Migraine Pain Research Articles

Magnetoencephalography studies in migraine and headache disorders: A systematic review.

Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long-term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression-a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers. To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings. We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer-reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected. We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting-state, while others investigated a sensory modality using an evoked or event-related paradigm with a total of 35 cohort and 3 case studies. Thirty-two studies focused exclusively on migraine, while the rest reported other primary headache disorders. The findings show an evolution of MEG from a 7- to a 306-channel system and analysis evolving from sensor-level evoked responses to more advanced source-level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case-control studies, which could have led to false-positive findings. More studies are needed to investigate the affective-cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders.

Comparative bioavailability of single-dose zavegepant during and between migraine attacks: A phase 1, randomized, open-label, fixed-sequence, two-period study.

To compare the rate and extent of absorption of zavegepant 10 mg (therapeutic dose) or 20 mg (supratherapeutic dose) nasal spray during a migraine attack versus non-migraine period, assess safety, and explore efficacy and the relationship between zavegepant concentration and therapeutic response. Physiologic changes occurring during a migraine attack could affect the pharmacokinetics of treatments for migraine. This was a Phase 1, multicenter, open-label, randomized, single-dose, two-period, fixed-sequence, comparative bioavailability study. Participants with a history of 2-8 migraine attacks per month of moderate or severe pain intensity were randomized to a single dose of zavegepant 10 or 20 mg, administered intranasally during a migraine attack (Period 1) and in a non-migraine period (Period 2). Blood samples were collected pre-dose and at pre-specified intervals up to 24 h post-dose for plasma zavegepant concentration measurement. Safety was monitored throughout, and efficacy (migraine pain intensity score, nausea, photophobia, phonophobia, aura, and functional disability) assessed during Period 1. Plasma zavegepant pharmacokinetic parameters were calculated by standard noncompartmental methods, including maximum plasma concentration (Cmax), area under plasma concentration-time curve from time zero to infinity (AUC0-inf), and time of Cmax (Tmax). A total of 37 participants were evaluable for pharmacokinetics. Following administration of zavegepant 10 mg, geometric mean ratios for Period 1/Period 2 were 82.8% (90% confidence interval [CI] 60.5-113.2) for Cmax and 90.1% (90% CI 70.2-115.5) for AUC0-inf. Following administration of zavegepant 20 mg, geometric mean ratios for Period 1/Period 2 were 72.5% (90% CI 57.9-90.8) for Cmax and 73.4% (90% CI 58.8-91.7) for AUC0-inf. Averaging over the study period, geometric mean ratios for zavegepant 20 mg/10 mg were 142.5% (90% CI 118.6-171.4) for Cmax and 157.0% (90% CI 133.6-184.5) for AUC0-inf. Median Tmax was 0.5 h for both doses regardless of Period. Zavegepant was well tolerated in both study periods and effective during Period 1 at both dose levels. There was no apparent correlation between concentration at 0.5 h or 2 h post-dose and efficacy outcomes. Zavegepant exposure was comparable during a migraine attack and a non-migraine period, particularly at the therapeutic dose of 10 mg. When averaging over migraine and non-migraine periods, there was a less-than-dose proportional increase in zavegepant exposure when the dose was doubled from 10 to 20 mg. The median Tmax was 0.5 h regardless of migraine attack or dose. Zavegepant 10 and 20 mg exhibited favorable safety profiles during migraine attacks and non-migraine periods, and were effective to relieve pain, associated symptoms, and functional disability during migraine attacks, with no apparent correlation between zavegepant concentration and efficacy outcomes.

Zolmitriptan niosomal transdermal patches: combating migraine via epigenetic and endocannabinoid pathways and reversal of migraine hypercoagulability.

Conventional zolmitriptan (ZOL) has limited oral bioavailability, many adverse effects, and poor membrane penetrability that negatively influences its accessibility to its 5-HT1B/1D receptor binding pocket, located transmemberanous. This work aimed at preparing transdermal ZOL-nanoformulation (niosomes) to surpass these limitations and to explore novel antimigraine mechanisms for ZOL via modulation of the epigenetically-altered chronification genes (RAMP-1, NPTX-2) or microRNAs and affecting the endocannabinoid CB-1/MAPK pathway. The prepared ZOL niosomes (Fsp60/6-1:1) exhibited %EE of 57.28%, PS of 472.3nm, PDI of 0.366, and ZP of -26 mV were cast into patch with content uniformity of 93.12%, maintained endurance after 200-times folding, no interaction between its components (FT-IR), a biphasic release pattern and good stability after storage at 4°C for 6 months. In-vivo ZOL-patch application in rats with nitroglycerin-induced migraine showed significant management of migraine pain symptoms and photophobia assessed behaviorally, decreased brain levels of the trigeminal neuronal activation marker (c-fos), the migraine pain neurotransmitter (CGRP) and the serum levels of different migraine pain markers (substance P, nitric-oxide, and TNF-α). It also significantly decreased RAMP-1, NPTX-2, miR-382-5p, and CB-1/MAPK gene expression reflecting improved efficacy and brain receptors delivery to a much greater extent than conventional ZOL has done. Additionally, this nanoformulation significantly opposed migraine-induced platelet activation and hypercoagulable status in both central and peripheral circulations as evidenced by the significant decrease in adenosine diphosphate, thrombin, factor X, CD41, and Von-Willebrand factor levels assessed peripherally and centrally. TPFsp60/6-1:1 significantly improved ZOL efficacy and accessibility to brain-receptors to a much greater extent than conventional ZOL-solution.KeywordsEndocannabinoid receptors; Epigenetically-altered genes; Hemostatic pathways; Niosomal patch; Transdermal; Zolmitriptan.

Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches

BackgroundIn addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors.MethodsIn a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague–Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration.ResultsBoth doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP.ConclusionsThe findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine.

Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.

Migraine is a prevalent neurological disorder, particularly among individuals aged 20-50 years, with significant social and economic impacts. Despite its high prevalence, the pathogenesis of migraine remains unclear. In this review, we provide a comprehensive overview of cortical spreading depolarization/depression (CSD) and its close association with migraine aura, focusing on its role in understanding migraine pathogenesis and therapeutic interventions. We discuss historical studies that have demonstrated the role of CSD in the visual phenomenon of migraine aura, along with modern imaging techniques confirming its propagation across the occipital cortex. Animal studies are examined to indicate that CSD is not exclusive to migraines; it also occurs in other neurological conditions. At the cellular level, we review how CSD is characterized by ionic changes and excitotoxicity, leading to neuronal and glial responses. We explore how CSD activates the trigeminal nervous system and upregulates the expression of calcitonin gene-related peptides (CGRP), thereby contributing to migraine pain. Factors such as genetics, obesity, and environmental conditions that influence the CSD threshold are discussed, suggesting potential therapeutic targets. Current treatments for migraine, including prophylactic agents and CGRP-targeting drugs, are evaluated in the context of their expected effects on suppressing CSD activity. Additionally, we highlight emerging therapies such as intranasal insulin-like growth factor 1 and vagus nerve stimulation, which have shown promise in reducing CSD susceptibility and frequency. By elucidating the molecular and cellular mechanisms of CSD, this review aims to enhance the understanding of migraine pathogenesis and support the development of targeted therapeutic strategies.

Clinical Efficacy of Auricular Vagus Nerve Stimulation in the Treatment of Chronic and Acute Pain: A Systematic Review and Meta-analysis.

Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS-needle electrodes) and transcutaneous (tVNS-surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges' g/mean difference of - 1.95 (95% confidence interval [CI]: - 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (- 5.40 [- 8.94; - 1.85] vs. - 1.00 [- 1.55; - 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with - 0.70 [- 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12months was shown. Overall, aVNS was very well tolerated. This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes.

Assessment of Bone Mineral Density Over 1 Year in a Cross-Sectional Cohort of Migraine Patients Receiving Anti-CGRP Monoclonal Antibodies.

