Novel charged sodium and calcium channel inhibitor active against neurogenic inflammation
| العنوان: | Novel charged sodium and calcium channel inhibitor active against neurogenic inflammation |
|---|---|
| المؤلفون: | Thomas Jacquemont, Masakazu Kotoda, Clifford J. Woolf, Laurel M. Heckman, Nick Andrews, Bruce P. Bean, Seungkyu Lee, Han-Xiong Bear Zhang, Michelino Puopolo, Sooyeon Jo, Sébastien Talbot, Maud Pascal, Aakanksha Jain, Jinbo Lee, Pin W. Liu |
| المصدر: | eLife, Vol 8 (2019) eLife |
| بيانات النشر: | eLife Sciences Publications Ltd, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Mouse, Pharmacology, calcitonin gene-related peptide, Sodium Channels, Mice, Calcium Channels, N-Type, 0302 clinical medicine, Sodium channel blocker, Ganglia, Spinal, Biology (General), Nav1.7, Neurogenic inflammation, Voltage-dependent calcium channel, Chemistry, General Neuroscience, Nociceptors, General Medicine, Calcium Channel Blockers, Bupivacaine, Medicine, Neurogenic Inflammation, Cav2.2, Sodium Channel Blockers, Research Article, dorsal root ganglion, QH301-705.5, Sodium, Science, Pain, chemistry.chemical_element, Calcium, Calcitonin gene-related peptide, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Animals, Humans, Calcium Signaling, General Immunology and Microbiology, Calcium channel, Sodium channel, Lidocaine, asthma, Disease Models, Animal, 030104 developmental biology, inflammatory peptide, 030217 neurology & neurosurgery, Neuroscience |
| الوصف: | Voltage-dependent sodium and calcium channels in pain-initiating nociceptor neurons are attractive targets for new analgesics. We made a permanently charged cationic derivative of an N-type calcium channel-inhibitor. Unlike cationic derivatives of local anesthetic sodium channel blockers like QX-314, this cationic compound inhibited N-type calcium channels more effectively with extracellular than intracellular application. Surprisingly, the compound is also a highly effective sodium channel inhibitor when applied extracellularly, producing more potent inhibition than lidocaine or bupivacaine. The charged inhibitor produced potent and long-lasting analgesia in mouse models of incisional wound and inflammatory pain, inhibited release of the neuropeptide calcitonin gene-related peptide (CGRP) from dorsal root ganglion neurons, and reduced inflammation in a mouse model of allergic asthma, which has a strong neurogenic component. The results show that some cationic molecules applied extracellularly can powerfully inhibit both sodium channels and calcium channels, thereby blocking both nociceptor excitability and pro-inflammatory peptide release. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da15a53b3d2fd9e142887faa060738cd https://elifesciences.org/articles/48118 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....da15a53b3d2fd9e142887faa060738cd |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |