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Background: Vestibular migraine (VM) is a disorder characterized by recurrent episodes of dizziness or vertigo and is often accompanied by headache. The mechanisms underlying vestibular dysfunction and pain in VM remain unclear. Methods: Chronic migraine (CM) and VM models were induced by NTG and kainic acid, respectively. Behavioral assessments were conducted to evaluate vestibular dysfunction and pain in the VM and CM models. Transmission electron microscopy (TEM) was used to examine peripheral receptor impairment. Immunofluorescence, including staining for Cellular Proto-oncogene (c-Fos), Neuronal Nuclei (NeuN), and calcitonin gene-related peptide (CGRP), identified activated brain regions such as the cortex, midbrain, and cerebellum. Multiplex immunohistochemistry and cholera toxin subunit B (CTB) tracing were performed to analyze nuclear heterogeneity and neural communication. Additionally, RNA sequencing (RNA-Seq) and Ionized calcium-binding adapter molecule 1 (IBA1) immunostaining were used to investigate ion channel expression in the spinal trigeminal nucleus caudalis (Sp5c). Results: CM and VM-related behaviors, such as allodynia and balance disturbance, were successfully reproduced in mouse model. TEM revealed significant damage to peripheral sensory receptors, particularly in the trigeminal ganglion and cochlear cells. Distinct activation patterns of c-Fos and CGRP were observed in VMs and CMs. CTB tracing confirmed that signals are transmitted from the vestibulocerebellum (VbC) to the Sp5c via the vestibular nuclei (VN). Furthermore, RNA-Seq combined with coimmunostaining revealed an increased expression of transient receptor potential vanilloid 2 (TRPV2) ion channels in microglia within Sp5c, indicating their potential role in VM pathology. Conclusions: This study preliminarily explored VbC-VN-Sp5c communication and identified TRPV2 ion channels in microglia as key players in neuron-glia crosstalk in VM. These findings provide new insights into the mechanisms underlying vestibular migraine and suggest potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Introductıon: Long-reported dual comorbidity between migraine and sleep disorders suggests that some gene variations may play a role in this relationship. Our previous study found an association between poor sleep quality and the G allele of the hypocretin receptor 1 (HCRTR1) rs2271933 gene in patients with chronic migraine (CM). This study aimed to examine the relationship of this gene with some sleep parameters. Methods: The present study was designed cross-sectional in the Mersin University Neurology Clinic between January 2000 and February 2018. Patients aged 18–75 years with CM according to the International Classification of Headache Disorders-3 (ICHD-3) criteria were included. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of the patients. Patients were divided into two groups according to PSQI scores <6 or ≥6. Genotyping was performed for the HCRTR1 rs2271933 gene. Results: Among the 100 patients with CM, only the data of those (n=67) with poor sleep quality were included in this study. The mean age of patients was 40.9±11.8%, and the female rate was 89.6%. We detected that increasing the time to fall asleep (p=0.369) and the rate of poor sleep quality (p=0.461) and also shortening sleep duration (p=0.016) with the increase of G allele carrier of HCRTR1 rs2271933 gene. Conclusıon: As the G allele carrier of the HCRTR1 rs2271933 gene increased, a shorter sleep duration was observed. This finding may contribute to studies on the physiological roles of orexins. [ABSTRACT FROM AUTHOR]

Objectives: Migraine represents the prevailing form of primary headache with no fully described etiology and pathophysiology. This study aimed to assess the association between vitamin B12 serum levels and both chronic and episodic migraine. Patients and methods: This study was conducted as a case-control study, including 90 migraineurs, divided into 48 with episodic migraine and 42 with chronic migraine as the case group, and 90 matched healthy participants as the control group. The serum level of vitamin B12 was measured using enzyme-linked immunosorbent assay (ELISA) for all subjects. Its association with the Migraine Disability Assessment (MIDAS) scale and migraine attack severity, measured using the Visual Analog Scale (VAS), was analyzed. Results: Migraineurs exhibited a notable reduction in serum vitamin B12 levels compared to the control group (243.97 ± 124.85 pg/ml vs. 302.69 ± 143.69 pg/ml, p = 0.014). Furthermore, chronic migraine patients had significantly lower serum vitamin B12 levels when compared to episodic migraine patients (202.7 ± 75.62 pg/ml vs. 269.17 ± 143.31 pg/ml, p = 0.026). A significant negative correlation was found between serum vitamin B12 levels and the severity of migraine attacks, as measured by the VAS (r = -0.407, p = 0.036). Conclusion: The current study highlighted that vitamin B12 deficiency is highly associated with migraine and its severity. Further interventional research is highly recommended to investigate the potential causality of this association. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction and inflammation are linked to migraine, which may contribute to atherogenesis and increase the risk of ischemia. In migraineurs, preclinical vascular involvement manifested as compromised structural characteristics of vessel wall has not received enough attention or evaluation. Objectives: To measure plasma pentraxin 3 as an indicator of endothelial dysfunction in migraine in comparison to controls and to examine its correlation with clinical characteristics, headache severity, and brain magnetic resonance imaging findings. Subjects and methods: This study was conducted on 40 migraineurs and 40 healthy matched control subjects. The severity and intensity of headaches were quantified using the Headache Impact Test and the translated Arabic version of Migraine Disability assessment questionnaires. Both patients and controls underwent routine laboratory assessment, brain MR imaging, and measurement of plasma pentraxin 3 level. Results: Patients with migraine had a significantly higher mean plasma pentraxin 3 when compared to controls. Patients with chronic migraine and those taking ergots also had significantly higher plasma pentraxin 3 levels. Additionally, there were statistically significant positive correlation between frequency of headaches and duration of the disease with plasma pentraxin 3 level. For diagnosing endothelial dysfunction in migraine patients, the sensitivity and specificity of pentraxin 3 levels were 85% and 95%, respectively, with cut-off value of 3.100 ng/ml. Conclusion: Pentraxin 3 levels could be used as a chemical biomarker for endothelial dysfunction in migraines with high sensitivity and specificity. Higher plasma levels of pentraxin 3 in patients receiving ergots may influence the selection of treatment for migraine patients. [ABSTRACT FROM AUTHOR]