Calcitonin gene-related peptide (CGRP), implicated in migraine pain, also possesses bone anabolic properties, which leads to the possibility that monoclonal antibodies targeting CGRP (anti-CGRPs) might increase the risk of bone density abnormalities. The objective of this study was to explore bone mineral density abnormalities in a cohort of migraine patients treated with anti-CGRPs. This was a single-center, cross-sectional, cohort study including migraine patients who underwent a densitometry assessment during anti-CGRP treatment. We assessed the frequency of osteopenia or osteoporosis (OSTEO+ status), defined as a bone mineral density T-score of -1 to -2.5, and <-2.5 standard deviations from the young female adult mean, respectively. Additionally, the association of OSTEO+ status with anti-CGRP treatment duration and primary osteoporosis' risk factors was investigated using logistic regression models. Data from 51 patients (43 female, mean age 46 ± 13.9 years) were evaluated. The mean duration of anti-CGRP treatment was 15.7 (±11.8) months. Twenty-seven patients (53%) were OSTEO+ (n = 22 osteopenia; n = 5 osteoporosis). In the final model, menopause [odds ratio 11.641 (95% confidence interval 1.486-91.197), p = 0.019] and anti-seizure drug use [odds ratio 12.825 (95% confidence interval 1.162-141.569), p = 0.037] were associated with OSTEO+ status. In our cohort of migraine patients, no evidence of an association between anti-CGRP treatment duration and an increasing risk of bone mineral density abnormalities was found. However, these findings are preliminary and necessitate further longitudinal research with larger cohorts and extended follow-up to be validated.

Anti-inflammatoires non stéroïdiens en prescription médicale facultative : mise au point dans la prise en charge de la douleur aiguë

Non-steroidal anti-inflammatory drugs (NSAIDs) are the second most widely used class of analgesics in France, after paracetamol. Some NSAIDs are available over the counter (OTC), without a prescription, on the advice of a pharmacist. NSAIDs have recently been the subject of safety alerts from France's Agence nationale de sécurité du médicament et des produits de santé (ANSM), highlighting a risk of worsening certain bacterial infections. This signal has not been confirmed by the European Medicines Agency (EMA) although a "risk of complications due to masking of symptoms of infection" has not been ruled out. These divergent messages can be confusing for healthcare professionals. This literature review, based on an analysis of nearly 200 scientific publications, considers the place of NSAIDs in the OTC management of migraine, tension headaches, postoperative analgesia, acute musculoskeletal and joint pain, dysmenorrhea, viral respiratory infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their toxicity. The role of the pharmacist in dispensing NSAIDs without a prescription is also addressed. NSAIDs offer rapid and effective pain management in a context of increasingly challenging access to care. Their safety profile is reassuring and generally well established but could be strengthened by conducting an ad hoc study to rule on the safety signal issued by the ANSM definitively. Pharmacists have the knowledge and tools to ensure the safe dispensing and rational use of NSAIDs, with or without a prescription. The introduction of risk minimization measures, such as decision-support tools, could enable further progress in ensuring the safe dispensing of OTC NSAIDs.

TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models

AimsAccumulating evidence indicates the involvement of TRESK potassium channels in migraine, however, effects of TRESK activation on migraine-related mechanisms remain unclear. We explored effects of TRESK channel modulation on migraine-related behavioral and molecular markers in in-vivo and ex-vivo rat models of migraine. Main methodsThe selective TRESK activator cloxyquin at different doses, the TRESK inhibitor A2764, and the migraine drug sumatriptan were tested alone or in different combinations in nitroglycerin (NTG)-induced in-vivo model, and in ex-vivo meningeal, trigeminal ganglion and brainstem preparations in which CGRP release was induced by capsaicin. Mechanical allodynia, CGRP and c-fos levels in trigeminovascular structures and meningeal mast cells were evaluated. Key findingsCloxyquin attenuated NTG-induced mechanical allodynia, brainstem c-fos and CGRP levels, trigeminal ganglion CGRP levels and meningeal mast cell degranulation and number, in-vivo. It also diminished capsaicin-induced CGRP release from ex-vivo meningeal, trigeminal ganglion and brainstem preparations. Specific TRESK inhibitor A2764 abolished all effects of cloxyquin in in-vivo and ex-vivo. Combining cloxyquin and sumatriptan exerted a synergistic effect ex-vivo, but not in-vivo. SignificanceOur findings provide the experimental evidence for the anti-migraine effect of TRESK activation in migraine-like conditions. The modulation of TRESK channels may therefore be an attractive alternative strategy to relieve migraine pain.

