mAbs) compared to control treatments on BP in patients with migraine. Two reviewers independently conducted study selection, data extraction and risk of bias assessment.</p><p><strong>Results: </strong>The literature search yielded 693 articles. After removing duplicates and conducting screening, 22 full-text articles were evaluated, with only four studies meeting the inclusion criteria. Among these, only one study had a low risk of bias and reported elevated BP following initiation of anti-CGRP(R)-mAb treatment.</p><p><strong>Conclusions: </strong>Although anti-CGRP(R)-mAbs offer substantial benefits for migraine prevention, the potential risk of increased BP requires attention. Despite the current limited evidence, clinicians are urged to monitor BP of migraine patients undergoing treatment with anti-CGRP(R)-mAbs and to remain aware of the increased risk of cardiovascular events in these patients.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 1","pages":"3331024241297673"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057960","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":"Migraine and its major subtypes - with and without aura are associated with polygenic scores for autism.","authors":"Salahuddin Mohammad, Giorgia Bussu, Gull Rukh, Helgi B Schiöth, Jessica Mwinyi","doi":"10.1177/03331024241312666","DOIUrl":"10.1177/03331024241312666","url":null,"abstract":"<p><strong>Background: </strong>Individuals with autism spectrum disorder (ASD) experience a wide array of neurological, psychiatric and medical comorbidities, yet little attention has been given to the potential link between ASD and migraine, one of the most prevalent neurological disorders worldwide. This study aimed to investigate whether a genetic predisposition for ASD is linked to migraine and its major subtypes, with and without aura. Additionally, potential moderator and mediators of the association between ASD and migraine were explored.</p><p><strong>Methods: </strong>Polygenic scores (PGS) for ASD were constructed based on the genome-wide association study by the Psychiatric Genomics Consortium, on the UK Biobank cohort dataset comprising 337,386 participants using PRSice-2. Regression analyses were performed to investigate the association of ASD PGS with migraine and its major subtypes, with and without aura. Sex was explored as a potential moderating factor. The mediation analyses took into consideration variables such as education, personality trait neuroticism, body mass index (BMI) and four categories of comorbidities (psychiatric, vascular, neurologic and others).</p><p><strong>Results: </strong>ASD PGS were significantly and positively associated with migraine (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.02-1.05, <i>p </i>< 0.002), migraine without aura (OR = 1.05, 95% CI = 1.02-1.07, <i>p </i>< 0.002) and migraine with aura (OR = 1.05, 95% CI = 1.02-1.07, <i>p </i>< 0.002). No moderating effect of sex on the association between ASD PGS and migraine was observed. As for potential mediators, only the personality trait neuroticism significantly mediated the association between ASD PGS and migraine, with the proportion of effect mediated 8.75% (95% CI = 4-18%).</p><p><strong>Conclusions: </strong>Our study suggests that individuals genetically predisposed to autism are at higher risk of experiencing migraine, including the two major subtypes, with and without aura. While emphasizing the complex shared genetic and pathophysiological interactions of these conditions, the role of personality trait neuroticism as a mediator of this relationship is highlighted.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 1","pages":"3331024241312666"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000734","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":"Sex differences in photophobic behaviors following cortical spreading depression in rats.","authors":"Manvir Kaur, Nicholas A Ward, Kelly L Karlage, Catherine W Morgans, Sue A Aicher, Tally M Largent-Milnes","doi":"10.1177/03331024241310550","DOIUrl":"10.1177/03331024241310550","url":null,"abstract":"<p><strong>Purpose: </strong>Photophobia is a common and debilitating symptom associated with migraine. Women are disproportionately affected by migraines, with a higher prevalence and more severe symptoms compared to men. This study investigated the effects of cortical spreading depression on light-aversive and dark-seeking behaviors in a rat model, with an emphasis on sex differences.</p><p><strong>Method: </strong>Experiments were conducted on seven to eight-week-old male and female Sprague Dawley rats. cortical spreading depression was modeled by injections of potassium chloride or artificial cerebrospinal fluid into the occipital cortex through a guide cannula. Key behavioral assessments included light-aversive and dark-seeking behaviors measured using a three-chamber box, pupil to iris ratio, periorbital tightening, periorbital allodynia and facial withdrawal thresholds.</p><p><strong>Results: </strong>Our results demonstrated that cortical potassium chloride injections significantly increased photophobic behaviors, particularly in female rats. Specifically, potassium chloride-injected females demonstrated a significant reduction in the time spent in the light chamber (p = 0.001) and increased time in the dark chamber compared to control rats (p = 0.01), indicating heightened light-aversion. Females exhibited more substantial pupil constriction and eyelid closure at 180 min after potassium chloride injection compared to artificial cerebrospinal fluid injection, suggesting a stronger physiological response to light. Similarly, a greater percent of female rats displayed periorbital allodynia (withdrawal threshold <6 g) over a post injection time course compared to male rats. Among rats that exhibited periorbital allodynia at least two consecutive time points, females had significantly lower facial withdrawal thresholds than males at 60-, 90-, 120-, and 180-min post injection (p < 0.05), suggesting a difference in magnitude and duration. Furthermore, the area under the curve for the time course experiment indicated development of tactile allodynia in periorbital region among female rats (p < 0.0001).</p><p><strong>Conclusion: </strong>Altogether these findings highlight the importance of considering sex-specific differences in developing therapeutic strategies for the treatment of migraine. We report for the first time a complete time course analysis of migraine-related responses, providing a comprehensive overview of the dynamics involved. The results suggest that potassium chloride-induced cortical spreading depression may offer a valuable model for studying the underlying mechanisms and sex differences of photophobia in migraine, aiding in the development of targeted treatments.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 1","pages":"3331024241310550"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945693","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}