Background: Medication-overuse headache (MOH) is the most common secondary headache disorder, resulting from or leading to the frequent use of acute headache medications. Despite the availability of various treatment strategies, the optimal approach remains uncertain. Objective: This network meta-analysis (NMA) aimed to evaluate the comparative efficacy of different strategies for managing MOH, focusing on reducing monthly headache days. Methods: We systematically reviewed randomized controlled trials (RCTs) comparing withdrawal strategies, including bridging therapies, the use of concurrent migraine prevention drugs, and additional education, in adult patients diagnosed with MOH. The primary outcome was the reduction in monthly headache days. Eligible studies were analyzed using a random-effects NMA model, integrating both direct and indirect evidence. Treatments were ranked using p-scores, and risk of bias was assessed using the Cochrane risk of bias tool 2.0. Results: Sixteen RCTs involving 3,000 participants were included. Compared to control, combination therapies, such as abrupt withdrawal with oral prevention and greater occipital nerve block and restriction of overused acute medication with oral prevention and Calcitonin gene-related peptide (CGRP) therapies, demonstrated the greatest efficacy, with reductions in monthly headache days of -10.6 (95% CI: [-15.03; -6.16]) and -8.47 (95% CI: [-12.78; -4.15]), respectively. Headache prevention strategies, including oral prevention (P), anti-calcitonin gene-related peptide (receptor) (CGRP(R)) therapies (A), and botulinum toxin (B) showed significant in reduction of monthly headache days, but no single initial prevention strategy demonstrates superior efficacy over the others. In contrast, abrupt withdrawal alone (W) showed no significant efficacy, with a mean difference of -2.77 (95% CI: [-5.74; 0.20]). Conclusion: Combination therapies, including anti-CGRP(R) therapies and nerve blocks, appear to be the most effective strategies for MOH management, highlighting their potential as initial treatment options. While headache prevention strategies demonstrated similar efficacy, abrupt withdrawal alone was insufficient. The observed reduction in headache frequency after treatment suggests that strategies with greater efficacy may help lower the likelihood of MOH relapse. Trial registration: PROSPERO, CRD 42024620487. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to discuss about the potential roles of neuropsychological instruments and tasks in the evaluation of dependence behaviors shared by medication-overuse headache (MOH) and substance use disorders (SUDs). Recent Findings: Recent studies utilizing criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM) for SUDs have revealed that MOH patients often exhibit impaired control over medication use, along with tolerance and withdrawal symptoms. In addition, dependence questionnaires such as the Leeds Dependence Questionnaire and the Severity of Dependence Scale have shown a strong correlation between MOH and higher dependence scores, with predictive value for treatment outcomes. Furthermore, investigations into decision-making processes with the Iowa Gambling Task have suggested potential parallels between MOH and SUDs. MOH patients exhibit biased decision-making, particularly in conditions of ambiguity, possibly predisposing them to favor immediate pain relief over long-term consequences. This suggests a potential mechanism involving emotional feedback processing in MOH. Summary: This review underscores the importance of recognizing dependence-like behaviors in MOH patients and highlights the potential utility of neuropsychological instruments and tasks in advancing the understanding of MOH pathophysiology. The findings suggest that MOH shares characteristics with substance dependence, emphasizing the need for tailored interventions in MOH management. Understanding the neurobehavioral aspects of MOH may lead to more effective therapeutic strategies aimed at mitigating dependence and improving long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine is a prevalent and potentially debilitating neurological disorder that is often comorbid with mental health conditions (such as anxiety and depression), but the underlying mechanisms linking these conditions remain poorly understood. Indoleamine 2,3-dioxygenase 1 (IDO1) has been implicated in inflammatory processes, including neuroinflammation and pain. However, its role as a link between neuroinflammation and pain sensitization in chronic migraine is not well defined. Methods: Male mice were used to establish a model of chronic migraine by recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg). Using pharmacological approaches, transgenic strategies and adeno-associated virus (AAV) intervention, we investigated the role of IDO1 in pain sensitization and migraine-related mood disorders in an NTG-induced chronic migraine mouse model. We employed a combination of immunoblotting, immunohistochemistry, three-dimensional reconstruction, RNA sequencing, electrophysiology, in vivo fiber photometry, and behavioral assays to elucidate the underlying mechanisms involved. Results: Our findings demonstrated that pharmacological inhibition and genetic knockout of IDO1 significantly alleviated pain sensitivity in a chronic migraine model. Neuronal activity in the anterior cingulate cortex (ACC) was evaluated with in vitro c-Fos immunostaining as well as in vivo fiber photometry, and a shift in the excitation/inhibition (E/I) balance toward excitation was observed through whole-cell patch clamp recording. Notably, IDO1 expression was increased in the ACC, and AAV-mediated IDO1 knockdown in the ACC rescued pain sensitivity, electrophysiological E/I balance changes, and anxiety-like behavior in chronic migraine model mice. Furthermore, IDO1 regulated microglial activation and pruning of neuronal synapses in the ACC. IDO1's microglial pruning function appears to be mediated through the interferon (IFN) signaling pathway, and the behavioral changes induced by IDO1 knockdown in the ACC could be reversed by activating this pathway. Conclusions: Our findings revealed that microglial IDO1 in the ACC drives pain sensitization and anxiety in chronic migraine, highlighting IDO1 as a potential therapeutic target for chronic migraine treatment. [ABSTRACT FROM AUTHOR]

Background: Fremanezumab was the third CGRP antibody available in our hospital. This examination of our experience with fremanezumab is focused on identifying the predictors of response. Methods: This was a prospective observational study in which we included high-frequency episodic/chronic migraine (HF/CM) patients who were prescribed fremanezumab during the year 2023. Our research involved collecting data on their demographic details, diagnoses made, treatments received, prophylactic measures taken in the past, and any comorbid conditions present. The number of headaches was documented for one quarter prior to and after the initiation of fremanezumab. Results: Eighty-nine patients received fremanezumab (86.5% female, 45.8 ± 12.5 years old, 70.1% naive). The headache days decreased from 21.1 ± 7.6 to 12.4 ± 11.2 days during the initial three months of the treatment, and a total of 55 patients (61.8%) exhibited a response rate of ≥50%. Six out of ten patients refractory to erenumab for at least 6 months responded to fremanezumab. Totals of 17 and 26 patients had been treated at least with galcanezumab or erenumab. The elements influencing non-response were as follows: prior failure to respond to both erenumab and galcanezumab (p < 0.0001), HF/CM length (11.9 ± 7.1 years in non-responders vs. 5.8 ± 4.8 in responders; p < 0.001), the presence of fibromyalgia (p < 0.001), anxiety–depression (p < 0.001), an almost daily headache baseline (>28 days/month) (p < 0.0001), and analgesic overuse (p < 0.0001). The response rate was unaffected by age and experience. After a multivariate logistic analysis, almost daily headaches (p < 0.001), a length of HF/CM > 6 years (p = 0.015), and anxiety–depression (p = 0.017) remained significant. Fremanezumab showed excellent tolerance. Conclusions: These real-life results confirm the efficacy of fremanezumab. The main factors associated with a lack of response were almost daily/daily headaches and a disease duration > 6 years. Half of the patients who failed to respond to erenumab improved on fremanezumab, making it sensible to switch to a treatment with a different mechanism of action, but trying a third anti-CGRP treatment in patients with no response to both a receptor-targeted and a ligand-targeted CGRP antibody hardly seems justifiable from our experience. [ABSTRACT FROM AUTHOR]

Background/objectives: Eating habits have been proposed as a potential therapeutic approach for migraines; nevertheless, scientific evidence to support firm recommendations is lacking. Specifically, dietary habits in migraineurs living in Spain have not been investigated. Therefore, this study aimed to evaluate their dietary patterns and examine how these habits vary based on the frequency of migraine attacks or the degree of migraine-related disability. Methods: An exploratory, observational, cross-sectional pilot study was conducted on 260 individuals (18–64 years old) diagnosed with migraine in Spain. Data on diet, lifestyle, and migraine characteristics were collected with an online questionnaire consisting of a food frequency questionnaire and enquires about perceptions about diet, lifestyle, and different aspects related to migraines. Statistical differences were analyzed with the Kruskal–Wallis test, followed by Dunn's post-hoc test, using JASP. Results: The consumption of plant-based foods was below the AESAN recommendations. No differences were observed in terms of food servings consumption across different migraine attack frequencies or levels of migraine-related disability. Both the chronic migraine group and the severe disability group showed differences in the consumption of some foods considered as migraine triggers (such as chocolate, cured cheese, cured meats, and alcoholic beverages). Moreover, people who suffered from infrequent migraine consumed significantly more caffeine than those who had chronic migraine. Conclusion: It remains unclear whether avoiding dietary migraine triggers is driven by the biological effects of certain food compounds or influenced by dietary perceptions and unfounded beliefs. Thus, further research on the role of diet in migraine management is necessary. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) is a highly disabling form of migraine in which patients have ≥ 15 headache days per month, of which at least 8 have the features of migraine. Galcanezumab is a monoclonal antibody to calcitonin gene-related peptide which is approved for the preventive treatment of migraine. Ability to convert patients from chronic migraine frequency to episodic migraine (EM) frequency is a clinically relevant and desirable outcome when prescribing preventive treatments to patients with CM. Methods: Patients aged 18–65 years with an ICHD-3β diagnosis of CM were randomized 2:1:1 to receive monthly injections of placebo (N = 558), galcanezumab 120 mg with a 240-mg loading dose (N = 278), or galcanezumab 240 mg (N = 277) during a 3-month double-blind period of the phase 3 REGAIN trial. Patients could subsequently enter a 9-month open-label extension in which they received galcanezumab 120 mg or 240 mg/month per investigator's discretion. In this post-hoc analysis, we assessed the percentages of patients who shifted to EM (< 8 migraine headache days or < 15 headache days/month), low frequency EM (LFEM; <8 migraine headache days/month), and very low frequency EM (VLFEM; <4 migraine headache days/month) for at least 3 consecutive months. Double-blind percentage comparisons versus placebo represent modeled estimates from raw rates. Results: At baseline, patients had a mean of 19.4 migraine headache days per month (SD = 4.5) and 21.4 headache days per month (SD = 4.1). During the 3-month double-blind treatment period, a greater percentage of galcanezumab-treated patients shifted to EM frequency and maintained it across all 3 months (31.5%) than did placebo-treated patients (19.8%, p < 0.001). Among galcanezumab-treated patients across the entire 12-month trial, 65.1% shifted from CM to EM frequency, with 44.2% shifting to LFEM and 21.5% shifting to VLFEM for ≥ 3 consecutive months. Proportions of patients shifting from CM to EM frequency for ≥ 3 consecutive months and until last patient visit were: 55.0% to EM; 33.4% to LFEM; 13.9% to VLFEM. Conclusion: These results suggest that galcanezumab helped a majority of patients convert from chronic to episodic migraine frequency over the course of this 12-month study. Trial registration: Clinicaltrials.gov NCT02614261, first registered November 25, 2015. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Published evidence supporting efficacy of calcitonin gene-related peptide receptor antagonists as acute migraine treatments in males is limited. Methods: 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). Results: 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. Conclusion/Interpretation: 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. Trial registration: ClinicalTrials.gov: NCT02828020; NCT02867709; NCT04492020; NCT01613248; NCT02848326; NCT03777059; NCT04740827; NCT03855137 [ABSTRACT FROM AUTHOR]