Efficacy of eptinezumab in non-responders to subcutaneous monoclonal antibodies against CGRP and the CGRP receptor: A retrospective cohort study.

Migraine patients unresponsive to calcitonin gene-related peptide (CGRP)(-receptor, -R) monoclonal antibodies (mAbs) may benefit from switching between CGRP(-R) mAbs. However, some patients do not tolerate or respond to any subcutaneous mAbs. This study evaluates the efficacy of the intravenous CGRP mAb eptinezumab in these therapy-refractory patients. In this retrospective cohort study, patients with migraine who previously failed erenumab and at least one CGRP mAb (fremanezumab and/or galcanezumab) received eptinezumab 100 mg, followed by a second dose of 100 mg or 300 mg after 12 weeks. Monthly headache days, monthly migraine days, acute medication days, and migraine pain intensity were recorded from standardized headache diaries during the four weeks before the first infusion (baseline), and during weeks 9-12 and 21-24 of treatment. Patient-reported outcomes were analyzed at baseline, weeks 12, and 24. From January 2023 to February 2024, 41 patients received eptinezumab 100 mg. Of these, 38 (93%) received a second infusion after 12 weeks, with 29 (71%) increasing the dose to 300 mg. The percentage of patients with a ≥30% reduction rate in monthly migraine days was 23.1% at week 12 and 29.7% at week 24. Monthly migraine days decreased from 16.3 ± 8.0 at baseline to 15.4 ± 8.1 days during weeks 9-12 and 14.4 ± 8.0 days during weeks 21-24 (p = 0.07). During weeks 21-24, 38.5% reported a clinically meaningful reduction in HIT-6 scores and 52.4% in MIDAS scores. No adverse events were reported. Eptinezumab may be an effective and well-tolerated option for some treatment-refractory migraine patients unresponsive to subcutaneous CGRP-(R) mAbs.

Intranasal Administration of Standardized Extract of Gotu Kola Leaves Against Nitroglycerine-Induced Recurrent Migraine-Like Pain in Rats

The present study aimed to determine the efficacy of intranasal administration of a standardized extract of Gotu kola, i.e., Centella asiatica (L.) Urban (INDCA-NS) with marker triterpenoids for the prevention of nitroglycerine- (NTG)-induced recurrent migraine in rats. Adult rats of both sexes in a group of 12 were administered intraperitoneal NTG (10 mg/kg) on alternate days (D1 to D9) and once daily intranasal solutions of either vehicle (saline, 50 µL/rat/day), sumatriptan (80 µL/rat/day of 12 mg/ml) as positive control, or INDCA-NS (10, 30, or 100 µg/rat/day) for 21 days. Behavioral and biochemical parameters related to concurrent migraine pain (facial expressions on the grimace scale, thermal hyperalgesia, mechanical allodynia, and plasma and brain levels of pituitary adenylate cyclase-activating polypeptide and nitric oxide), and stress (photophobia and cortisol levels in the brain and serum) were measured. The intranasal administration of INDCA-NS prevented NTG-induced migraine-like pain, photophobia, and stress in a dose-dependent manner. At the same time, sumatriptan alleviated pain and anxiety but not photophobia. In conclusion, the intranasal administration of INDCA-NS showed prophylactic efficacy against recurrent NTG-induced migraine pain in rats.

