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Neuroinflammatory changes involving neuronal HMGB1 release and astrocytic NF-κB nuclear translocation occur following cortical spreading depolarization (CSD) in wildtype (WT) mice but it is unknown to what extent this occurs in the migraine brain. We therefore investigated in familial hemiplegic migraine type 1 (FHM1) knock-in mice, which express an intrinsic hyperexcitability phenotype, the extent of neuroinflammation without and after CSD. CSD was evoked in one hemisphere by pinprick (single CSD) or topical KCl application (multiple CSDs). Neuroinflammatory (HMGB1, NF-κB) and neuronal activation (pERK) markers were investigated by immunohistochemistry in the brains of WT and FHM1 mutant mice without and after CSD. Effects of NMDA receptor antagonism on basal and CSD-induced neuroinflammatory changes were examined by, respectively, systemically administered MK801 and ifenprodil or topical MK801 application. In FHM1 mutant mice, CSD caused enhanced neuronal HMGB1 release and astrocytic NF-κB nuclear translocation in the cortex and subcortical areas that were equally high in both hemispheres. In WT mice such effects were only pronounced in the hemisphere in which CSD was induced. Neuroinflammatory responses were associated with pERK expression indicating neuronal activation. Upon CSD, contralateral cortical and striatal HMGB1 release was reduced by topical application of MK801 in the hemisphere contralateral to the one in which CSD was induced. This study reveals that neuroinflammatory activation after CSD is widespread and extends to the contralateral hemisphere, particularly in brains of FHM1 mutant mice. Effective blockade of CSD-induced neuroinflammatory responses in the contralateral hemisphere in FHM1 mice by local NMDA receptor antagonism suggests that neuronal hyperexcitability-related neuroinflammation is relevant in migraine pathophysiology, but possibly also other neurological disorders in which spreading depolarization is involved.
Learn More >Pain is a multidimensional experience comprising sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Clinical and research findings have demonstrated a complex interplay between social burdens, individual coping strategies, mood states, psychological disorders, sleep disturbances, masticatory muscle tone, and orofacial musculoskeletal pain. Accordingly, current classification systems for orofacial pain require psychosocial assessments to be an integral part of the multidimensional diagnostic process. Here, we review evidence on how psychosocial and biological factors may generate and perpetuate musculoskeletal orofacial pain. Specifically, we discuss studies investigating a putative causal relationship between stress, bruxism, and pain in the masticatory system. We present findings that attribute brain structures various roles in modulating pain perception and pain-related behavior. We also examine studies investigating how the nervous and immune system on cellular and molecular levels may account for orofacial nociceptive signaling. Furthermore, we review evidence pointing towards associations between orofacial musculoskeletal pain and neuroendocrine imbalances, sleep disturbances, and alterations of the circadian timing system. We conclude with several proposals that may help to alleviate orofacial pain in the future.
Learn More >We sought to investigate emotional reactivity by measuring HRV and pressure pain sensitivity during a passive visualization task in participants with chronic low back pain (CLBP).
Learn More >To review the contemporary issues of healthcare disparities in Headache Medicine with regard to race/ethnicity, socioeconomic status and geography and propose solutions for addressing these disparities.
Learn More >To assess the validity and reliability of the self-administered Visual Aura Rating Scale (VARS) questionnaire using a hospital-based sample in a cross-sectional setting.
Learn More >Migraine shows a significantly higher prevalence in women, especially during reproductive age when menstrual-related hormonal fluctuations represent the most common migraine trigger. Indeed, over 50% of patients report a higher occurrence of migraine attacks during the perimenstrual window. Menstrual migraine attacks are consistently referred to as more disabling, less responsive to symptomatic treatments, longer in duration, and more prone to relapse than non-menstrual migraine attacks. Evidence strongly suggests that estrogen fluctuations are involved in migraine attacks worsening during the perimenstrual window through several mechanisms directly or indirectly involving the CGRP pathway. We aimed to evaluate whether mAbs blocking CGRP-ligand or receptor (CGRP-mAbs) could represent an effective and safe preventive treatment for menstrual migraine attacks in patients with menstrual-related migraine (MRM) with previous treatment failures.
Learn More >Individuals with chronic low back pain (cLBP) frequently report sleep disturbances. Living in a neighborhood characterized by low-socioeconomic status (SES) is associated with a variety of negative health outcomes, including poor sleep. Whether low-neighborhood SES exacerbates sleep disturbances of people with cLBP, relative to pain-free individuals, has not previously been observed. This study compared associations between neighborhood-level SES, pain-status (cLBP vs. pain-free), and daily sleep metrics in 117 adults (cLBP = 82, pain-free = 35). Neighborhood-level SES was gathered from Neighborhood Atlas, which provides a composite measurement of overall neighborhood deprivation (e.g. area deprivation index). Individuals completed home sleep monitoring for 7-consecutive days/nights. Neighborhood SES and pain-status were tested as predictors of actigraphic sleep variables (e.g., sleep efficiency). Analyses revealed neighborhood-level SES and neighborhood-level SES*pain-status interaction significantly impacted objective sleep quality. These findings provide initial support for the negative impact of low neighborhood-level SES and chronic pain on sleep quality.
Learn More >Fremanezumab is a humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide and is approved in Europe for migraine prevention in adults with ≥4 migraine days/month. The Pan-European Real Life (PEARL) study is a 24-month, prospective, observational study of fremanezumab in chronic or episodic migraine. End points include proportion of patients with ≥50% reduction in monthly migraine days during 6 months of treatment (primary); changes in monthly migraine days, disability scores and acute headache medication use; adherence and persistence; and effectiveness in patients switching from another calcitonin gene-related peptide pathway-targeting monoclonal antibody. PEARL is being conducted in approximately 100 centers in 11 European countries (estimated n = 1100). PEARL will generate important real-world data on effectiveness of fremanezumab and treatment patterns in patients with chronic migraine or episodic migraine.
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