Background: The present study aimed to evaluate the risk and impact of fibromyalgia in relation to headache frequency in migraine patients. Methods: 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. Results: 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 (p < 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, p = 0.019) and ≥21 MHDs (14.5%) (OR = 3.68, 95% CI = 2.08–6.49, p < 0.001) were more likely to have fibromyalgia. Patients with more frequent headaches had higher FS and FIQR scores (all p < 0.001 between MHD categories). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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 that increased frequency of migraine promotes physiological changes including increased expression of TGV1 CGRP along with sensitization to CGRP-induced nociception in both males and females. Thus, as EM transforms to CM, CGRP-dependent mechanisms may become increasingly important, consistent with observations of efficacy of CGRP targeting therapies for migraine prevention in both men and women. Our results also suggest the possibility of enhanced efficacy of CGRP-receptor antagonists for the acute treatment of migraine in men as migraine frequency increases. [ABSTRACT FROM AUTHOR]

Exosomes have been identified as optimal biomarkers to screen for multiple diseases. However, few studies focus on the abundant exosome population isolated from plasma of migraine. This study investigated whether proteins in abundant exosomes can aid in the diagnosis of chronic migraine (CM). Plasma exosomes were collected by centrifugation, from which protein samples were extracted. A pilot study (CM, 18; episodic migraine (EM), 26) followed by a second dataset (CM, 26; EM, 16; tension-type headache (TTH), 20; control, 22) was applied to establish a diagnostic model of CM. We employed proteomics based on liquid chromatography-tandem mass spectrometry (LC–MS/MS) to search for potential candidate biomarkers in plasma exosomes from CM patients. In total, 530 proteins in plasma exosomes were co-detected. Among them, 13 proteins were found significantly dysregulated between the plasma exosomes of CM patients and other groups. The receiver operating characteristic curve analysis revealed a combination of six proteins (upregulated: RAP2B, AK1, BID, DAG1, PICALM, PSMB2) could distinguish CM patients with high accuracy. Linear correlation analysis showed that the combination was significantly correlated with Headache Impact Test (HIT-6) scores (assessing the negative impact of headaches on normal daily activity). The RT-qPCR results showed the same trends in CM models with nitroglycerin as the exosomal protein sequencing results. These data revealed dysregulated proteins in plasma exosomes of CM, and the combination of plasma exosomal proteins RAP2B, AK1, BID, DAG1, PICALM, and PSMB2 could serve as a novel candidate biomarker for CM diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To confirm a previously reported association of TRPV1 rs8065080 with the risk of transformation from episodic (EM) to chronic migraine (CM) and to extend knowledge about the role of other TRPV1 single nucleotide polymorphisms (SNPs), we first investigated the impact of three TRPV1 SNPs (rs8065080, rs222747 and rs222749) on the risk of migraine chronification in a case-control study. A systematic review and meta-analysis were then conducted to summarize the accumulated findings. Methods: Genotyping of the selected TRPV1 SNPs was performed using TaqMan real-time PCR in 167 EM and 182 CM participants. Crude and adjusted odds ratios with associated 95% confidence intervals were calculated in the log-additive, dominant, and recessive genetic models. A comprehensive literature search was performed in PubMed, Web of Knowledge, Cochrane Library, and OpenGrey until February 2024. Results: In our case-control study, no association was found between TRPV1 SNPs and the risk of migraine chronification, both in the unadjusted logistic regression models and after adjustment for confounding clinical variables. The results of the meta-analysis with a total of 241 participants with EM and 223 with CM confirmed no association between TRPV1 SNPs and the risk of migraine chronification in any of the genetic models tested. Conclusion: The results of the present case-control study and meta-analysis exclude a major role of TRPV1 rs8065080, rs222747, and rs222749 as risk factors for migraine chronification. However, further research is needed to investigate the gene-gene and gene-environment interactions of TRPV1 SNPs on the risk of transformation from episodic to chronic migraine. [ABSTRACT FROM AUTHOR]

Introduction: Longer periods between headache episodes (interictal periods) may provide greater time for the nervous system to reset from a previous episode, potentially improving disease status and health-related quality of life. This post hoc analysis evaluated this hypothesis by associating patients’ longest interictal periods with improvements in patient-reported outcomes. Methods: PROMISE-2 (NCT02974153) was a double-blind, placebo-controlled study evaluating eptinezumab for preventive treatment of chronic migraine (N = 1072). Daily electronic diary data from Weeks 1–12 and Weeks 1–24 were used to identify interictal periods, defined as days between headache episodes. For each patient, the longest interictal period within these intervals was identified and categorized (1–4, 5–9, 10–14, > 14, and > 21 days). For each category, the following patient-reported outcomes were assessed: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and patient-identified most bothersome symptom (PI-MBS). Results: Excluding interictal periods with > 10% missing data (resulting in 1010 patients with sufficient data), the mean (SD) of longest interictal periods over Weeks 1–12 was 9.4 (11.0) days. A ≥6-point HIT-6 reduction was observed in 78% (56/72) vs 26% (91/351) of patients with a > 21-day vs 1–4-day longest interictal period, respectively; much or very much improvement per PGIC was reported in 90% (65/72) vs 25% (87/348), respectively, and per PI-MBS was reported in 88% (63/72) vs 26% (92/348), respectively. Similar results were observed for Weeks 1–24. Conclusion: Longer interictal periods were associated with more patients indicating positive changes in headache-related life impact, disease status, and symptomology. Trial registration: ClinicalTrials.gov (identifier: NCT02974153; registered: 2016-11-23) [ABSTRACT FROM AUTHOR]

Background/Objectives: Medication-overuse headache (MOH) is a disabling condition affecting patients with chronic migraine resulting from excessive use of acute headache medication. It is characterized by both pain modulation and addiction-like mechanisms involving the brainstem raphe, a region critical to serotonergic signaling. This study investigates whether alterations in the brainstem raphe, assessed via transcranial sonography (TCS), are associated with MOH and independent of depressive symptoms, aiming to explore their utility as a biomarker. Methods: This prospective case-control study included 60 migraine patients (15 with MOH) and 7 healthy controls. Comprehensive clinical and psychometric assessments were performed to evaluate headache burden, medication use, and depressive symptoms. TCS was used to assess brainstem raphe echogenicity, with findings analyzed using generalized linear models adjusted for depression. Results: Non-visibility of the brainstem raphe was significantly associated with MOH, with an unadjusted odds ratio (OR) of 6.88 (95% CI: 1.32–36.01, p = 0.02). After adjusting for depressive symptoms, this association remained significant, with an adjusted OR of 1.85 (95% CI: 1.02–3.34, p = 0.041). TCS demonstrated good intraclass correlation, highlighting its reproducibility and ability to detect changes relevant to MOH pathophysiology. Conclusions: Brainstem raphe alterations are associated with MOH and may serve as a potential biomarker for its diagnosis and management. TCS offers a non-invasive, cost-effective tool for identifying MOH-specific mechanisms, which could improve clinical decision-making and support personalized care in chronic headache disorders. Further studies are needed to validate these findings and refine the clinical applications of brainstem-focused diagnostics. [ABSTRACT FROM AUTHOR]

Abstract The association between migraine and cognitive function has been studied during the last decade, however, this relationship is not well established. As migraine prevalence is highest between the ages of 30–40, aligning with some of our most productive years, we must understand cognitive changes within this disorder. Cognitive impairment potentially limits social and professional interactions, thus negatively impacting quality of life. Therefore, we will review the relationship between prevalent migraine and cognition. Cognitive dysfunction has been reported to be the second largest cause of disability, after pain, in migraine patients. While subjective patient reports on cognition consistently describe impairment, findings for objective neuropsychological assessments vary. Many studies report worse cognitive performance in the ictal phase compared to controls, which can persist into the postictal period, although whether this continues in the interictal period has been understudied. There is limited consensus as to whether cognition differs in migraine with aura versus migraine without aura, and while many studies do support cognitive impairment in chronic migraine, it remains uncertain as to whether this is more debilitating than the cognitive difficulties experienced by those with episodic migraine. To date, objective assessment of neurological abnormalities that may underlie cognitive impairment through neuroimaging has been underutilized. There is limited consensus as to whether cognitive impairment is a characteristic specific to migraine, whether it is driven by a combination of factors including co-morbidities such as anxiety, depression, or vascular dysfunction, treatment, or whether it is a more general characteristic of pain disorders. Overall, increasing numbers of studies support cognitive impairment in migraine patients. Future studies should consider longitudinal study designs to assess cognition across different migraine phases and subtypes of the disorder, including migraine with aura and chronic migraine, as well as controlling for important confounders such as treatment use.