Pharmacological Effects of Matrine in Nitroglycerine-induced Migraine Pain by Inhibiting Cytokines and Oxidative Stress

Pharmacological Effects of Matrine in Nitroglycerine-induced Migraine Pain by Inhibiting Cytokines and Oxidative Stress

Lignocaine in Migraine Treatment: A Comprehensive Review

Introduction: Migraine is a prevalent and debilitating neurological disorder characterized by recurrent headaches and associated symptoms such as nausea, photophobia, and phonophobia. While conventional treatments exist, a significant subset of patients suffers from refractory migraines, prompting the exploration of alternative therapies like lignocaine. Purpose of the work: This review examines the mechanisms by which lignocaine modulatespain and underscores the potential of lignocaine as a therapeutic option for refractory migraines, while also highlighting the need for continued research to refine its clinical application. Materials and methods: A comprehensive analysis of research papers available on PubMed, Google Scholar, Web of Science, Embase and Scopus was undertaken using the searchterms encompassing the following keywords: chronic migraine / lignocaine migraine / migraine treatment/ migraine pain mechanism / migraine chronic pain mechanism / lignocaine and ketamine migraine / lignocaine adverse effects / lignocaine safety / refractory migraine. Results: Lignocainehas shown promise in alleviating both acute and chronic migraine pain. However, its use requires careful patient selection and monitoring due to potential side effects, such as cardiac and central nervous system toxicity. Despite these risks, the favorable safety profile and efficacy of lignocaine make it a valuable option in migraine management. Future research should focus on optimizing dosing protocols, evaluating long-term outcomes, and identifying biomarkers to guide patient selection.

FREQUENCY OF MIGRAINE-RELATED DEPRESSION AMONG MIGRAINEURS IN PAKISTAN: A CROSS-SECTIONAL STUDY

Depressive disorders are among the leading causes of disability globally and can further complicate the clinical manifestation if coupled with other comorbidities. Objective: The main objective of the study is to find the frequency of migraine-related depression among migraineurs in Pakistan. Methods: This cross-sectional study was conducted at Fauji Foundation Hospital Rawalpindi from January 2024 to June 2024. Data were collected from 240 patients. Data were collected through a designed questionnaire which contain all data related to depression and awareness of patients. All the data related to sociodemographic factors, history, disease duration, and frequency of migraine attacks were noted. Results: Data were collected from 240 participants with a mean age of 35.4±9.8 years. Most patients (60%) fall in the 30-45 age range. Regarding the duration of migraines, 45.8% of patients had suffered for 1-5 years, while 41.7% had migraines for more than 5 years. The majority of participants (41.7%) experienced 3-4 migraine attacks per month. Regarding pain severity, half of the patients (50%) reported moderate pain, while 33.3% experienced severe pain. The results showed that 66.7% of migraine patients experienced some level of depression, as measured by the PHQ-9 scale. Conclusion: It is concluded that depression is highly prevalent among migraine sufferers in Pakistan, with more than two-thirds of patients experiencing some form of depressive symptoms. The severity of depression is significantly associated with migraine frequency, duration, and pain intensity.

Calcitonin Gene-Related Peptide Monoclonal Antibodies: Key Lessons from Real-World Evidence.

The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology.

The link between cutaneous allodynia and pain/sensitivity in teeth and gums during migraine episodes

BackgroundMigraine is one of the most common primary headaches worldwide, while toothache is the most common pain in the orofacial region. The association of migraine pain, and oral pain is unknown. This study aims to investigate the association between migraine and dental and gingival pain with the presence of allodynia.MethodsA questionnaire comprising demographic data with the ID-Migraine (IDM) tool, an Allodynia Symptom Checklist (ASC), and inquiries about pain and sensitivity in the teeth and gums during migraine attacks was administered to the participants and 762 responded the survey. The study classified participants based on the ASC, and the relationship between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks was analyzed. The statistical analyses utilized Chi-square tests and the Fisher-Exact test.ResultsAmong 762 migraine patients, 430 (56.44%) were classified as allodynia (+), while 332 (43.56%) were classified as allodynia (−) (p < 0.001). Additionally, 285 participants (37.5%) reported experiencing pain and sensitivity in the teeth and gums during migraine attacks, with a significant relationship observed between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks (p < 0.001).ConclusionThe findings of this study have important clinical implications. For migraine patients who are non-allodynic, the presence of pain and sensitivity in their teeth and gums during migraine attacks may indicate underlying dental diseases or the need for dental treatment especially root canal treatment. However, for allodynic patients, such symptoms may not necessarily indicate the presence of dental diseases or the need for dental treatment especially root canal treatment. These results underscore the significance of considering the presence of allodynia in the assessment and management of oral symptoms during migraine attacks.

