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Common analgesic drugs are difficult for achieving the desired analgesic effect. Syb-prII-1 is a \u03b2-type scorpion neurotoxin isolated from the scorpion venom of Buthus martensi Karsch (BmK). It has an important influence on the voltage-gated sodium channel (VGSCs), especially closely related to Nav1.8 and Nav1.9. To explore whether Syb-prII-1 has a good analgesic effect on TN, we established the Sprague Dawley (SD) rats\u2019 chronic constriction injury of the infraorbital nerve (IoN-CCI) model. Behavioral, electrophysiological, Western blot, and other methods were used to verify the model. It was found that Syb-prII-1 could significantly relieve the pain behavior of IoN-CCI rats. After Syb-prII-1 was given, the phosphorylation level of the mitogen-activated protein kinases (MAPKs) pathway showed a dose-dependent decrease after IoN-CCI injury. Moreover, Syb-prII-1(4.0 mg\/kg) could significantly change the steady-state activation and inactivation curves of Nav1.8. The steady-state activation and inactivation curves of Nav1.9 were similar to those of Nav1.8, but there was no significant difference. It was speculated that it might play an auxiliary role. The binding mode, critical residues, and specific interaction type of Syb-prII-1 and VSD2rNav1.8 were clarified with computational simulation methods. Our results indicated that Syb-prII-1 could provide a potential treatment for TN by acting on the Nav1.8 target.<\/jats:p>","DOI":"10.3390\/ijms23137065","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"7065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Scorpion Neurotoxin Syb-prII-1 Exerts Analgesic Effect through Nav1.8 Channel and MAPKs Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Fei","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, 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":"Chunli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,25]]},"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","volume":"38","author":"Arnold","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1212\/WNL.0000000000002840","article-title":"Trigeminal neuralgia: New classification and diagnostic grading for practice and research","volume":"87","author":"Cruccu","year":"2016","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.brainresbull.2017.07.005","article-title":"Inhibitory effects of tetramethylpyrazine on pain transmission of trigeminal neuralgia in CCI-ION rats","volume":"134","author":"Wei","year":"2017","journal-title":"Brain Res. 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