Abstract Previous research has focused on the possibility of cervical dysfunction in migraine patients, similar to what is observed in patients with tension-type headaches. However, there is no evidence concerning the physical function of other body regions, even though lower levels of physical activity have been reported among migraine patients. The aim of this study was to compare cervical and extra-cervical range of motion, muscular strength, and endurance, as well as overall levels of physical activity, between patients with chronic migraine (CM) and asymptomatic participants. The secondary objective included the analysis of associations between CM-related disability and various physical and psychological variables. A total of 90 participants were included in this cross-sectional study: 30 asymptomatic participants (AG) and 60 patients with CM. Cervical and lumbar range of motion, strength and endurance, as well as handgrip strength were measured. Headache-related disability, kinesiophobia, pain behaviors, physical activity level and headache frequency were assessed through a self-report. Lower values were found in CM vs AG for cervical and lumbar ranges of motion (p

Background. Among patients with chronic migraine (CM), emotional disorders (anxiety, depression) are common, promoting the chronic course of migraine and making treatment challenging. Cognitive behavioral therapy (CBT) is promising in the complex treatment of patients with CM and emotional disorders. However, few randomized studies have been conducted to assess the effectiveness of CBT in this category of patients. Aim. To evaluate the effectiveness of an interdisciplinary program, including CBT, in the treatment of patients with CM and emotional disorders (anxiety, depression). Materials and methods. The study included 176 patients with CM and emotional disorders (55 males and 121 females), mean age 36.2 ±8.7 years. All patients underwent clinical interviews, neurological examinations, and testing using clinical and psychological techniques. Patients were randomized into two groups: Group 1 received the standard of care (preventive and acute treatment pharmacotherapy, lifestyle recommendations, physical activity during the day, detoxification therapy in the presence of drug-induced headache – HA) and CBT in the form of 10 individual face-to-face sessions aimed at treating pain, improving emotional state and daily activity; Group 2 received only the standard of care. All patients were evaluated for clinical and psychological parameters before treatment and at 3, 6, 12, and 24 months after the start of treatment. Results. After 3 months of treatment, a statistically significant (p0.05) improvement was observed in Group 1: a decrease in the HA frequency, the use frequency and daily doses of painkillers, points of the scale for assessing the effect of migraine on daily activity, the pain catastrophizing scale, the Spielberger-Khanin scale of personal and situational anxiety, the depression scale of the Center for Epidemiological Research. The improvements persisted after 6, 12, and 24 months from the start of treatment. After 3 months of treatment, Group 2 patients showed a statistically significant improvement in only four indicators at Month 3 of follow-up: the HA frequency, the use frequency and daily doses of painkillers, points of the scale for assessing the effect of migraine on daily activity. However, no improvements were observed after 6, 12, and 24 months of follow-up in Group 2. After 3 months of treatment, the clinical effect of CM (decrease in the HA frequency by 50% or more) in Group 1 was reported in 74% of patients vs 44% in Group 2, with a significant difference (p0.001). After 24 months of follow-up, 80% of patients in Group 1 had a clinical effect regarding CM, and 31% in Group 2. Conclusion. An interdisciplinary program that includes CBT is significantly more effective than the standard of care for CM and emotional disorders in the short and long term.

Abstract Background Chronic migraine (CM) is a serious neurological disorder. Central sensitization is one of the important pathophysiological mechanisms underlying CM, and microglia-induced neuroinflammation conduces to central sensitization. Triggering receptor expressed on myeloid cells 2 (TREM2) is presented solely in microglia residing within the central nervous system and plays a key role in neuroinflammation. Metformin has been shown to regulate inflammatory responses and exert analgesic effects, but its relationship with CM remains unclear. In the study, we investigated whether metformin modulates TREM2 to improve central sensitization of CM and clarified the potential molecular mechanisms. Methods A CM mouse model was induced by administration of nitroglycerin (NTG). Behavioral evaluations were conducted using von Frey filaments and hot plate experiments. Western blot and immunofluorescence techniques were employed to investigate the molecular mechanisms. Metformin and the SYK inhibitor R406 were administered to mice to assess their regulatory effects on neuroinflammation and central sensitization. To explore the role of TREM2-SYK in regulating neuroinflammation with metformin, a lentivirus encoding TREM2 was injected into the trigeminal nucleus caudalis (TNC). In vitro experiments were conducted to evaluate the regulation of TREM2-SYK by metformin, involving interventions with LPS, metformin, R406, siTREM2, and TREM2 plasmids. Results Metformin and R406 pretreatment can effectively improve hyperalgesia in CM mice. Both metformin and R406 significantly inhibit c-fos and CGRP expression in CM mice, effectively suppressing the activation of microglia and NLRP3 inflammasome induced by NTG. With the administration of NTG, TREM2 expression gradually increased in TNC microglia. Additionally, we observed that metformin significantly inhibits TREM2 and SYK expression in CM mice. Lv-TREM2 attenuated metformin-mediated anti-inflammatory responses. In vitro experiments, knockdown of TREM2 inhibited LPS-induced SYK pathway activation and alleviated inflammatory responses. After the sole overexpression of TREM2, the SYK signaling pathway is activated, resulting in the activation of the NLRP3 inflammasome and an increased expression of pro-inflammatory cytokines; nevertheless, this consequence can be reversed by R406. The overexpression of TREM2 attenuates the inhibition of SYK activity mediated by metformin, and this effect can be reversed by R406. Conclusions Our findings suggest that metformin attenuates central sensitization in CM by regulating the activation of microglia and NLRP3 inflammasome through the TREM2-SYK pathway. Graphical Abstract

Abstract Objective Chronic migraine (CM) patients with medication overuse headache (MOH) were recently shown to be associated with leaky gut and inflammation. We aimed to investigate gut microbiota profiles of CM patients with MOH, and their correlations with inflammatory serum parameters, migraine food triggers, and comorbid anxiety and depression. Materials and methods The study included women participants (32 CM patients with NSAID overuse headache, and 16 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, presence of irritable bowel syndrome symptoms, and HADS-D and HADS-A scores were recorded. Serum samples were collected to measure circulating LPS, HMGB1, HIF-1α, and IL-6. The gut microbiota profiles of the patients were evaluated using fecal samples. Results Serum LPS, HMGB1, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the healthy controls. HADS-A and HADS-D scores were considerably higher in the CM + MOH group compared to the healthy controls. In the microbiota analysis, alpha and beta diversities were similar between the two groups. The class Clostridia, the order Eubacteriales, and the genus Ruminococcus were less abundant in the CM + NSAID overuse headache group compared to the control group. At the genus level Desulfovibrio, Gemmiger, and Dialister and at the species level, Clostridium fessum, Blautia luti, Dorea longicatena, Eubacterium coprostanoligenes, and Gemmiger formicilis were more abundant in the CM + NSAID overuse headache group compared to the control group. Desulfovibrio, Gemmiger, Dialister, Ethanoligenens harbinense, Eubacterium coprostanoligenes, Dorea longicatena, and Thermoclostridium stercorarium showed positive correlations and Clostridia bacteria showed negative correlations with migraine food triggers. Positive correlations were found between LPS and Hapalosiphonaceae, HMGB1 and Melghirimyces, HIF1-α and Rouxeilla and Blautia luti, IL-6 and Melghirimyces and Ruminococcus. Conclusion In CM patients with MOH, we have revealed the presence of dysbiosis towards an inflammatory state, and positive correlations were shown between altered gut microbiota and inflammatory serum parameters and migraine food triggers.

