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Migraine is a complex neurovascular disorder characterized by recurrent attacks of pain and other associated symptoms. Emotional-affective aspects are important components of pain, but so far they have been little explored in animal models of migraine. In this study, we aimed to explore the correlation between trigeminal hyperalgesia and affective status or behavioral components in a migraine-specific animal model. Male Sprague-Dawley rats were treated with nitroglycerin (10 mg/kg, i.p.) or its vehicle. Four hours later, anxiety, motor/exploratory behavior and grooming (a nociception index) were evaluated with the open field test. Rats were then exposed to formalin in the orofacial region to evaluate trigeminal hyperalgesia. The data analysis shows an inverse correlation between trigeminal hyperalgesia and motor or exploratory behavior, and a positive association with anxiety-like behavior or self-grooming. These findings further expand on the translational value of the migraine-specific model based on nitroglycerin administration and prompt additional parameters that can be investigated to explore migraine disease in its complexity.
Learn More >Co-occurring pain conditions that affect overlapping body regions are complicated by the distinction between primary versus secondary pain conditions. We investigate the occurrence of headache and painful temporomandibular disorder (TMD) in a community-based, cross-sectional study of U.S. adults in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA-II) study. A specific goal was to determine if headache attributed to TMD is separable from primary headache.Using DC/TMD and ICHD-3 criteria, three groups of individuals were created: a) headache without TMD; b) headache comorbid with TMD; and c) headache attributed to TMD. Regression models compared study groups according to demographic and comorbid characteristics, and post-hoc contrasts tested for differences. Descriptive statistics and Cohen's d effect size were computed, by group, for each predictor variable. Differences in continuous predictors were analyzed using one-way ANOVA.Nearly all demographic and comorbid variables distinguished the combined headache and TMD groups from the group with headache alone. Relative to the reference group with primary headache alone, markers related to headache, TMD, somatic pain processing, psychosocial, and health conditions were substantially greater in both headache comorbid with TMD and headache attributed to TMD, attesting to their qualitative similarities. However, effect sizes relative to the reference group were large for headache comorbid with TMD and larger again for headache attributed to TMD, attesting to their separability in quantitative terms.In summary, the presence of overlapping painful TMD and headache adds substantially to the biopsychosocial burden of headache and points to the importance of comprehensive assessment and differential management.
Learn More >Migraine is a common and disabling neurological disorder, with several manifestations, of which pain is just one. Despite its worldwide prevalence, there remains a paucity of targeted and effective treatments for the condition, leaving many of those affected underserved by available treatments. Work over the last 30+ years has recently led to the emergence of the first targeted acute and preventive treatments in our practice since the triptan era in the early 1990s, which are changing the landscape of migraine treatment. These include the monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. Evolving work on novel therapeutic targets, as well as continuing to exploit drugs used in other disorders that may also have a therapeutic effect in migraine, is likely to lead to more and more treatments being able to be offered to migraineurs. Future work involves the development of agents that lack vasoconstrictive effects, such as lasmiditan, do not contribute to medication overuse, such as the gepants, and do not interact with other drugs that may be used for the disorder, as well as agents that can act both acutely and preventively, thereby utilising the quantum between acute and preventive drug effects which has been demonstrated with different migraine drugs before. Here we discuss the evolution of oral migraine treatments over the last 5 years, including those that have gained regulatory approval and reached clinical practice, those in development and potential other targets for the future.
Learn More >Multiple sclerosis (MS) is a chronic inflammatory disease leading to multifocal neuronal demyelination and axonal damage in the central nervous system (CNS). MS symptoms vary widely but typically do not include headaches. A large spectrum of headaches manifestations was reported as comorbidities in MS and results in additional disability. Migraine, tension-type headache and cluster headache are the most frequently reported primary headache syndromes in patients with MS (pwMS). Secondary causes of headache should be excluded (cerebral vein thrombosis, CNS or systemic infection, cervical and/or cranial trauma, headaches associated with psychiatric disorders, medication overuse headache, etc.) in this particular population. A careful medical history and general and neurological examinations and sometimes further investigations may be needed to rule out secondary headache syndromes. In pwMS, the headache could be an adverse effect of the disease-modifying therapies or a complication of pain medication overuse prescribed to relieve other causes of pain related to MS (neuropathic pain, mechanical pain, pain associated with spasticity, etc.). Migraine-type headache occurs in pwMS more frequently than in the general population. It can precede the disease onset, be associated with relapses, or appear during the MS course. A predominance of brainstem inflammatory lesions is described on magnetic resonance imaging (MRI) in MS patients with migraine. The relationship between both conditions remains unclear. Migraine and MS occur in the same demographic groups with similar background factors, including gender, hormonal status, and psychological features (anxiety, depression, stress). An early diagnosis and adequate treatment of migraine in MS patients are important to improve their quality of life. In this review, we focus on the relationship between MS and Migraine, discuss the differential diagnoses of migraine in pwMS, and describe its management in this particular context.