The impact of electrotherapy on the quality of life of patients suffering from chronic migraine and cervicalgia

Objective. To evaluate the effect of electrotherapy on quality of life in patients with chronic migraine and neck pain. Material and methods. The study included 45 patients with chronic migraine and neck pain, divided into two groups: the first group (n=25) received treatment with transcutaneous electrical nerve stimulation (TENS), the second group (n=20) received botulinum toxin type A injections PREEMPT scheme. The results were assessed using the MIDAS, HIT-6 and NDI questionnaires before the start of treatment and one month after it began. Results. The use of electrotherapy caused a greater reduction in disability and improved quality of life compared to botulinum toxin. The data obtained indicate the high effectiveness of electrotherapy and the need for its further use in clinical practice to improve the condition of patients with chronic migraine and neck pain.

Patient with cryptogenic cirrhosis

Cryptogenic cirrhosis is cirrhosis of uncertain etiology, with no definitive clinical and histological criteria for a specific disease. More than half of such patients are women, the average age is about 60, and patients generally have only mild liver enzyme abnormalities. Cryptogenic cirrhosis's pathophysiology is unknown; therefore, further research is required to elucidate the underlying etiology. The problem of liver cirrhosis is extremely important since this pathology occurs mainly in young and healthy people. In patients with cryptogenic cirrhosis, aminotransferase (AST and ALT) levels are usually only mildly elevated or normal. In our case report, a 41-year-old male patient was approved to the emergency department due to migraine pain. Liver enzymes were high in the blood analysis taken from the patient. As a result of the liver ultrasound carried out on the patient, it was reported to have decreased liver size and irregular boundaries and compatible with chronic liver disease. The patient used various analgesics due to migraine in his 20s. However, no cause could be identified for the patient's liver failure.

The perception gap on migraine: a survey study of the migraine patients, family members, and physicians

Migraine is a disease that is difficult to be recognized by those around the patients, even though it causes significant hindrances. In this study, we conducted an exploratory comparison of the perceptions on migraine among patients, family members living with them, and physicians treating migraine patients. Patients and family members shared a common understanding on the pain of migraine, and hoped to spend more/better time together as a family. However, although family members felt compassion for the patients, lack of understanding by and patients' concern for the surroundings led to feelings of resignation and endurance on the side of patients. Regarding physicians' medical care, our results suggested the importance to understand the wishes and obstacles of each patient and to propose treatment accordingly. In order to reduce the burden of migraine, it is necessary to create an environment and raise awareness that allows people around the patients to understand and support the pain and hopes that each patient feels.

Pharmacological investigation of genistein for its therapeutic potential against nitroglycerin-induced migraine headache.

Migraine, typically occurs on one side of the head, lasts for hours to days. Trigemino-vascular system (TVS) plays a vital role in pain generation, with neurogenic inflammation and oxidative stress playing key roles in its pathophysiology. This study aimed to investigate genistein's potential as anti-inflammatory and anti-oxidant agent in mitigating migraine pain. Genistein (20 and 50mg/kg) was administered intraperitoneally (IP) to nitroglycerin (NTG; 10mg/kg)-induced migraine model in rats. Behavioral analysis, antioxidant assay, immunohistochemistry (IHC), histopathological examination, ELISA, and RT-PCR were conducted to evaluate the antimigraine potential of genistein. In-silico analysis showed genestien's ACE values of -4.8 to -9.2 Kcal/mol against selected protein targets. Genistein significantly reversed mechanical and thermal nociception, light phobicity, and head scratching; increased the intensities of GST, GSH, catalase; and down regulated lipid peroxidase (LPO) in cortex and trigeminal nucleus caudalis (TNC). It also reduced Nrf2, NF-kB, and IL6 expression, analyzed through IHC, improved histopathological features, and increased COX-2 and decreased PPAR-γ expressions, while RT-PCR analysis revealed increased PPAR-γ expressions in genistein-treated rats. Genistein exhibited potent antioxidant and anti-inflammatory properties in migraine treatment, acting through multifactorial mechanisms by modulating the expression of numerous proteins in the region cortex and TNC.