The Journal of Headache and Pain最新文献

{"title":"HMGB1 in the mPFC governs comorbid anxiety in neuropathic pain.","authors":"Yu Du,&nbsp;Ceng-Lin Xu,&nbsp;Jie Yu,&nbsp;Keyue Liu,&nbsp;Shi-Da Lin,&nbsp;Ting-Ting Hu,&nbsp;Feng-Hui Qu,&nbsp;Fang Guo,&nbsp;Guo-Dong Lou,&nbsp;Masahiro Nishibori,&nbsp;Wei-Wei Hu,&nbsp;Zhong Chen,&nbsp;Shi-Hong Zhang","doi":"10.1186/s10194-022-01475-z","DOIUrl":"https://doi.org/10.1186/s10194-022-01475-z","url":null,"abstract":"<p><strong>Background: </strong>Whether neuroinflammation causes comorbid mood disorders in neuropathic pain remains elusive. Here we investigated the role of high mobility group box 1 protein (HMGB1), a proinflammatory cytokine, in the medial prefrontal cortex (mPFC) in anxiety comorbidity of neuropathic pain.</p><p><strong>Methods: </strong>Neuropathic pain was induced by partial transection of the infraorbital nerve (p-IONX) or partial sciatic nerve ligation (PSL) in mice and evaluated by measuring nociceptive thresholds to mechanical and heat stimulation. Anxiety-like behaviors were assessed by elevated plus maze, light dark box and open field tests. Aversive or anti-aversive effect was detected by conditioned place preference test. Neuronal activity was evaluated by single-unit and patch clamp recordings. The contribution of mPFC pyramidal neurons to anxiety was further examined by selectively inhibiting them by optogenetics. HMGB1 expression was measured by immunohistochemistry and western blotting. Antagonism of HMGB1 was achieved by injecting anti-HMGB1 monoclonal antibody (mAb) intracerebrally or intraperitoneally.</p><p><strong>Results: </strong>Anxiety-like behaviors were presented earlier after p-IONX than after PSL. HMGB1 expression was upregulated in the mPFC temporally in parallel to anxiety onset, rather than in other regions associated with anxiety. The upregulation of HMGB1 expression and its translocation from the nucleus to cytoplasm in the mPFC occurred predominantly in neurons and were accompanied with activation of microglia and astrocytes. Infusion of anti-HMGB1 mAb into the mPFC during the early and late phases after either p-IONX or PSL alleviated anxiety-like behaviors and aversion without changing pain sensitization, while local infusion of exogenous ds-HMGB1, the proinflammatory form of HMGB1, into the mPFC induced anxiety and aversion but not pain sensitization in naïve mice. In addition to reversing established pain sensitization and anxiety simultaneously, intraperitoneal injection of anti-HMGB1 mAb reduced HMGB1 upregulation and suppressed the hyperexcitability of layer 2/3 pyramidal neurons in the mPFC after p-IONX. Moreover, optogenetic inhibition of mPFC pyramidal neurons alleviated anxiety in p-IONX mice.</p><p><strong>Conclusion: </strong>These results demonstrate that HMGB1 in the mPFC drives and maintains anxiety comorbidity in neuropathic pain by increasing the excitability of layer 2/3 pyramidal neurons, and justify antagonism of HMGB1, e.g., neutralization by mAb, as a promising therapeutic strategy for neuropathic pain with anxiety comorbidity.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"102"},"PeriodicalIF":7.4,"publicationDate":"2022-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9382735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40616723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Avoid or seek light - a randomized crossover fMRI study investigating opposing treatment strategies for photophobia in migraine.","authors":"Eva Matt,&nbsp;Tuna Aslan,&nbsp;Ahmad Amini,&nbsp;Kardelen Sariçiçek,&nbsp;Stefan Seidel,&nbsp;Paul Martin,&nbsp;Christian Wöber,&nbsp;Roland Beisteiner","doi":"10.1186/s10194-022-01466-0","DOIUrl":"https://doi.org/10.1186/s10194-022-01466-0","url":null,"abstract":"<p><strong>Background: </strong>Photophobia, the aberrantly increased sensitivity to light, is a common symptom in migraine patients and light discomfort is frequently found as a trigger for migraine attacks. In behavioral studies, planned exposure to light was found to reduce headache in migraine patients with photophobia, potentially by increasing habituation to this migraine trigger. Here, we aimed to elucidate neurophysiological mechanisms of light exposure versus light deprivation in migraine patients using functional magnetic resonance imaging (fMRI).