Abstract Background The International Classification of Headache Disorders (ICHD-3) uses moderate or severe pain intensity in the diagnostic criterion for migraine. However, few studies have analyzed pain rating on a visual analog scale to identify the numerical intensity that correlates with migraine. Objective To evaluate the impact of daily self-rated headache pain among patients with either episodic or chronic migraine. This study specifically aims to evaluate the probability of patients labeling their head pain as a headache vs. migraine based on the pain level reported. Methods A retrospective chart review was conducted on patients with a clinical diagnosis of migraine from July 1, 2014, to July 1, 2019. Results Data of 114 subjects (57 episodic migraine and 57 chronic migraine) were used for analysis. Patients with episodic migraine on average rated a migraine more severe than a headache (4.1 vs. 6.4; p

Previous research has focused on the possibility of cervical dysfunction in migraine patients, similar to what is observed in patients with tension-type headaches. However, there is no evidence concerning the physical function of other body regions, even though lower levels of physical activity have been reported among migraine patients. The aim of this study was to compare cervical and extra-cervical range of motion, muscular strength, and endurance, as well as overall levels of physical activity, between patients with chronic migraine (CM) and asymptomatic participants. The secondary objective included the analysis of associations between CM-related disability and various physical and psychological variables. A total of 90 participants were included in this cross-sectional study: 30 asymptomatic participants (AG) and 60 patients with CM. Cervical and lumbar range of motion, strength and endurance, as well as handgrip strength were measured. Headache-related disability, kinesiophobia, pain behaviors, physical activity level and headache frequency were assessed through a self-report. Lower values were found in CM vs AG for cervical and lumbar ranges of motion (p < 0.05; effect sizes ranging from 0.57 to 1.44). Also, for neck extension strength (p = 0.013; d = − 0.66), lumbar strength (p < 0.001; d = − 1.91) and handgrip strength (p < 0.001; d = − 0.98), neck endurance (p < 0.001; d = − 1.81) and lumbar endurance (p < 0.001; d = − 2.11). Significant differences were found for physical activity levels (p = 0.01; d = − 0.85) and kinesiophobia (p < 0.001; d = − 0.93) between CM and AG. Headache-related disability was strongly associated with headache frequency, activity avoidance, and rest, which together explained 41% of the variance. The main findings of this study suggest that patients with CM have a generalized fitness deficit and not specifically cervical dysfunction. These findings support the hypothesis that migraine patients have not only neck-related issues but also general body conditions. [ABSTRACT FROM AUTHOR]

The association between migraine and cognitive function has been studied during the last decade, however, this relationship is not well established. As migraine prevalence is highest between the ages of 30–40, aligning with some of our most productive years, we must understand cognitive changes within this disorder. Cognitive impairment potentially limits social and professional interactions, thus negatively impacting quality of life. Therefore, we will review the relationship between prevalent migraine and cognition. Cognitive dysfunction has been reported to be the second largest cause of disability, after pain, in migraine patients. While subjective patient reports on cognition consistently describe impairment, findings for objective neuropsychological assessments vary. Many studies report worse cognitive performance in the ictal phase compared to controls, which can persist into the postictal period, although whether this continues in the interictal period has been understudied. There is limited consensus as to whether cognition differs in migraine with aura versus migraine without aura, and while many studies do support cognitive impairment in chronic migraine, it remains uncertain as to whether this is more debilitating than the cognitive difficulties experienced by those with episodic migraine. To date, objective assessment of neurological abnormalities that may underlie cognitive impairment through neuroimaging has been underutilized. There is limited consensus as to whether cognitive impairment is a characteristic specific to migraine, whether it is driven by a combination of factors including co-morbidities such as anxiety, depression, or vascular dysfunction, treatment, or whether it is a more general characteristic of pain disorders. Overall, increasing numbers of studies support cognitive impairment in migraine patients. Future studies should consider longitudinal study designs to assess cognition across different migraine phases and subtypes of the disorder, including migraine with aura and chronic migraine, as well as controlling for important confounders such as treatment use. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the specific manifestations and differences in brain network activity and functional connectivity between brain networks in patients with trigeminal neuralgia and migraine, aiming to reveal the neural basis of these two diseases. Background: Head and facial pain, including trigeminal neuralgia and migraine, is prevalent globally. However, the underlying neural mechanisms of these conditions remain unclear. Resting-state functional connectivity studies based on independent component analysis (ICA) may offer new insights into these diseases. Methods: The study involved 23 chronic migraine, 37 episodic migraine, 21 trigeminal neuralgia patients, and 33 age- and gender-matched controls. Resting-state functional magnetic resonance imaging was performed, and five sets of brain network components were extracted through ICA. Neuronal activity indicators were calculated for each participant's independent components, including amplitudes of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo). Functional connectivity was also assessed and compared among the four groups. Results: Trigeminal neuralgia patients showed reduced ALFF in the dorsal attention network versus episodic migraine patients and controls. Both trigeminal neuralgia and chronic migraine patients had decreased ReHo in this network. Migraine patients had weaker connectivity between the default mode and visual networks than controls. Trigeminal neuralgia patients also showed higher connectivity between the somatosensory motor and dorsal attention networks. Compared to episodic migraine, trigeminal neuralgia, and chronic migraine patients had increased connectivity between the visual and dorsal attention networks. Conclusion: The study provides evidence that long-term chronic head and facial pain may contribute to abnormalities in the activation and connectivity of the dorsal attention network. Compared to migraine patients, trigeminal neuralgia patients exhibit abnormal brain network connectivity, particularly within the somatomotor network, which may explain the presence of significant "trigger points." These findings offer new perspectives for understanding the characteristics of different head and facial pain subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody). Methods: This is a cross-sectional, self-reported, online survey of subjects in Lilly's Emgality® Patient Support Program in 2022. Questionnaires collected insights into subjects' prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs. Results: Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2 years (± 11.9) at diagnosis and 40.6 (± 12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (± 4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects. Conclusion: People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey. Graphical abstract available for this article. [ABSTRACT FROM AUTHOR]

Introduction: Combination use of atogepant and onabotulinumtoxinA has the potential to be more effective than either alone for the preventive treatment of chronic migraine (CM) due to their complementary mechanisms of action. This analysis collected real-world data to evaluate the safety, tolerability, and effectiveness of adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM. Methods: This retrospective, longitudinal, multicenter chart review included adults with CM who received ≥ 2 consecutive cycles of onabotulinumtoxinA before ≥ 1 month of onabotulinumtoxinA and atogepant combination treatment. Charts at atogepant prescription (index date) and two subsequent onabotulinumtoxinA treatment visits (~ 3 and ~ 6 months post-index) were reviewed for change from baseline in monthly headache days (MHDs), ≥ 50% reduction in MHDs, discontinuation rates, and adverse events (AEs). Results: Of the 55 charts that met safety analysis criteria, 31 had data on headache days at index and first post-index visit and were eligible for effectiveness analysis (mean age 46.7 years, 94.5% female). For those with data available prior to onabotulinumtoxinA treatment (n = 25), the mean MHD was 24.0 days, reduced by 8.15 days after onabotulinumtoxinA treatment. After atogepant was added, MHD was incrementally reduced by 4.53 days and 8.75 days from index date to the first (N = 31) and second (N = 23) post-index onabotulinumtoxinA treatment visit, respectively. A ≥ 50% reduction in MHDs was achieved by 45.2% of patients ~ 3 months post-index. Atogepant and onabotulinumtoxinA were discontinued by 16.1% and 6.5% of patients, respectively. In the safety population, 32.7% of patients experienced ≥ 1 AE. No serious AEs were reported. Conclusions: This real-world study of patients with CM demonstrated that adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM was effective by providing an additional reduction in MHDs over ~ 3 and ~ 6 months of combination treatment. Safety results were consistent with the known safety profiles of onabotulinumtoxinA and atogepant, with no new safety signals identified. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to demonstrate the change in pain intensity, frequency of attacks, and life quality before and after treatment in patients with chronic migraine who underwent greater occipital nerve (GON) pulsed radiofrequency (PRF). Patients and methods: This prospective, cross-sectional study was conducted with 30 patients (1 male, 29 females; mean age: 43.7±9.8 years; range, 26 to 64 years) with chronic migraine diagnosed according to the beta version of the third edition of the International Classification of Headache Disorders. Patients who did not respond to conventional treatments were enrolled in the study. The PRF procedure on the proximal GON at the C2 vertebra level was performed under the guidance of ultrasound at 5 Hz and 5 msec pulsed width for 360 sec at 45 V. The Visual Analog Scale (VAS), pain frequency (per week), analgesic consumption frequency (per week), and the SF-12 (12-item Short-Form Health Survey) were used to compare pain intensity and quality of life (QoL) before and three months after treatment. Results: There was significant decrease in pain frequency (5.5 to 2.0), analgesic consumption frequency (7.0 to 2.0), and VAS scores (9.0 to 7.0) three months after the intervention compared to baseline (p<0.001). At the end of the first month, 17 patients reported more than 50% reduction in pain. In this study, a prominent improvement was observed in mental and physical components of QoL scores, indicating that disability rates of chronic migraine patients decreased with PRF compared to pretreatment. Conclusion: According to the results, PRF can be considered an effective treatment option in patients with refractory chronic migraine. [ABSTRACT FROM AUTHOR]

