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Ca3.2 T-type calcium channels contribute to CGRP- induced allodynia in a rodent model of experimental migraine.
J Headache Pain
December 2024
Department of Pharmacology, Biological Sciences Sector, Federal University of Parana, Curitiba, PR, Brazil.
Background: Migraine is a painful neurological syndrome characterized by attacks of throbbing headache, of moderate to severe intensity, which is associated with photo- and phono- sensitivity as well as nausea and vomiting. It affects about 15% of the world's population being 2-3 times more prevalent in females. The calcitonin gene-related peptide (CGRP) is a key mediator in the pathophysiology of migraine, and a significant advance in the field has been the development of anti-CGRP therapies.
View Article and Find Full Text PDFC2230, a preferential use- and state-dependent CaV2.2 channel blocker, mitigates pain behaviors across multiple pain models.
J Clin Invest
December 2024
Department of Pharmacology and Therapeutics, College of Pharmacy, University of Florida, Gainesville, United States of America.
Article Synopsis
- - Antagonists like Ziconotide and Gabapentin target CaV2.2 calcium channels to relieve chronic pain, but their clinical use is limited due to issues like narrow therapeutic windows and potential for misuse or side effects.
- - A new compound called C2230 has been identified as a blocker of CaV2.2 channels, showing multiple beneficial effects such as trapping the channel in an inactivated state and specifically targeting pain without affecting other ion channels or motor functions.
- - C2230 effectively reduced pain-like behaviors in various animal models and human neurons, suggesting it could be developed as a new analgesic with a unique binding mechanism that differentiates it from existing treatments.
Effects of transient, persistent, and resurgent sodium currents on excitability and spike regularity in vestibular ganglion neurons.
Front Neurol
November 2024
Department of Neurobiology, University of Chicago, Chicago, IL, United States.
Article Synopsis
- Vestibular afferent neurons are classified into two types based on their spike timing regularity—regular (more excitable with lower thresholds) and irregular (less excitable with higher thresholds)—with distinct expressions of potassium (K) channels influencing these traits.
- Researchers conducted experiments on mouse vestibular ganglion neurons to explore the effects of various sodium (Na) current types (transient, persistent, and resurgent) on spiking behavior, finding that different Na currents affect spike rates and patterns in both regular and irregular neurons.
- Modeling suggested that while increasing transient Na current raises spike rates universally, persistent Na current enhances regularity and rate in sustained neurons but has a minimal effect in transient neurons.
Pharmacologically enabling the degradation of NaV1.8 channels to reduce neuropathic pain.
Pain
November 2024
Program for Neuroscience, University at Buffalo-The State University of New York, Buffalo, NY, United States.
In phase II clinical trials, NaV1.8 channels were identified as viable targets to treat acute pain. Results were modest, however, and NaV1.
View Article and Find Full Text PDFSuccessful treatment of vasospastic angina refractory to various therapies using stenting: A case report.
J Cardiol Cases
September 2024
Division of Cardiology, Showa University Northern Yokohama Hospital, Tsuzuki, Yokohama, Japan.
Unlabelled: We encountered a case of coronary angina refractory to multiple medications, including a calcium channel blocker, nitroglycerin, fasudil (a Rho kinase inhibitor), left stellate ganglion block, thoracic sympathetic ganglion blockade, steroids, and denopamine. During the course of treatment, ventricular tachycardia (VT) occurred due to ST-segment elevation, and an implantable cardioverter-defibrillator was implanted; however, the patient had recurrent VT. A 12‑lead electrocardiogram showed ST elevation localized to leads II, III, and a Vf, and stenting was performed in all main trunks of the right coronary artery.
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