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We studied the color of lighting chosen as comfortable for reading by individuals with migraine and controls. We explored the effects of the chosen color on visual performance.
Learn More >Chronic headaches are poorly diagnosed and managed and can be exacerbated by medication overuse. There is insufficient evidence on the non-pharmacological approaches to helping people living with chronic headaches.
Learn More >Medication overuse headache (MOH) is a chronic pain syndrome that arises from the frequent use of acute antimigraine drugs. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with a possible therapeutic effect in this particular context.
Learn More >The release of the neuropeptide CGRP from the trigeminal ganglion neurons (TGNs) plays a central role in migraine. Whereas CGRP can activate NO release from ganglionic glial cells, NO in turn enhances CGRP release. However, it remains unclear how NO promotes CGRP release. Here, we report that the NO donor SNAP triggered CGRP release from cultured primary TGNs. This event was associated with GSK-3β activation and Akt inactivation. Immunofluorescent staining revealed that GSK-3β primarily located in neurons. Furthermore, GSK-3β inhibition resulted in a marked reduction in expression of CGRP as well as other migraine-related factors, including substance P, cholecystokinin, and prostaglandin E2. Last, exposure to SNAP also activated NF-κB, while NF-κB inhibition prevented the induction of CGRP by SNAP. Interestingly, this event was blocked by GSK-3β inhibition, in association with inhibition of NF-κB/p65 expression and nuclear translocation. Together, these findings argue that NO could stimulate TGNs to release of CGRP as well as other migraine-related factors, likely by activating GSK-3β, providing a novel mechanism underlying a potential feed-forward loop between NO and CGRP in migraine. They also raise a possibility that GSK-3β might act to trigger migraine through activation of NF-κB, suggesting a link between neuroinflammation and migraine.
Learn More >Class B G protein-coupled receptors are highly therapeutically relevant but challenges remain in identifying suitable small-molecule drugs. The calcitonin-like receptor (CLR) in particular is linked to conditions such as migraine, cardiovascular disease, and inflammatory bowel disease. The CLR cannot act as a cell-surface receptor alone but rather must couple to one of three receptor activity-modifying proteins (RAMPs), forming heterodimeric receptors for the peptides adrenomedullin and calcitonin gene-related peptide. These peptides have extended binding sites across their receptors. This is one reason why there are few small-molecule ligands that can modulate these receptors. Here we describe small molecules that are able to positively modulate the signaling of the CLR with all three RAMPs but are not active at the related calcitonin receptor. These compounds were selected from a β-arrestin recruitment screen, coupled with rounds of medicinal chemistry to improve their activity. Translational potential is shown as the compounds can positively modulate cAMP signaling in a vascular cell line model. Binding experiments do not support an extracellular domain binding site; however, molecular modeling reveals potential allosteric binding sites in multiple receptor regions. These are the first small-molecule positive modulators described for the CLR:RAMP complexes.
Learn More >To determine whether Scrambler therapy is an effective, acceptable, and feasible treatment of persistent central neuropathic pain in patients with neuromyelitis optica spectrum disorder (NMOSD) and to explore the effect of Scrambler therapy on co-occurring symptoms.
Learn More >We aimed to assess the efficacy and safety of erenumab, a fully human monoclonal antibody inhibiting the calcitonin gene-related peptide receptor (CGRPr), for the prevention of migraine in a real-life setting.
Learn More >To examine the clinical outcomes of intentional overdoses involving triptans and ergotamines with a retrospective review of the National Poison Data System (NPDS).
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