</p><p><strong>Methods: </strong>Ten migraine patients (9 female, age = 28.70 ± 8.18 years) and 11 healthy controls (9 female, age = 23.73 ± 2.24 years) spent one hour on 7 consecutive days exposed to flashing light (Flash) or darkness (Dark) using a crossover design with a wash-out period of 3 months. Study participants kept a diary including items on interictal and ictal photophobia, presence and severity of headache 7 days before, during and 7 days after the interventions. One week before and one day after both interventions, fMRI using flickering light in a block design was applied. Functional activation was analyzed at whole-brain level and habituation of the visual cortex (V1) was modeled with the initial amplitude estimate and the corrected habituation slope.</p><p><strong>Results: </strong>Mean interictal photophobia decreased after both interventions, but differences relative to the baseline did not survive correction for multiple comparisons. At baseline, flickering light induced activation in V1 was higher in the patients compared to the controls, but activation normalized after the Flash and the Dark interventions. V1 habituation indices correlated with headache frequency, headache severity and ictal photophobia. In the Flash condition, the individual change of headache frequency relative to the baseline corresponded almost perfectly to the change of the habituation slope compared to the baseline.</p><p><strong>Conclusions: </strong>On average, light exposure did not lead to symptom relief, potentially due to the short duration of the intervention and the high variability of the patients' responses to the intervention. However, the strong relationship between visual cortex habituation and headache symptoms and its modulation by light exposure might shed light on the neurophysiological basis of exposure treatment effects.</p><p><strong>Trial registration: </strong>NCT05369910 (05/06/2022, retrospectively registered).</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"99"},"PeriodicalIF":7.4,"publicationDate":"2022-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9367056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40601551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine.","authors":"Wei Zhang,&nbsp;Ming Lei,&nbsp;Qianwen Wen,&nbsp;Dunke Zhang,&nbsp;Guangcheng Qin,&nbsp;Jiying Zhou,&nbsp;Lixue Chen","doi":"10.1186/s10194-022-01469-x","DOIUrl":"https://doi.org/10.1186/s10194-022-01469-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The pathogenesis of chronic migraine remains unresolved. Recent studies have affirmed the contribution of GLUA1-containing AMPA receptors to chronic migraine. The dopamine D2 receptor, a member of G protein-coupled receptor superfamily, has been proven to have an analgesic effect on pathological headaches. The present work investigated the exact role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A chronic migraine model was established by repeated inflammatory soup stimulation. Mechanical, periorbital, and thermal pain thresholds were assessed by the application of von Frey filaments and radiant heat. The mRNA and protein expression levels of the dopamine D2 receptor were analyzed by qRT‒PCR and western blotting. Colocalization of the dopamine D2 receptor and the GLUA1-containing AMPAR was observed by immunofluorescence. A dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride), a PI3K inhibitor (LY294002), a PI3K pathway agonist (740YP), and a GLUA1-containing AMPAR antagonist (NASPM) were administered to confirm the effects of the dopamine D2 receptor, the PI3K pathway and GULA1 on central sensitization and the GLUA1-containing AMPAR trafficking. Transmission electron microscopy and Golgi-Cox staining were applied to assess the impact of the dopamine D2 receptor and PI3K pathway on synaptic morphology. Fluo-4-AM was used to clarify the role of the dopamine D2 receptor and PI3K signaling on neuronal calcium influx. The Src family kinase (SFK) inhibitor PP2 was used to explore the effect of Src kinase on GLUA1-containing AMPAR trafficking and the PI3K signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Inflammatory soup stimulation significantly reduced pain thresholds in rats, accompanied by an increase in PI3K-P110β subunit expression, loss of dopamine receptor D2 expression, and enhanced GLUA1-containing AMPA receptor trafficking in the trigeminal nucleus caudalis (TNC). The dopamine D2 receptor colocalized with the GLUA1-containing AMPA receptor in the TNC; quinpirole, LY294002, and NASPM alleviated pain hypersensitivity and reduced GLUA1-containing AMPA receptor trafficking in chronic migraine rats. Sulpiride aggravated pain hypersensitivity and enhanced GLUA1 trafficking in CM rats. Importantly, the anti-injury and central sensitization-mitigating effects of quinpirole were reversed by 740YP. Both quinpirole and LY294002 inhibited calcium influx to neurons and modulated the synaptic morphology in the TNC. Additional results suggested that DRD2 may regulate PI3K signaling through Src family kinases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Modulation of GLUA1-containing AMPA receptor trafficking and central sensitization by the dopamine D2 receptor via the PI3K signaling pathway may contribute to the pathogenesis of chronic migraine in rats, and the dopamine D2 receptor could be a valuable candidate for chroni","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"98"},"PeriodicalIF":7.4,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40696534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total tenderness score and pressure pain thresholds in persistent post-traumatic headache attributed to mild traumatic brain injury.","authors":"Håkan Ashina,&nbsp;Haidar Muhsen Al-Khazali,&nbsp;Afrim Iljazi,&nbsp;Sait Ashina,&nbsp;Faisal Mohammad Amin,&nbsp;Henrik Winther Schytz","doi":"10.1186/s10194-022-01457-1","DOIUrl":"https://doi.org/10.1186/s10194-022-01457-1","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether persistent post-traumatic headache attributed to mild traumatic brain injury (TBI) is associated with more pronounced pericranial tenderness and lower pressure pain thresholds (PPTs) in the head and neck region, compared with healthy controls.</p><p><strong>Methods: </strong>Patients with persistent post-traumatic headache (n = 100) and age- and gender-matched healthy controls (n = 100) were included between July 2018 and June 2019. Total tenderness score (TTS) was used to assess pericranial tenderness by bilateral manual palpation in eight muscles or tendon insertions. Summation was then used to calculate a TTS from 0 to 48 based on individual right- and left-sided scores; higher TTS score indicated more pronounced pericranial tenderness. PPTs were examined in m. temporalis and m. trapezius (upper and middle part) using an electronic pressure algometer that applies increasing blunt pressure at a constant rate.</p><p><strong>Results: </strong>The TTS score was higher in patients with persistent post-traumatic headache (median, 21; IQR, 12-31), compared with healthy controls (median, 10; IQR, 6-17; P < .001). PPTs were lower in patients with persistent post-traumatic headache than in controls in both the left-sided m. temporalis (mean ± SD, 157.5 ± 59.9 vs. 201.1 ± 65.2; P < .001) and right-sided m. temporalis (mean ± SD, 159.5 ± 63.8 vs. 212.3 ± 61.9; P < .001). Furthermore, patients with persistent post-traumatic headache also had lower left- and right-sided PPTs in the upper as well as middle part of m. trapezius, compared with healthy controls; all P values were .05 or less.</p><p><strong>Conclusions: </strong>Among patients with persistent post-traumatic headache, pericranial tenderness was more pronounced and PPTs in the head and neck region were lower than in healthy controls free of headache and mild TBI. Further research is needed to better understand the involvement of pericranial myofascial nociceptors in the disease mechanisms underlying post-traumatic headache.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"96"},"PeriodicalIF":7.4,"publicationDate":"2022-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40596188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Headache-related circuits and high frequencies evaluated by EEG, MRI, PET as potential biomarkers to differentiate chronic and episodic migraine: Evidence from a systematic review.","authors":"Javier Gomez-Pilar, Víctor Martínez-Cagigal, David García-Azorín, Carlos Gómez, Ángel Guerrero, Roberto Hornero","doi":"10.1186/s10194-022-01465-1","DOIUrl":"10.1186/s10194-022-01465-1","url":null,"abstract":"<p><strong>Background: </strong>The diagnosis of migraine is mainly clinical and self-reported, which makes additional examinations unnecessary in most cases. Migraine can be subtyped into chronic (CM) and episodic (EM). Despite the very high prevalence of migraine, there are no evidence-based guidelines for differentiating between these subtypes other than the number of days of migraine headache per month. Thus, we consider it timely to perform a systematic review to search for physiological evidence from functional activity (as opposed to anatomical structure) for the differentiation between CM and EM, as well as potential functional biomarkers. For this purpose, Web of Science (WoS), Scopus, and PubMed databases were screened.