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To examine changes in the occurrence, severity, and symptoms of headache episodes in patients with chronic migraine following eptinezumab treatment.
Learn More >This study investigated the mechanism of action of atogepant, a small-molecule CGRP receptor antagonist recently approved for the preventive treatment of episodic migraine, by assessing its effect on activation of mechanosensitive C- and Aδ-meningeal nociceptors following cortical spreading depression.
Learn More >This meta-analysis compared pressure pain sensitivity in trigeminal, cervical spine and remote pain-free areas between migraine patients and headache-free controls considering diagnosis (episodic versus chronic) and sex. Electronic databases were searched for cross-sectional or prospective case-control studies comparing pressure pain thresholds between migraine and headache-free controls. Data were extracted by two reviewers. The risk of bias and methodological quality was assessed by Newcastle-Ottawa Quality Assessment Scale. Meta-analyses of trigeminal, extra-trigeminal (cervical spine) and remote pain-free areas were compared. Frequency of migraine and sex were taken into account. Mean differences (MD) and random effects were calculated.
Learn More >About 26 million people are living with HIV in sub-Saharan Africa. The DREAM programme in sub-Saharan Africa provides free healthcare for HIV/AIDS and a range of chronic non-communicable diseases. HIV is a risk factor for neurological non-communicable diseases including stroke and epilepsy, which themselves are associated with headache, and HIV may be a direct risk factor for headache. We investigated the prevalence and burden of headache in a HIV+ population in sub-Saharan Africa.
Learn More >Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, has demonstrated efficacy for preventive treatment of episodic and chronic migraine. Since calcitonin gene-related peptide is expressed within the cardio- and cerebrovascular system and may have cardioprotective effects, it is critical to understand the cardio- and cerebrovascular safety of fremanezumab.
Learn More >Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.
Learn More >Sensitization of trigeminal ganglion neurons contributes to primary headache disorders such as migraine, but the specific neuronal and non-neuronal trigeminal subtypes that are involved remain unclear. We thus developed a cell atlas in which human and mouse trigeminal ganglia are transcriptionally and epigenomically profiled at single-cell resolution. These data describe evolutionarily conserved and human-specific gene expression patterns within each trigeminal ganglion cell type, as well as the transcription factors and gene regulatory elements that contribute to cell-type-specific gene expression. We then leveraged these data to identify trigeminal ganglion cell types that are implicated both by human genetic variation associated with migraine and two mouse models of headache. This trigeminal ganglion cell atlas improves our understanding of the cell types, genes, and epigenomic features involved in headache pathophysiology and establishes a rich resource of cell-type-specific molecular features to guide the development of more selective treatments for headache and facial pain.
Learn More >Flexible electronic skin with features that include sensing, processing, and responding to stimuli have transformed human-robot interactions. However, more advanced capabilities, such as human-like self-protection modalities with a sense of pain, sign of injury, and healing, are more challenging. Herein, a novel, flexible, and robust diffusive memristor based on a copolymer of chlorotrifluoroethylene and vinylidene fluoride (FK-800) as an artificial nociceptor (pain sensor) is reported. Devices composed of Ag/FK-800/Pt have outstanding switching endurance >10 cycles, orders of magnitude higher than any other two-terminal polymer/organic memristors in literature (typically 10 -10 cycles). In situ conductive atomic force microscopy is employed to dynamically switch individual filaments, which demonstrates that conductive filaments correlate with polymer grain boundaries and FK-800 has superior morphological stability under repeated switching cycles. It is hypothesized that the high thermal stability and high elasticity of FK-800 contribute to the stability under local Joule heating associated with electrical switching. To mimic biological nociceptors, four signature nociceptive characteristics are demonstrated: threshold triggering, no adaptation, relaxation, and sensitization. Lastly, by integrating a triboelectric generator (artificial mechanoreceptor), memristor (artificial nociceptor), and light emitting diode (artificial bruise), the first bioinspired injury response system capable of sensing pain, showing signs of injury, and healing, is demonstrated.
Learn More >Galanin (GAL) is a nociceptive transmitter or modulator in the trigeminal sensory system. In this study, GAL expression was investigated in the rat dura mater to demonstrate its possible function in headache using immunohistochemical techniques. The cerebral falx and cerebellar dura mater received abundant blood and nerve supply, and were significantly thicker compared to other portions in the cerebral dura mater. GAL-immunoreactivity was expressed by cell and nerve fiber profiles. Presumed macrophages and dendritic cells contained GAL-immunoreactivity, and co-expressed with CD11b-immunoreactivity. Many isolated and perivascular nerve fibers also showed GAL-immunoreactivity. In addition, GAL-immunoreactive nerve fibers were present in the vicinity of macrophages and dendritic cells with either GAL- or ED1-immunoreactivity. GAL-immunoreactive cells and nerve fibers were common in the cerebral falx and cerebellar dura mater and infrequent in other portions. And, GAL-immunoreactive nerve fibers usually co-expressed calcitonin gene-related peptide (CGRP)-immunoreactivity. In the trigeminal ganglion, a substantial proportion of sensory neurons innervating the dura mater contained GAL-immunoreactivity (mean ± SD, 3.4 ± 2.2%), and co-expressed CGRP-immunoreactivity (2.7 ± 2.1%). The present study may suggest that GAL is associated with nociceptive transduction or modulation in the dura mater. GAL also possibly plays a role in the immune mechanism of the dura mater.
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