{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:08:17Z","timestamp":1791065297937,"version":"4.1.0"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The primary studies have shown that scorpion analgesic peptide N58A has a significant effect on voltage-gated sodium channels (VGSCs) and plays an important role in neuropathic pain. The purpose of this study was to investigate the analgesic effect of N58A on trigeminal neuralgia (TN) and its possible mechanism. The results showed that N58A could significantly increase the threshold of mechanical pain and thermal pain and inhibit the spontaneous asymmetric scratching behavior of rats. Western blotting results showed that N58A could significantly reduce the protein phosphorylation level of ERK1\/2, P38, JNK, and ERK5\/CREB pathways and the expression of Nav1.8 and Nav1.9 proteins in a dose-dependent manner. The changes in current and kinetic characteristics of Nav1.8 and Nav1.9 channels in TG neurons were detected by the whole-cell patch clamp technique. The results showed that N58A significantly decreased the current density of Nav1.8 and Nav1.9 in model rats, and shifted the activation curve to hyperpolarization and the inactivation curve to depolarization. In conclusion, the analgesic effect of N58A on the chronic constriction injury of the infraorbital (IoN-CCI) model rats may be closely related to the regulation of the MAPK pathway and Nav1.8 and Nav1.9 sodium channels.<\/jats:p>","DOI":"10.3390\/toxins13050357","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T12:19:57Z","timestamp":1621253997000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["N58A Exerts Analgesic Effect on Trigeminal Neuralgia by Regulating the MAPK Pathway and Tetrodotoxin-Resistant Sodium Channel"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9883-6900","authenticated-orcid":false,"given":"Chun-Li","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Bo","family":"Song","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition Asbtracts (beta version)","volume":"38","author":"Olesen","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shen, H., Zhou, Q., Pan, X., Li, Z., Wu, J., and Yan, N. 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