</p><p><strong>Findings: </strong>Among the 24 studies included in this review, most of them (22) reported statistically significant differences between the groups of CM and EM. This finding is consistent regardless of brain activity acquisition modality, ictal stage, and recording condition for a wide variety of analyses. That speaks for a supramodal and domain-general differences between CM and EM that goes beyond a differentiation based on the days of migraine per month. Together, the reviewed studies demonstrates that electro- and magneto-physiological brain activity (M/EEG), as well as neurovascular and metabolic recordings from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), show characteristic patterns that allow to differentiate between CM and EM groups.</p><p><strong>Conclusions: </strong>Although a clear brain activity-based biomarker has not yet been identified to distinguish these subtypes of migraine, research is approaching headache specialists to a migraine diagnosis based not only on symptoms and signs reported by patients. Future studies based on M/EEG should pay special attention to the brain activity in medium and fast frequency bands, mainly the beta band. On the other hand, fMRI and PET studies should focus on neural circuits and regions related to pain and emotional processing.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"95"},"PeriodicalIF":0.0,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40585123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Burden of tension-type headache in the Middle East and North Africa region, 1990-2019.","authors":"Saeid Safiri,&nbsp;Ali-Asghar Kolahi,&nbsp;Maryam Noori,&nbsp;Seyed Aria Nejadghaderi,&nbsp;Armin Aslani,&nbsp;Mark J M Sullman,&nbsp;Mehdi Farhoudi,&nbsp;Mostafa Araj-Khodaei,&nbsp;Gary S Collins,&nbsp;Jay S Kaufman,&nbsp;Kurosh Gharagozli","doi":"10.1186/s10194-022-01454-4","DOIUrl":"https://doi.org/10.1186/s10194-022-01454-4","url":null,"abstract":"","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"94"},"PeriodicalIF":7.4,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40577016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients.","authors":"Ke Li,&nbsp;Shuping Sun,&nbsp;Zhanyou Xue,&nbsp;Sufen Chen,&nbsp;Chunyang Ju,&nbsp;Dongmei Hu,&nbsp;Xiaoyu Gao,&nbsp;Yanhong Wang,&nbsp;Dan Wang,&nbsp;Jianjun Chen,&nbsp;Li Li,&nbsp;Jing Liu,&nbsp;Mingjie Zhang,&nbsp;Zhihua Jia,&nbsp;Xun Han,&nbsp;Huanxian Liu,&nbsp;Mianwang He,&nbsp;Wei Zhao,&nbsp;Zihua Gong,&nbsp;Shuhua Zhang,&nbsp;Xiaoxue Lin,&nbsp;Yingyuan Liu,&nbsp;Shengshu Wang,&nbsp;Shengyuan Yu,&nbsp;Zhao Dong","doi":"10.1186/s10194-022-01459-z","DOIUrl":"https://doi.org/10.1186/s10194-022-01459-z","url":null,"abstract":"<p><strong>Background: </strong>There have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors.</p><p><strong>Methods: </strong>The study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES.</p><p><strong>Results: </strong>Among the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005).</p><p><strong>Conclusions: </strong>PAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"92"},"PeriodicalIF":7.4,"publicationDate":"2022-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40559262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galcanezumab in episodic migraine: the phase 3, randomized, double-blind, placebo-controlled PERSIST study.","authors":"Bo Hu,&nbsp;Gang Li,&nbsp;Xiaohong Li,&nbsp;Shan Wu,&nbsp;Tingmin Yu,&nbsp;Xiang Li,&nbsp;Hongru Zhao,&nbsp;Zhihua Jia,&nbsp;Junpeng Zhuang,&nbsp;Shengyuan Yu","doi":"10.1186/s10194-022-01458-0","DOIUrl":"https://doi.org/10.1186/s10194-022-01458-0","url":null,"abstract":"<p><strong>Background: </strong>Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia.</p><p><strong>Methods: </strong>This phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score.</p><p><strong>Results: </strong>In total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo).</p><p><strong>Conclusions: </strong>Galcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier NCT03963232 (PERSIST), registered May 24, 2019.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"90"},"PeriodicalIF":7.4,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40551477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of acute medication use following eptinezumab initiation during a migraine attack: post hoc analysis of the RELIEF study.","authors":"Roger Cady,&nbsp;Richard B Lipton,&nbsp;Dawn C Buse,&nbsp;Mette Krog Josiassen,&nbsp;Annika Lindsten,&nbsp;Anders Ettrup","doi":"10.1186/s10194-022-01463-3","DOIUrl":"https://doi.org/10.1186/s10194-022-01463-3","url":null,"abstract":"<p><strong>Background: </strong>The benefits of preventive treatment on the effectiveness of migraine management have rarely been examined. This post hoc analysis investigated the impact of eptinezumab on the optimization of acute medication effectiveness using the 4-item Migraine Treatment Optimization Questionnaire (mTOQ-4) to measure acute medication optimization over 4 weeks post-infusion.