Background: Migraine is a debilitating neurological condition linked to various psychological comorbidities. The aims of our study are: 1) to evaluate potential psychopathological differences between patients in treatment with anti-CGRP monoclonal antibodies (SPECIFIC group) and those with onabotulinumtoxin-A/oral pharmacotherapy (Group NON-SPECIFIC), 2) to compare treatment efficacy over time between groups, and examined whether psychopathological comorbidities can influence it. Methods: This is a post-hoc ambispective study: a retrospective analysis of patient-level real-life data prospectively collected for clinical evaluation. We enrolled 102 patients with chronic migraine (CM), 64 in treatment with erenumab or galcanezumab, and 38 with botulinum toxin or oral pharmacotherapies. Psychopathological variables are assessed at baseline, whereas clinical factors over time. Results: The NON-SPECIFIC group showed more pronounced emotion regulation difficulties (DERS, p = 0.001), alexithymia (TAS-20, p = 0.012), and impulsiveness (BIS-11, p = 0.002) with respect to the SPECIFIC group. Moreover, treatment efficacy overtime was more pronounced in the group with anti-CGRP treatment with a reduction of migraine frequency overtime, pain intensity, and improved quality of life up to six months post-treatment. Psychopathological comorbidity did not influence treatment efficacy. Conclusions: Our study highlighted more pronounced psychopathological comorbidities in patients in treatment with NON-SPECIFIC therapies in terms of impulsivity, alexithymia, and emotion regulation. Moreover, treatment efficacy overtime was more pronounced and stable over time in the SPECIFIC group, and psychopathological comorbidity did not influence it. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic migraine with medication-overuse headache (CM-MOH) is neurophysiologically characterized by increased cortical excitability with sensitization at both the thalamocortical and the cortical levels. It is unclear whether the increased cortical excitability could be reverted by medication withdrawal (i.e., brain state) or whether it is a brain trait of individuals predisposed to medication overuse. In this study, we aim to investigate whether withdrawal from overused drugs can influence and restore these neurophysiological abnormalities. Methods: Somatosensory evoked potentials (SSEPs) were elicited by electrical stimulation of the median nerve (M), the ulnar nerve (U), and the simultaneous stimulation of both nerves (MU) in 14 patients with CM-MOH before (T0) and after (T1) a three-week withdrawal protocol and, for comparison, in 14 healthy volunteers (HVs) of a comparable age distribution. We measured the level of thalamocortical (pre-HFO) and cortical activation (post-HFO) by analyzing the high-frequency oscillations (HFOs) embedded in parietal N20 median SSEPs. Furthermore, we calculated the habituation and the degree of cortical lateral inhibition (dLI) of N20-P25 low-frequency SSEPs. Results: After the three-week withdrawal protocol (T1), we observed a normalization of the baseline habituation deficit (T0: +0.10 ± 0.54; T1: −0.53 ± 0.8; p = 0.040) and a reduction in the amplitude for both pre-HFO (p < 0.009) and post-HFO (p = 0.042), with values comparable to those of the HVs. However, no effects were observed on the dLI (p = 0.141). Conclusions: Our findings showed that withdrawal from overused drugs could affect the increased excitability of the non-painful somatosensory system in patients with CM-MOH, reducing the level of sensitization at both the thalamocortical and the cortical levels. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) is a serious neurological disorder. Central sensitization is one of the important pathophysiological mechanisms underlying CM, and microglia-induced neuroinflammation conduces to central sensitization. Triggering receptor expressed on myeloid cells 2 (TREM2) is presented solely in microglia residing within the central nervous system and plays a key role in neuroinflammation. Metformin has been shown to regulate inflammatory responses and exert analgesic effects, but its relationship with CM remains unclear. In the study, we investigated whether metformin modulates TREM2 to improve central sensitization of CM and clarified the potential molecular mechanisms. Methods: A CM mouse model was induced by administration of nitroglycerin (NTG). Behavioral evaluations were conducted using von Frey filaments and hot plate experiments. Western blot and immunofluorescence techniques were employed to investigate the molecular mechanisms. Metformin and the SYK inhibitor R406 were administered to mice to assess their regulatory effects on neuroinflammation and central sensitization. To explore the role of TREM2-SYK in regulating neuroinflammation with metformin, a lentivirus encoding TREM2 was injected into the trigeminal nucleus caudalis (TNC). In vitro experiments were conducted to evaluate the regulation of TREM2-SYK by metformin, involving interventions with LPS, metformin, R406, siTREM2, and TREM2 plasmids. Results: Metformin and R406 pretreatment can effectively improve hyperalgesia in CM mice. Both metformin and R406 significantly inhibit c-fos and CGRP expression in CM mice, effectively suppressing the activation of microglia and NLRP3 inflammasome induced by NTG. With the administration of NTG, TREM2 expression gradually increased in TNC microglia. Additionally, we observed that metformin significantly inhibits TREM2 and SYK expression in CM mice. Lv-TREM2 attenuated metformin-mediated anti-inflammatory responses. In vitro experiments, knockdown of TREM2 inhibited LPS-induced SYK pathway activation and alleviated inflammatory responses. After the sole overexpression of TREM2, the SYK signaling pathway is activated, resulting in the activation of the NLRP3 inflammasome and an increased expression of pro-inflammatory cytokines; nevertheless, this consequence can be reversed by R406. The overexpression of TREM2 attenuates the inhibition of SYK activity mediated by metformin, and this effect can be reversed by R406. Conclusions: Our findings suggest that metformin attenuates central sensitization in CM by regulating the activation of microglia and NLRP3 inflammasome through the TREM2-SYK pathway. [ABSTRACT FROM AUTHOR]

To systematically examine the literature on the clinical consequences of inadvertent delays in scheduled onabotulinumtoxin A (OTA) therapy for chronic migraine during the COVID-19 pandemic and assess recommendations when access to OTA is limited. Background: The coronavirus (COVID-19) pandemic was unprecedented in its impact on the global medical community. Most healthcare institutions in the United States (US) and the world had begun significantly limiting elective procedures, undermining management of many debilitating chronic conditions. OTA injections, were similarly involuntarily postponed, leading to significant setbacks in symptom control. Methods: A comprehensive literature search was conducted on databases of Medline and Embase with search timeframe defined as the point of database inception to March 1st, 2024, and the search was performed on March 2nd, 2024. The search strategy was independently formulated by two authors (QR and CR) and was reviewed and approved by all authors of the article after appropriate amendments. Results: A total of nine articles met the defined inclusion criteria. They collectively demonstrated marked delays in OTA treatment with decline in migraine symptom control measured in the form of migraine intensity, frequency, as well as patient satisfaction in disease management. Quality of care in the form of follow-ups also appeared compromised. Alternative strategies of telemedicine and the administration of calcitonin gene-related peptide monoclonal antibodies (CGRP mAb) were adopted in place of conventional treatment. Conclusion: The COVID-19 pandemic had caused marked clinical deterioration in the migraine patient populations across US, Europe, and the Middle East. Strategies employed to circumvent this limitation included the adoption of remote consultation via telemedicine as well as the use of pharmacological agents such as CGRP antagonists. In the event of a reoccurrence of a worldwide pandemic, strategies should be implemented to prevent the cessation of needed treatment for those suffering from chronic migraine. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic migraine (CM) is a neurological disorder that causes significant disability, loss of productivity, and economic burden. Preventive treatments, including pharmacological and educational interventions, are crucial for managing CM effectively. The aim of this study was to analyze whether adding a therapeutic telehealth education program (TTEP) to pharmacological treatment achieved a greater reduction in the number of headache days experienced by patients with CM. Methods: A randomized, double-blind, controlled pilot study with two parallel groups was performed. Patients with a diagnosis of CM and who were being treated with Botulinum Toxin were randomly assigned to either the EG (therapeutic education program about the neuroscience of pain, migraine, pain strategies, sleep habits, exercise, nutrition, postural habits, and relaxation strategies) or CG (general health recommendations with no specific content about migraine). The intervention lasted a total of eight weeks and was delivered via a telehealth application (APP). Headache frequency, migraine frequency, pain intensity, headache impact, allodynia, fear of movement, pain catastrophizing, chronic pain self-efficacy, anxiety and depression, sleep quality, and sedentary lifestyle were measured at baseline (M0), one month after the intervention started (M1), at the end of the intervention (M2), and one month after the intervention was completed for follow-up (M3). Results: In total, 48 patients participated. There were differences between the groups in the following outcomes in favor of EG for headache frequency at the one-month follow-up (p = 0.03; d = 0.681); chronic pain self-efficacy at post-treatment (p = 0.007; d = 0.885) and at the one-month follow-up (p < 0.001; d = 0.998); and sleep quality at post-treatment (p = 0.013; d = 0.786) and at the one-month follow-up (p < 0.001; d = 1.086). No differences existed between the groups for the other outcomes examined (p < 0.05). Conclusions: The use of TTEP reduced the number of headache days, improved sleep quality, and increased self-efficacy in managing pain. This pilot study suggests that the addition of a specialized TTPE to pharmacological treatments may be more effective than a general health recommendation program for migraine. [ABSTRACT FROM AUTHOR]