Learn More >Migraine is a common and complex neurovascular disorder. Clinically, the diagnosis of migraine mainly relies on scales, but the degree of pain is too subjective to be a reliable indicator. It is even more difficult to diagnose the medication-overuse headache, which can only be evaluated by whether the symptom is improved after the medication adjustment. Therefore, an objective migraine classification system to assist doctors in making a more accurate diagnosis is needed. In this research, 13 healthy subjects (HC), 9 chronic migraine subjects (CM), and 12 medication-overuse headache subjects (MOH) were measured by functional near-infrared spectroscopy (fNIRS) to observe the change of the hemoglobin in the prefrontal cortex (PFC) during the mental arithmetic task (MAT). Our model shows the sensitivity and specificity of CM are 100% and 75%, and that of MOH is 75% and 100%.The results of the classification of the three groups prove that fNIRS combines with machine learning is feasible for the migraine classification.
Learn More >Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects.
Learn More >The ketogenic diet (KD) is gaining attention as a preventive treatment for migraine, which is sustained by many pre-clinical and clinical data. KD is also used for weight loss, and there is a relation between migraine and weight excess, but it is speculated that KD efficacy on migraine may go beyond this effect. We conducted a retrospective observational study on 23 migraine patients who received a KD and were evaluated at the baseline and then after 3 months both from a neurological and a nutritional point of view, including body mass composition analysis. We observed a reduction in monthly headache days (12.5 ± 9.5 vs. 6.7 ± 8.6; < 0.001) and in days of acute medication intake (11.06 ± 9.37 vs. 4.93 ± 7.99; = 0.008). We also observed a reduction in patients' weight (73.8 ± 15.2 vs. 68.4 ± 14.6; < 0.001) and BMI (26.9 ± 6.2 vs. 23.7 ± 8.1; < 0.001) with a decrement of the fat mass (28.6 ± 12.5 vs. 20.6 ± 9.8; < 0.001). Patients who responded to KD and those who did not had no differences with respect to weight or fat mass loss. These data corroborate the utilization of KD as a preventive treatment for migraine and suggest that the efficacy of such an intervention is not only due to weight or fat mass loss but probably relies on other mechanisms specific to KD.
Learn More >The efficacy of ubrogepant 50 mg versus 100 mg daily for migraine remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of ubrogepant 50 mg versus 100 mg daily on treatment in migraine patients. We have searched PubMed, EMbase, Web of science, EBSCO, Cochrane library databases and SCOPUS through March 21, 2022 for randomized controlled trials (RCTs) assessing the effect of ubrogepant 50 mg versus 100 mg on treatment efficacy in migraine patients. This meta-analysis was performed using the random-effect model. Three RCTs were included in the meta-analysis. Overall, compared with ubrogepant 100 mg in migraine patients, ubrogepant 50 mg obtained comparable pain freedom at 2 hours (OR =0.86; 95% CI =0.64 to 1.15; P = 0.310), sustained pain freedom 2-24 hours (OR =0.76; 95% CI =0.54 to 1.07; P = 0.110), photophobia absence at 2 h (OR =0.80; 95% CI =0.63 to 1.02; P = 0.070), phonophobia absence at 2 h (OR =1.07; 95% CI =0.82 to 1.40; P = 0.620) and nausea absence at 2 h (OR =1.02; 95% CI =0.79 to 1.32; P = 0.880). In terms of safety, adverse events was found to be increased in ubrogepant 100 mg as compared to ubrogepant 50 mg (OR =0.81; 95% CI =0.67 to 0.99; P = 0.040), and there was no statistical difference of serious adverse events between two groups (OR =0.87; 95% CI =0.40 to 1.91; P = 0.720). Ubrogepant 50 mg and 100 mg may be equally effective to alleviate migraine, but ubrogepant 100 mg led to increase incidence of adverse events.
Learn More >Unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain.
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