Dataset Information

Increased GABA+ in People With Migraine, Headache, and Pain Conditions- A Potential Marker of Pain.

ABSTRACT: Treatment outcomes for migraine and other chronic headache and pain conditions typically demonstrate modest results. A greater understanding of underlying pain mechanisms may better inform treatments and improve outcomes. Increased GABA+ has been identified in recent studies of migraine, however, it is unclear if this is present in other headache, and pain conditions. We primarily investigated GABA+ levels in the posterior cingulate gyrus (PCG) of people with migraine, whiplash-headache and low back pain compared to age- and sex-matched controls, GABA+ levels in the anterior cingulate cortex (ACC) and thalamus formed secondary aims. Using a cross-sectional design, we studied people with migraine, whiplash-headache or low back pain (n = 56) and compared them with a pool of age- and sex-matched controls (n = 22). We used spectral-edited magnetic resonance spectroscopy at 3T (MEGA-PRESS) to determine levels of GABA+ in the PCG, ACC and thalamus. PCG GABA+ levels were significantly higher in people with migraine and low back pain compared with controls (eg, migraine 4.89 IU ± 0.62 vs controls 4.62 IU ± 0.38; P = .02). Higher GABA+ levels in the PCG were not unique to migraine and could reflect a mechanism of chronic pain in general. A better understanding of pain at a neurochemical level informs the development of treatments that target aberrant brain neurochemistry to improve patient outcomes. PERSPECTIVE: This study provides insights into the underlying mechanisms of chronic pain. Higher levels of GABA+ in the PCG may reflect an underlying mechanism of chronic headache and pain conditions. This knowledge may help improve patient outcomes through developing treatments that specifically address this aberrant brain neurochemistry.

SUBMITTER: Peek AL

PROVIDER: S-EPMC8935361 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Increased GABA+ in People With Migraine, Headache, and Pain Conditions- A Potential Marker of Pain.

Peek Aimie L AL Leaver Andrew M AM Foster Sheryl S Oeltzschner Georg G Puts Nicolaas A NA Galloway Graham G Sterling Michele M Ng Karl K Refshauge Kathryn K Aguila Maria-Eliza R MR Rebbeck Trudy T

The journal of pain 20210625 12

Treatment outcomes for migraine and other chronic headache and pain conditions typically demonstrate modest results. A greater understanding of underlying pain mechanisms may better inform treatments and improve outcomes. Increased GABA+ has been identified in recent studies of migraine, however, it is unclear if this is present in other headache, and pain conditions. We primarily investigated GABA+ levels in the posterior cingulate gyrus (PCG) of people with migraine, whiplash-headache and low ...[more]

PMID: 34182103

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Project description:Migraine is a multifactorial brain disorder characterized by recurrent disabling headaches and their associated features. Several studies have suggested that these features are related to headache impact, pain intensity, and psychiatric conditions. However, differences in the relationship between each associated feature and headache impact, pain intensity, or psychiatric conditions remain unclear. This study aimed to assess the impact of migraine-associated features on headache impact, pain intensity, and psychiatric conditions in patients with migraine. In this two-centered study, patients with migraine without aura (MwoA) were enrolled to exclude those without headaches and avoid the influence of medication overuse, which is commonly associated with chronic migraine. We used multiple logistic regression to analyze the headache impact, pain intensity, and psychiatric conditions measured using the Headache Impact Test (HIT-6), Visual Analog Scale (VAS), Generalized Anxiety Disorder 7-item scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Patients' likelihood of experiencing symptoms such as nausea, vomiting, photophobia, phonophobia, osmophobia, and allodynia were also recorded. A total of 1103 patients with MwoA were enrolled in this study, and 164 patients were excluded from the study because of missing data. Finally, 939 patients with MwoAs were included. On multiple logistic regression analyses, nausea (odd ratios [OR] 1.87, confidence interval [CI]: 1.37-2.54), vomiting (OR 1.57, CI: 1.11-2.23), photophobia (OR 1.67, CI: 1.18-2.35), and allodynia (OR 1.56, CI: 1.06-2.28) were independent positive predictors of higher HIT-6 scores, and nausea (OR 1.72, CI: 1.22-2.43), vomiting (OR 1.84, CI: 1.29-2.63), phonophobia (OR 1.58, CI: 1.10-2.25), photophobia (OR 1.49, CI: 1.07-2.08), and allodynia (OR 1.81, CI: 1.24-2.66) were independent positive predictors of higher VAS score. Nausea (OR 1.49, CI: 1.09-2.02), phonophobia (OR 2.00, CI: 1.42-2.82), and allodynia (OR 1.81, CI: 1.24-2.63) were independent positive predictors of GAD-7 score. Nausea (OR 1.66, CI: 1.21-2.28), phonophobia (OR 1.49, CI: 1.05-2.11), and allodynia (OR 1.68, CI: 1.16-2.45) were independent positive predictors and vomiting (OR 0.54, CI: 0.37-0.78) was an independent negative predictor of PHQ-9 score. Our results suggest that nausea, vomiting, photophobia, phonophobia, and osmophobia have distinct effects on headache impact, pain intensity, and psychiatric conditions. Understanding these differences can aid in the personalized management of patients with MwoA.