Objective: Chronic migraine (CM) patients with medication overuse headache (MOH) were recently shown to be associated with leaky gut and inflammation. We aimed to investigate gut microbiota profiles of CM patients with MOH, and their correlations with inflammatory serum parameters, migraine food triggers, and comorbid anxiety and depression. Materials and methods: The study included women participants (32 CM patients with NSAID overuse headache, and 16 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, presence of irritable bowel syndrome symptoms, and HADS-D and HADS-A scores were recorded. Serum samples were collected to measure circulating LPS, HMGB1, HIF-1α, and IL-6. The gut microbiota profiles of the patients were evaluated using fecal samples. Results: Serum LPS, HMGB1, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the healthy controls. HADS-A and HADS-D scores were considerably higher in the CM + MOH group compared to the healthy controls. In the microbiota analysis, alpha and beta diversities were similar between the two groups. The class Clostridia, the order Eubacteriales, and the genus Ruminococcus were less abundant in the CM + NSAID overuse headache group compared to the control group. At the genus level Desulfovibrio, Gemmiger, and Dialister and at the species level, Clostridium fessum, Blautia luti, Dorea longicatena, Eubacterium coprostanoligenes, and Gemmiger formicilis were more abundant in the CM + NSAID overuse headache group compared to the control group. Desulfovibrio, Gemmiger, Dialister, Ethanoligenens harbinense, Eubacterium coprostanoligenes, Dorea longicatena, and Thermoclostridium stercorarium showed positive correlations and Clostridia bacteria showed negative correlations with migraine food triggers. Positive correlations were found between LPS and Hapalosiphonaceae, HMGB1 and Melghirimyces, HIF1-α and Rouxeilla and Blautia luti, IL-6 and Melghirimyces and Ruminococcus. Conclusion: In CM patients with MOH, we have revealed the presence of dysbiosis towards an inflammatory state, and positive correlations were shown between altered gut microbiota and inflammatory serum parameters and migraine food triggers. [ABSTRACT FROM AUTHOR]

Objective: To qualitatively and quantitatively summarize the evidence for the use of onabotulinumtoxinA injections in children and adolescents with migraine. Background: There are limited evidence‐based treatment options for youth with migraine, especially youth with chronic migraine (CM). OnabotulinumtoxinA injections are an established evidence‐based treatment for adults with CM. While several studies have assessed their safety and efficacy among adolescents with CM, there are no published systematic reviews summarizing the pediatric evidence. Methods: We carried out a systematic review, reported according to the Preferred Reporting Items for Systematic Review and Meta‐Analysis, aiming to identify studies that included five or more children and adolescents aged ≤18 years with a diagnosis of migraine, who were treated with ≥50 units (U) of onabotulinumtoxinA and had outcomes assessed ≥4 weeks after one or more injection cycle. Both observational studies and randomized controlled trials (RCTs) were eligible for inclusion. Two investigators independently carried out the first (titles and abstracts) and second (full text) screening stages, as well as data extraction and quality appraisal. The American Academy of Neurology risk of bias grading scheme was used to assess study risk of bias. Studies with adequate data were pooled using random effects meta‐analyses, and Hedge's g standardized mean differences with 95% confidence intervals (CIs) were generated to estimate the effect sizes of the continuous outcomes included. Studies lacking data required for meta‐analysis were summarized qualitatively. Results: We screened 634 studies and included 14 studies comprising 491 participants, of whom 489 had CM. Two studies were RCTs, 12 were observational uncontrolled studies, and all but one study included only youth with CM. Five Class IV observational uncontrolled studies were amenable to pooling in meta‐analyses. After a mean of 2–2.6 injection cycles, headache frequency was shown to decrease significantly after treatment with onabotulinumtoxinA (Hedge's g = 0.97, 95% CI 0.58–1.35; p < 0.0001), as did severity (Hedge's g = 1.24, 95% CI 0.55–1.94; p = 0.0005), with both estimates having a large effect size magnitude. A Class I parallel‐group RCT of one injection series (155 U, 74 U, or placebo), powered to detect a change in 4 headache days per month, did not find outcome differences between the active and placebo treatment arms. A Class IV crossover RCT showed superiority of active (155 U) versus placebo injections. The remaining Class IV observational studies that were excluded from the meta‐analyses all showed improved outcomes with onabotulinumtoxinA injections over time. No serious adverse events related to treatment occurred. Conclusion: OnabotulinumtoxinA injections have established safety for use in children and adolescents with CM and are likely effective in reducing headache frequency and severity over time. However, in the absence of an adequately powered parallel‐group RCT assessing the efficacy of multiple injection cycles, it remains unclear if this intervention is superior to placebo. Plain Language Summary: The results of our review suggest that onabotulinumtoxinA injections are safe and that they are likely effective for children and adolescents with chronic migraine. However, the available research is generally biased because of study design issues, and it is still uncertain if onabotulinumtoxinA injections have benefits above and beyond the benefits of placebo injections for children and adolescents. Better‐designed research is required to understand if onabotulinumtoxinA injections are more effective than placebo injections in treating children and adolescents with chronic migraine. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of fremanezumab for migraine prevention. Design Retrospective, single-center, real-world study. Setting Regional tertiary headache center in Japan. Subjects Adult individuals with migraine (n = 165, male = 17, female = 148; average age = 45.5 ± 16.0 years) who received fremanezumab between September 2021 and August 2022. Methods Fremanezumab was administered subcutaneously at a monthly dose of 225 mg or quarterly dose of 675 mg based on patient preferences. Patients received fremanezumab treatment for up to 1 year unless it was discontinued. Monthly data were collected on migraine days, headache days, and days requiring acute medication. Results Of the 165 patients, 125 (75.7%) received fremanezumab as their first anti-calcitonin gene-related peptide-related antibody drug. Significant reductions in monthly migraine days, headache days, and days requiring acute medication were observed in those with episodic and chronic migraines. The baseline monthly headache days was 8.1 ± 4.0 in the episodic migraine group, which reduced to 6.1 ± 4.8, 5.8 ± 4.4, 4.7 ± 3.6, and 4.6 ± 3.3 days at 1, 3, 6, and 12 months, respectively; in the chronic migraine group, the baseline monthly headache days was 20.9 ± 6.1, which reduced to 17.0 ± 8.9, 15.0 ± 9.2, 13.0 ± 7.7, and 12.0 ± 9.1 days at 1, 3, 6, and 12 months, respectively. Treatment benefits were enhanced after 6 months of administering fremanezumab in the chronic migraine group. Conclusions In this real-world study of patients with migraine, fremanezumab appears to be effective and safe. Further studies are required to identify additional predictors of treatment success and failure with fremanezumab. [ABSTRACT FROM AUTHOR]

