{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:47:03Z","timestamp":1782539223534,"version":"3.54.5"},"reference-count":80,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shionogi & Co., Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Neuropathic pain remains difficult to treat because current analgesics often provide insufficient efficacy or dose-limiting adverse effects. Nav1.7 is genetically validated as a key regulator of human pain sensation, but the development of selective small-molecule Nav1.7 inhibitors has been limited by the high similarity among voltage-gated sodium channel subtypes. Methods: We generated monoclonal antibodies selectively targeting Nav1.7, humanized them for therapeutic development, and evaluated their binding, selectivity, functional channel inhibition, systemic analgesic efficacy, and effects on neuronal activity in a rat model of partial sciatic nerve ligation-induced neuropathic pain. Results: The humanized antibodies showed high-affinity and selective binding to Nav1.7 and functionally inhibited the channel in cellular assays. After systemic administration to neuropathic pain model rats, the lead antibody produced robust analgesia lasting at least 96 h. Electrophysiological analyses demonstrated reduced mechanically evoked and spontaneous neuronal activity, and immunohistochemistry showed decreased mechanical stimulus-induced phosphorylation of extracellular signal-regulated kinase in dorsal root ganglion neurons. The antibodies did not impair physiological nociception or motor function under the tested conditions. Conclusions: These findings provide preclinical proof of concept that humanized anti-Nav1.7 antibodies can act as systemically administered, long-acting biologic analgesics for neuropathic pain while preserving normal nociceptive and motor functions. The clinical advancement of S-151128 further supports the translational potential of this modality.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060757","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Systemically Administered Humanized Anti-Nav1.7 Antibody with Long-Lasting Analgesic Activity and Preserved Physiological Nociception"],"prefix":"10.3390","volume":"18","author":[{"given":"Sosuke","family":"Yoneda","sequence":"first","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-1348","authenticated-orcid":false,"given":"Daisuke","family":"Uta","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Yasufuku","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2426-7343","authenticated-orcid":false,"given":"Takuya","family":"Yamane","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"},{"name":"Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saho","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"R&D Supervisory Unit Office, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Takasu","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaya","family":"Izumi","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Fujita","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Nakamori","sequence":"additional","affiliation":[{"name":"Laboratory for Medicinal Chemistry Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"New Business Promotion Department, Shionogi & Co., Ltd., Osaka 530-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Supply Supervisory Unit, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Laboratory for Medicinal Chemistry Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Kasai","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd., Osaka 561-0825, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: An update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2165\/11630030-000000000-00000","article-title":"Heterogeneity of Chronic Pain","volume":"32","author":"Vellucci","year":"2012","journal-title":"Clin. 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