Lipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons.

Transient Receptor Potential (TRP) ion channels like Vanilloid 1 (TRPV1) and Melastatin 3 (TRPM3) are nonselective cation channels expressed in primary sensory neurons and peripheral nerve endings, which are located in cholesterol- and sphingolipid-rich membrane lipid raft regions and have important roles in pain processing. Besides TRP ion channels a wide variety of voltage-gated ion channels were also described in the membrane raft regions of neuronal cells. Here we investigated the effects of lipid raft disruption by methyl-beta-cyclodextrin (MCD) and sphingomyelinase (SMase) on TRPV1, TRPM3 and voltage-gated L-type Ca channel activation in cultured trigeminal neurons and sensory nerve terminals of the trachea.

Novel multitarget analgesic candidate SZV-1287 demonstrates potential disease-modifying effects in the monoiodoacetate-induced osteoarthritis mouse model.

Introduction: Monoiodoacetate (MIA)-induced osteoarthritis (OA) is the most commonly used rodent model for testing anti-OA drug candidates. Herein, we investigated the effects of our patented multitarget drug candidate SZV-1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime) that is currently under clinical development for neuropathic pain and characterized the mouse model through complex functional, imaging, and morphological techniques.

Methods: Knee OA was induced by intraarticular MIA injection (0.

Topiramate inhibits adjuvant-induced chronic orofacial inflammatory allodynia in the rat.

Chronic orofacial pain disorders are common debilitating conditions, affecting the trigeminal system. Its underlying pathophysiological mechanisms are still unclear and the therapy is often unsatisfactory, therefore, preclinical models are crucial to identify the key mediators and novel treatment options. Complete Freund's adjuvant (CFA)-induced orofacial inflammatory allodynia/hyperalgesia is commonly used in rodents, but it has not been validated with currently used drugs.

Plasma Somatostatin Levels Are Lower in Patients with Coronary Stenosis and Significantly Increase after Stent Implantation.

: Stimulated capsaicin-sensitive peptidergic sensory nerves release somatostatin (SST), which has systemic anti-inflammatory and analgesic effects, correlating with the severity of tissue injury. Previous studies suggest that SST release into the systemic circulation is likely to serve as a protective mechanism during thoracic and orthopedic surgeries, scoliosis operations, and septic conditions, all involving significant tissue damage, pain, and inflammation. In a severe systemic inflammation rat model, SST released from sensory nerves into the bloodstream enhanced innate defense, reducing mortality.

The PARP inhibitor rucaparib blocks SARS-CoV-2 virus binding to cells and the immune reaction in models of COVID-19.

Background And Purpose: To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19.

Experimental Approach: The effects of PARP inhibitors on virus uptake were assessed in cell-based experiments using multiple variants of SARS-CoV-2.