Introduction: Overuse of analgesics can lead to medication-overuse headache (MOH) in chronic migraine (CM) patients, and is often linked to addiction. This study explores the addiction-related characteristics and somatic amplification in patients with, CM with medication overuse headache (CM+MOH), CM, and healthy controls. Methods: 73 CM patients and 70 CM+MOH, along with 63 healthy controls, participated in the study. Assessments included a Sociodemographic Form, Migraine Disability Assessment Scale (MIDAS), Addiction Profile Index (API), Addiction Profile Index-Clinical Version (API-C), and the Somatosensory Amplification Scale (SSAS). Results: Substance use characteristics, craving, motivation for use, and addiction severity scores were higher in the CM+MOH group than in both the CM and the control group. Specifically, the SSAS scores within the CM+MOH group surpassed those of both the CM and control groups. In the CM+MOH group, SSAS scores were a strong predictor of the amount of analgesic usage. Besides, craving and motivation for substance use scores significantly predicted the number of days analgesic taken per month in the CM+MOH group Conclusion: CM patients with MOH exhibit a pronounced association with addiction, and a heightened manifestation of somatic symptoms. Addressing addiction characteristics and psychosomatic amplification is important to ensure comprehensive management. [ABSTRACT FROM AUTHOR]

Objective: Chronic migraine encephalalgia (CME) with concomitant temporomandibular disorder (TMD) is a serious illness with limited effective treatment options. This study explores the effectiveness of onabotulinumtoxinA (BtxA) as an adjunct therapeutic to TMJ arthroscopy in the relief of CME. Methods: A retrospective cohort study of patients receiving TMJ arthroscopy, with or without BtxA injections for CME, was conducted. Variables assessed include pain using a visual analog scale (VAS), maximal incisal opening (MIO), muscle soreness, and headache frequency and duration. Results: Sixty patients (44 BtxA, 16 Control), consisting of 56 (93.3%) females, met inclusion criteria. A significant reduction in pain is reported with patients receiving BtxA (p < 0.0001) on VAS as compared to Control group. BtxA treatment also significantly reduced headache frequency and duration (p < 0.05). Conclusion: These results support the use of adjunctive BtxA treatment with arthroscopy for the treatment of CME in the context of TMD. [ABSTRACT FROM AUTHOR]

Purpose of Review: Chronic migraine is a disabling progressive disorder without effective management approaches. Animal models have been developed and used in chronic migraine research. However, there are several problems with existing models. Therefore, we aimed to summarize and analyze existing animal models to facilitate translation from basic to clinical. Recent Findings: The most commonly used models are the inflammatory soup induction model and the nitric oxide donor induction model. In addition, KATP openers have also been used in model induction. Based on the above models, some molecular targets have been identified, such as glutamate receptors. However, each model has its shortcomings and characteristics, and there are still some common problems that need to be solved, such as spontaneous headache, evaluation criteria after model establishment, and identification methods. Summary: In this review, we summarized and highlighted the advantages and limitations of the currently commonly used animal models of chronic migraine with a special focus on drug discovery and current therapeutic strategies, and discussed the directions that can be worked on in the future. [ABSTRACT FROM AUTHOR]

Background: The International Classification of Headache Disorders (ICHD-3) uses moderate or severe pain intensity in the diagnostic criterion for migraine. However, few studies have analyzed pain rating on a visual analog scale to identify the numerical intensity that correlates with migraine. Objective: To evaluate the impact of daily self-rated headache pain among patients with either episodic or chronic migraine. This study specifically aims to evaluate the probability of patients labeling their head pain as a headache vs. migraine based on the pain level reported. Methods: A retrospective chart review was conducted on patients with a clinical diagnosis of migraine from July 1, 2014, to July 1, 2019. Results: Data of 114 subjects (57 episodic migraine and 57 chronic migraine) were used for analysis. Patients with episodic migraine on average rated a migraine more severe than a headache (4.1 vs. 6.4; p < 0.001). Patients with chronic migraine on average also rated migraine more severe than a headache (4.3 vs. 6.8; p = 0.0054). Chronic migraine patients transitioned from calling head pain a headache to a migraine significantly later than episodic migraine patients (4.5 vs. 6.8; p < 0.05). Conclusion: A migraine is perceived as having higher pain intensity than a headache in patients with both episodic and chronic migraine. On average, patients with chronic migraine had a higher pain rating at which they report head pain to be considered a migraine. [ABSTRACT FROM AUTHOR]

Background/Objectives: Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods: We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analysing the amplitude of the first block (100 sweeps) and to evaluate habituation by measuring the amplitude response decrement after six blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results: There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEP parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication withdrawal. Conclusions: We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine is a severe and common neurological disorder, yet its precise physiological mechanisms remain unclear. The IGF1/IGF1r signaling pathway plays a crucial role in pain modulation. Studies have shown that IGF1, by binding to its receptor IGF1r, activates a series of downstream signaling cascades involved in neuronal survival, proliferation, autophagy and functional regulation. The activation of these pathways can influence nociceptive transmission. Furthermore, alterations in IGF1/IGF1r signaling are closely associated with the development of various chronic pain conditions. Therefore, understanding the specific mechanisms by which this pathway contributes to pain is of significant importance for the development of novel pain treatment strategies. In this study, we investigated the role of IGF1/IGF1r and its potential mechanisms in a mouse model of chronic migraine. Methods: Chronic migraine was induced in mice by repeated intraperitoneal injections of nitroglycerin. Mechanical and thermal hypersensitivity responses were assessed using Von Frey filaments and radiant heat, respectively. To determine the role of IGF1/IGF1r in chronic migraine (CM), we examined the effects of the IGF1 receptor antagonist ppp (Picropodophyllin) on pain behaviors and the expression of calcitonin gene-related peptide (CGRP) and c-Fos. Result: In the nitroglycerin-induced chronic migraine model in mice, neuronal secretion of IGF1 is elevated within the trigeminal nucleus caudalis (TNC). Increased phosphorylation of the IGF1 receptor occurs, predominantly co-localizing with neurons. Treatment with ppp alleviated basal mechanical hypersensitivity and acute mechanical allodynia. Furthermore, ppp ameliorated autophagic dysfunction and reduced the expression of CGRP and c-Fos. Conclusion: Our findings demonstrate that in the chronic migraine (CM) model in mice, there is a significant increase in IGF1 expression in the TNC region. This upregulation of IGF1 leads to enhanced phosphorylation of IGF1 receptors on neurons. Targeting and inhibiting this signaling pathway may offer potential preventive strategies for mitigating the progression of chronic migraine. [ABSTRACT FROM AUTHOR]

OnabotulinumtoxinA (onabotA) is approved in the US for 12 therapeutic indications. Real-world data on onabotA multi-indication use are limited, often leading to delayed or reduced treatment. This study provides real-world evidence on the safety of onabotA when treating multiple indications concomitantly. SYNCHRONIZE was a multicenter, retrospective, chart-review study evaluating onabotA's safety for adults treated for ≥2 therapeutic indications within a 3-month period. The primary outcome was treatment-emergent adverse events (TEAEs) within 6 months post-treatment. A total of 279 patients were included. The most common concomitant indications treated were cervical dystonia and chronic migraine (43.4%). The average 3-month cumulative dose for multiple indications was 282.2 U. The treatment interval for multiple indications was ≤24 h for most patients (62.4%). Overall, 28.7% of patients reported ≥1 TEAE with no apparent trends in TEAEs and dose interval or cumulative dose. Reported TEAEs included UTI (5.7%), neck pain (5.0%), and headache (4.3%). No patient had a lack of effect according to clinical objective measurements. SYNCHRONIZE described the real-world safety of onabotA for patients treated concomitantly for ≥2 indications within a 3-month period. TEAEs were generally consistent with the known safety profiles of individual indications. No new safety signals were identified). [ABSTRACT FROM AUTHOR]

Chronic migraines have been described chiefly only from a clinical perspective. However, searching for reliable molecular markers has allowed for the discovery of the expression of different genes mainly associated with inflammation, neuro-vascularization, and pain-related pathways. The interest in microRNAs (miRs) that can regulate the expression of these genes has gained significant relevance since multiple miRs could play a key role in regulating these events. In this study, miRs were searched in samples from patients with chronic migraine, and the inclusion criteria were carefully reviewed. Different bioinformatic tools, such as miRbase, targetscan, miRPath, tissue atlas, and miR2Disease, were used to analyze the samples. Our findings revealed that some of the miRs were expressed more (miR-197, miR-101, miR-92a, miR-375, and miR-146b) and less (miR-133a/b, miR-134, miR-195, and miR-340) than others. We concluded that, during chronic migraine, common pathways, such as inflammation, vascularization, neurodevelopment, nociceptive pain, and pharmacological resistance, were associated with this disease. [ABSTRACT FROM AUTHOR]