</p><p><strong>Methods: </strong>RELIEF was a 12-week, phase 3, multicenter, parallel-group, double-blind, placebo-controlled clinical trial conducted in patients aged 18-75 years with a ≥ 1-year history of migraine and 4-15 migraine days per month in the 3 months prior to screening. Patients were randomized 1:1 to a 30-min infusion of eptinezumab 100 mg or placebo within 1-6 h of a qualifying migraine attack. The mTOQ-6 and 6-item Headache Impact Test (HIT-6) were administered at screening visit and week 4. From the mTOQ-6, we calculated the mTOQ-4 using the following items: \"2-h pain free,\" \"24-h relief,\" \"able to plan,\" and \"feeling in control\" to measure acute medication optimization.</p><p><strong>Results: </strong>A total of 238 patients received eptinezumab 100 mg and 226 provided week 4 data; 242 received placebo and 232 provided week 4 data. In the eptinezumab arm, the proportion of patients with moderate/maximal optimization increased from 31.4% at baseline to 58.0% (26.6 percentage point increase) at week 4. The corresponding proportions in the placebo group were 40.5% to 50.4% (9.9 percentage point increase). Eptinezumab treatment was associated with numerically larger improvements in HIT-6 at week 4. Relative improvements with eptinezumab vs. placebo from baseline to week 4 in HIT-6 were greater in those with poor treatment optimization at baseline.</p><p><strong>Conclusions: </strong>In comparison with placebo, treatment with eptinezumab was associated with improvements in acute medication optimization as measured by mTOQ and reductions in headache impact, as measured by HIT-6. These benefits were greater in those with poor acute treatment optimization prior to preventive treatment with eptinezumab.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT04152083 .</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"91"},"PeriodicalIF":7.4,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40555592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gradually shifting clinical phenomics in migraine spectrum: a cross-sectional, multicenter study of 5438 patients.","authors":"Ye Ran,&nbsp;Ziming Yin,&nbsp;Yajun Lian,&nbsp;Yanmei Xu,&nbsp;Yajie Li,&nbsp;Jiale Liu,&nbsp;Qun Gu,&nbsp;Fanhong Yan,&nbsp;Zhaoli Ge,&nbsp;Yu Lian,&nbsp;Dongmei Hu,&nbsp;Sufen Chen,&nbsp;Yangyang Wang,&nbsp;Xiaolin Wang,&nbsp;Rongfei Wang,&nbsp;Xiaoyan Chen,&nbsp;Jing Liu,&nbsp;Mingjie Zhang,&nbsp;Xun Han,&nbsp;Wei Xie,&nbsp;Zhe Yu,&nbsp;Ya Cao,&nbsp;Yingji Li,&nbsp;Ke Li,&nbsp;Zhao Dong,&nbsp;Shengyuan Yu","doi":"10.1186/s10194-022-01461-5","DOIUrl":"https://doi.org/10.1186/s10194-022-01461-5","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum.</p><p><strong>Methods: </strong>In this cross-sectional study, 5438 patients from 10 hospitals in China were included: 4651 were diagnosed with migraine without aura (MwoA) and 787 with migraine with aura (MwA). We used a validated standardized electronic survey to collect multidimensional data on headache characteristics and evaluated the similarities and differences between migraine subtypes. To distinguish migraine subtypes, we employed correlational analysis, factor analysis of mixed data (FAMD), and decision tree analysis.</p><p><strong>Results: </strong>Compared to MwA, MwoA had more severe headaches, predominantly affected females, were more easily produced by external factors, and were more likely to have accompanying symptoms and premonitory neck stiffness. Patients with MwA are heterogeneous, according to correlation analysis; FAMD divided the subjects into three clear clusters. The majority of the differences between MwoA and MwA were likewise seen when typical aura with migraine headache (AWM) and typical aura with non-migraine headache (AWNM) were compared. Furthermore, decision trees analysis revealed that the chaotic MwA data reduced the decision tree's accuracy in distinguishing MwoA from MwA, which was significantly increased by splitting MwA into AWM and AWNM.</p><p><strong>Conclusions: </strong>The clinical phenomics of headache phenotype varies gradually from MwoA to AWM and AWNM, and AWM is a mid-state between MwoA and AWNM. We tend to regard migraine as a spectrum disorder, and speculate that different migraine subtypes have different \"predominant regions\" that generate attacks.</p>","PeriodicalId":501630,"journal":{"name":"The Journal of Headache and Pain","volume":" ","pages":"89"},"PeriodicalIF":7.4,"publicationDate":"2022-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40539701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}