Project description:BACKGROUND:Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity. METHODS:The MAST Study is a prospective, web-based survey that identified US population samples of persons with migraine (using modified International Classification of Headache Disorders-3 beta criteria) and without migraine. Eligible migraine participants averaged ≥1 MHDs over the prior 3 months. Comorbidities "confirmed by a healthcare professional diagnosis" were endorsed by respondents from a list of 21 common cardiovascular, neurologic, psychiatric, sleep, respiratory, dermatologic, pain and medical comorbidities. Multivariable binary logistic regression calculated odds ratios (OR) and 95% confidence intervals for each condition between the two groups adjusting for sociodemographics. Modeling within the migraine cohort assessed rates of conditions as a function of headache pain intensity, MHD frequency, and their combination. RESULTS:Analyses included 15,133 people with migraine (73.0% women, 77.7% White, mean age 43 years) and 77,453 controls (46.4% women, 76.8% White, mean age 52 years). People with migraine were significantly (P < 0.001) more likely to report insomnia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions. Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia). Increasing MHD frequency was associated with increased risk for nearly all conditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever. CONCLUSIONS:In regression models controlled for sociodemographic variables, all conditions studied were reported more often by those with migraine. Whether entered into the models separately or together, headache pain intensity and MHD frequency were associated with increased risk for many conditions. Future work is required to understand the causal sequence of relationships (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of healthcare professional consultation and treatment, and potential detection bias.

Project description:ObjectiveThis experimental study aimed to assess pain sensitivity in low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM), and chronic migraine (CM) patients across the different phases of the migraine cycle.MethodIn this observational, experimental study, clinical characteristics (diary and time from the last/next headache attack), and quantitative sensory testing (QST) (wind-up pain ratio (WUR) and pressure pain threshold (PPT) from the trigeminal area and PPT from the cervical spine) was performed. LFEM, HFEM, and CM were assessed in each of the 4 migraine phases (HFEM and LFEM: interictal, preictal, ictal, and postictal; CM: interictal and ictal) and compared vs. each other's (matched for the phase) and controls.ResultsA total of 56 controls, 105 LFEM, 74 HFEM, and 32 CM were included. No differences in QST parameters were observed between LFEM, HFEM, and CM in any of the phases. During the interictal phase and when comparing with controls the following were found: 1) LFEM had lower trigeminal PPT (p = 0.001) and 2) lower cervical PPT (p = 0.001). No differences were observed between HFEM or CM and healthy controls. During the ictal phase and when comparing with controls the following were found: HFEM and CM had 1) lower trigeminal PPTs (HFEM p = 0.001; CM = p < 0.001), 2) lower cervical PPT s (HFEM p = 0.007; CM p < 0.001), and 3) higher trigeminal WUR (HFEM p = 0.001, CM p = 0.006). No differences were observed between LFEM and healthy controls. During the preictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.007), 2) HFEM had lower trigeminal (p = 0.013) and 3) HFEM had lower cervical (p = .006) PPTs. During the postictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.003), 2) HFEM had lower trigeminal PPT (p = 0.005), and 3) and HFEM had lower cervical (p = 0.007) PPTs.ConclusionThis study suggested that HFEM patients have a sensory profile matching CM better than LFEM. When assessing pain sensitivity in migraine populations, the phase with respects to headache attacks is of utmost importance and can explain the inconsistency in pain sensitivity data reported in the literature.

