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Migraine is often accompanied with chronic tinnitus that will affect the cerebral blood flow (CBF) and exacerbate the tinnitus distress. However, the potential relationship between migraine and tinnitus remains unclear. This study will investigate whether aberrant CBF patterns exist in migraine patients with tinnitus and examine the influence of migraine on CBF alterations in chronic tinnitus.
Learn More >Study of intraepidermal nerve fiber density (IENFD) by skin biopsy represents a promising tool in the evaluation of patients with ATTRv polyneuropathy (ATTRv-PN). Herein, we retrospectively analyze intraepidermal innervation and quantitative sensory test (QST) data from an Italian cohort of Italian ATTRv-PN patients and asymptomatic carriers aimed to provide insights into early nerve pathological and functional changes in this disease.
Learn More >The calcitonin gene-related peptide (CGRP) system has emerged as a key pharmacological target for the treatment of migraine. However, some individuals who suffer from migraine have low or no response to anti-CGRP or other treatments, suggesting the need for additional clinical targets. CGRP belongs to the calcitonin family of peptides, including calcitonin, amylin, adrenomedullin and adrenomedullin 2. These peptides display a range of pro- and anti-nociceptive actions, including in primary headache conditions such as migraine. Calcitonin family peptides also show expression at sites relevant to migraine and pain. This suggests that calcitonin family peptides and their receptors, beyond CGRP, may be therapeutically useful in the treatment of migraine and other pain disorders. This review considers the localisation of the calcitonin family in peripheral pain pathways and discusses how they may contribute to migraine and pain.
Learn More >There is an unmet need for new efficacious, well-tolerated, acute treatments for migraine in adolescents. Remote electrical neuromodulation (REN) is a novel, non-pharmacological treatment, that provides significant symptom relief with good tolerability. The current post-hoc analysis compared the efficacy of REN to that of standard-care medications, for the acute treatment of migraine in adolescents.
Learn More >Recently, the FDA approved ubrogepant and rimegepant as oral drugs to treat migraines by targeting the calcitonin-gene related peptide receptor (CGRPR). Unfortunately, there is no high-resolution complex structure with these two drugs; thus the detailed interaction between drugs and the receptor remains elusive. This study uses molecular docking and molecular dynamics simulation to model the drug-receptor complex and analyze their binding interactions at a molecular level. The complex crystal structure (3N7R) of the gepant drugs' predecessor, olcegepant, was used for our molecular docking of the two drugs and served as a control system. The three systems, with ubrogepant, rimegepant, and crystal olcegepant, were subject to 3 × 1000 ns molecular dynamics simulations and followed by the simulation interaction diagram (SID), structural clustering, and MM-GBSA binding energy analyses. Our MD data revealed that olcegepant binds most strongly to the CGRPR, followed by ubrogepant and then rimegepant, largely due to changes in hydrophobic and electrostatic interactions. The order of our MM-GBSA binding energies of these three compounds is consistent with their experimental IC values. SID analysis revealed the pharmacophore of the gepant class to be the dihydroquinazolinone group derivative. Subtle differences in interaction profile have been noted, including interactions with the W74 and W72 residues. The ubrogepant and rimegepant both contact A70 and M42 of the receptor, while olcegepant does not. The results of this study elucidate the interactions in the binding pocket of CGRP receptor and can assist in further development for orally available antagonists of the CGRP receptor.
Learn More >Neuropathic pain is one of the foremost adverse effects that worsens quality of life for patients undergoing an antiretroviral treatment. Currently, there are no effective analgesics for relieving it; thus, there is an urgent need to develop novel treatments for neuropathic pain. Previously, we described and validated F11 cells as a model of DRG (dorsal root ganglia) neurons. In the current work, we employed F11 cells to identify regulators of antiretroviral-induced neuropathic pain combining functional and transcriptomic analysis. The antiretroviral zalcitabine (ddC) increased the excitability of differentiated F11 cells associated with calcium signaling without morphological changes in the neuronal phenotype, mimicking the observed increase of painful signaling in patients suffering from antiretroviral-induced neuropathic pain. Employing RNA sequencing, we observed that zalcitabine treatment upregulated genes related with oxidative stress and calcium homeostasis. The functional impact of the transcriptomic changes was explored, finding that the exposure to zalcitabine significantly increased intracellular oxidative stress and reduced store-operated calcium entry (SOCE). Because the functional and transcriptomic evidence points toward fundamental changes in calcium signaling and oxidative stress upon zalcitabine exposure, we identified that NAD(P)H quinone dehydrogenase and the sarcoplasmic/endoplasmic reticulum calcium ATPase 3 were involved in zalcitabine-induced hyperexcitability of F11 cells. Overexpression of those genes increases the calcium-elicited hyperexcitability response and reduces SOCE, as well as increases intracellular ROS levels. These data do not only mimic the effects of zalcitabine but also highlight the relevance of oxidative stress and of calcium-mediated signaling in antiretroviral-induced hyperexcitability of sensory neurons, shedding light on new therapeutic targets for antiviral-induced neuropathic pain.
Learn More >To identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways.
Learn More >Recent evidence suggests that pain dampens attentional processes. However, much of this work has been based on higher-order attentional tasks that involve only spatial attention. Other aspects of the process through which pain engages and holds attention are relatively understudied, in particular, temporal attention. The present set of studies explored how naturally occurring pain (i.e., acute headache) and pain-valenced stimuli affect ability to recall the second of two targets presented in rapid succession. Across both experiments participants were required to indicate the presence of a predefined probe (T2) and, in the dual task, identify a target (T1). The probe (T2) was placed in three different temporal proximities (ranging from 70ms to 1000ms) following presentation of the target (T1). In experiment 1, thirty-six participants completed a task that comprised a rapid stream of letters. Experiment 2 manipulated the threat value, and the complexity, of the stimuli by replacing letters with words. In the dual task condition, T1 was a word from one of four affect categories (neutral, positive, negative, pain). Being in acute pain reduced the accuracy of identification. This reduction in performance occurred regardless of the temporal positioning of the probe consistent with previous work that suggests pain has an overall dampening effect. Further, when the affect category of the word was pain-related, T2 accuracy performance was negatively affected. These findings add to the previous evidence that pain has a general dampening effect on attention and that pain-related stimuli are difficult to disengage from.
Learn More >To investigate the current headache medicine education paradigm in allopathic and osteopathic medical schools in the United States and Canada.
Learn More >Chronic overlapping pain conditions (COPCs) represent a co-aggregation of widespread pain disorders. We characterized differences in physical and psychosocial functioning in patients with chronic migraine (CM) and those with CM and COPCs.
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