Project description:Background: Migraine is the most common cause of primary headache in children leading to a decrease in the quality of life. During the last decade, pain catastrophizing construct became a major focus of interest in the study and treatment of pain. Aim of the study: To evaluate pain catastrophizing in episodic and chronic migraine children and adolescents selected in a tertiary headache Center.To test whether the children's pain catastrophizing might be associated (a) with the frequency of attacks and disability (b) with psychopathological aspects (c) with allodynia and total tenderness score as symptom of central sensitization.To test the best discriminating clinical variables and scores between episodic and chronic migraine, including pain catastrophizing. Methods: We conducted a cross sectional observational study on consecutive pediatric patients affected by migraine. We selected 190 headache patients who met the diagnostic criteria for Migraine without aura, Migraine with aura and Chronic migraine. We submitted all children to the Child version of the Pain Catastrophizing Scale (PCS-C), and to the disability scale for migraine (PedMIDAS), general quality of life estimated by children (PedsQL) and parents (PedsQL-P), anxiety and depression (SAFA-A; SAFA-D) scales. We also evaluated headache frequency and the presence and severity of allodynia and pericranial tenderness. Results: No difference was detected in Total Pain Catastrophizing score (PCS-C) between chronic and episodic migraine groups (ANOVA F = 0.59, p = 0.70); the PedMIDAS, the PedsQL-P for physical functioning and the Total Tenderness Score were discriminant variables between episodic and chronic migraine. The PCS-C was not correlated with migraine related disability as expressed by Ped MIDAS, but it was significantly correlated with general low quality of life, allodynia, pericranial tenderness, anxiety, and depression. Conclusion: Pain catastrophizing seems a mental characteristic of a clinical phenotype with psychopathological traits and enhanced expression of central sensitization symptoms. This clinical profile causes general decline in quality of life in the child judgment, with a probable parents' underestimation. In childhood age, it would not be a feature of chronic migraine, but the possibility that it could predict this evolution is consistent and worthy of further prospective evaluation.

Project description:BackgroundThere is an unmet need for a better understanding and management of headache, particularly migraine, beyond specialist centers, which may be facilitated using digital technology.ObjectiveThe objective of this study was to identify where, when, and how people with headache and migraine describe their symptoms and the nonpharmaceutical and medicinal treatments used as indicated on social media.MethodsSocial media sources, including Twitter, web-based forums, blogs, YouTube, and review sites, were searched using a predefined search string related to headache and migraine. The real-time data from social media posts were collected retrospectively for a 1-year period from January 1, 2018, to December 31, 2018 (Japan), or a 2-year period from January 1, 2017, to December 31, 2018 (Germany and France). The data were analyzed after collection, using content analysis and audience profiling.ResultsA total of 3,509,828 social media posts related to headache and migraine were obtained from Japan in 1 year and 146,257 and 306,787 posts from Germany and France, respectively, in 2 years. Among social media sites, Twitter was the most used platform across these countries. Japanese sufferers used specific terminology, such as "tension headaches" or "cluster headaches" (36%), whereas French sufferers even mentioned specific migraine types, such as ocular (7%) and aura (2%). The most detailed posts on headache or migraine were from Germany. The French sufferers explicitly mentioned "headache or migraine attacks" in the "evening (41%) or morning (38%)," whereas Japanese mentioned "morning (48%) or night (27%)" and German sufferers mentioned "evening (22%) or night (41%)." The use of "generic terms" such as medicine, tablet, and pill were prevalent. The most discussed drugs were ibuprofen and naproxen combination (43%) in Japan; ibuprofen (29%) in Germany; and acetylsalicylic acid, paracetamol, and caffeine combination (75%) in France. The top 3 nonpharmaceutical treatments are hydration, caffeinated beverages, and relaxation methods. Of the sufferers, 44% were between 18 and 24 years of age.ConclusionsIn this digital era, social media listening studies present an opportunity to provide unguided, self-reported, sufferers' perceptions in the real world. The generation of social media evidence requires appropriate methodology to translate data into scientific information and relevant medical insights. This social media listening study showed country-specific differences in headache and migraine symptoms experienced and in the times of the day and treatments used. Furthermore, this study highlighted the prevalence of social media usage by younger sufferers compared to that by older sufferers.

Project description:BackgroundThis study aimed to evaluate the effects of Ischemic Compression Myofascial Trigger Points (IC-MTrPs) therapy, applied mainly to the upper trapezius muscle (UTM), on: [1] cervical spine range of motion (CS-ROM), and [2] headache characteristics in migraine patients. Reduced CS-ROM can further contribute to musculoskeletal strain and neurological discomfort in migraine sufferers. The application of IC-MTrPs therapy is of particular interest because it targets these trigger points, potentially normalizing muscle tone and improving local blood flow, which may alleviate pain and restore mobility.DesignA case series employing a repeated-measures design; pilot study.MethodsFifty-three adult female migraine patients were classified into three groups: episodic migraine without aura (MO, n = 31), episodic migraine with aura (MA, n = 15), and chronic migraine (CM, n = 7). Patients underwent seven sessions of IC-MTrPs therapy targeting the shoulder and neck muscles. Assessments were conducted across five sessions: pre-therapy (baseline), post-1st therapy, post-4th therapy, post-7th therapy, and at a 1-month follow-up. Outcome measures included: CS-ROM (assessed using an accelerometer system), subjective headache pain intensity (evaluated via the Visual Analog Scale (VAS)), and calcitonin gene-related peptide (CGRP) concentrations.ResultsCS-ROM for horizontal rotation and forward flexion improved significantly at the 1-month follow-up compared to pre-therapy (baseline) (P < 0.05). Headache intensity during a migraine attacks, as well as headache frequency and duration, significantly decreased at post-7th therapy compared to baseline across all patients (P < 0.05). The highest CGRP concentrations were recorded in CM patients (240.73 ± 79.51 ng/ml). While no significant changes in CGRP levels were observed in patients with MO, CGRP concentration in patients with MA increased significantly at the 1-month follow-up compared to baseline, rising from 151.70 ± 50.85 ng/ml to 176.17 ± 77.21 ng/ml. In patients with CM, the therapy did not result in statistically significant changes in CGRP levels, although reductions in headache frequency and intensity were noted.ConclusionsIC-MTrPs therapy proved effective in increasing CS-ROM and alleviating headache characteristics in all migraine subtypes. However, no significant changes in CGRP levels were observed. Distinct characteristics and responses among different migraine subtypes highlight the need for tailored therapeutic approaches.Trial registrationThe study protocol was retrospectively registered on December 2, 2022, as a clinical trial in the international clinical trial database ClinicalTrials.gov (identifier: NCT05646160).Clinical trial numbernot applicable.

Project description:ObjectiveThis post hoc analysis in patients medically diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) evaluated reductions in the use of acute headache medication (AHM) and sustained changes in the diagnostic status of CM and MOH following eptinezumab treatment in the PROMISE-2 study.BackgroundEptinezumab, a monoclonal antibody that inhibits calcitonin gene-related peptide, is approved in the United States for the preventive treatment of migraine. A previous analysis showed that eptinezumab reduced monthly migraine days and was well tolerated in the subgroup of PROMISE-2 patients diagnosed with both CM and MOH.MethodsThe phase 3, double-blind, placebo-controlled PROMISE-2 study (NCT02974153) randomized adults with CM to eptinezumab 100 mg, 300 mg, or placebo (administered intravenously every 12 weeks for up to two doses). MOH was prospectively diagnosed at screening by trained physicians based on 3 months of medication history and International Classification of Headache Disorders-3β criteria. This post hoc analysis evaluated changes in total and class-specific days of AHM usage, the percentage of patients using AHM at or above MOH diagnostic thresholds, and the percentage of patients experiencing monthly headache and migraine day frequency below diagnostic thresholds for MOH and/or CM.ResultsIn PROMISE-2, 431/1072 (40.2%) patients with CM were diagnosed with MOH (eptinezumab 100 mg, n = 139; 300 mg, n = 147; placebo, n = 145) and were included in this analysis. Total monthly AHM use decreased from 20.6 days/month at baseline to 10.6 days/month over 24 weeks of treatment (49% decrease) with eptinezumab 100 mg, from 20.7 to 10.5 days/month (49% decrease) with eptinezumab 300 mg, and from 19.8 to 14.0 days/month (29% decrease) with placebo. Numerically greater decreases from baseline with eptinezumab were also observed for individual drug classes. In each study month, the percentages of patients who were below MOH thresholds were numerically higher for both eptinezumab doses compared with placebo, as were the percentages of patients experiencing headache and migraine frequency below CM thresholds. Of patients with available data across the entire treatment period, 29.0% (58/200) of patients treated with eptinezumab stopped meeting and remained below diagnostic thresholds for both CM and MOH during Weeks 1-24, as well as 6.3% (6/96) of patients who received placebo.ConclusionsAcross 24 weeks of treatment, eptinezumab reduced AHM use in patients diagnosed with CM and MOH. More than one-fourth (29%) of patients treated with eptinezumab did not meet the diagnostic thresholds for either CM or MOH for the entire treatment period.

Dataset Information

Increased GABA+ in People With Migraine, Headache, and Pain Conditions- A Potential Marker of Pain.

Publications

Increased GABA+ in People With Migraine, Headache, and Pain Conditions- A Potential Marker of Pain.

Similar Datasets

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