{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:04:38Z","timestamp":1778943878339,"version":"3.51.4"},"posted":{"date-parts":[[2024,4,30]]},"group-title":"Pharmacology and Toxicology","reference-count":64,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Persistent pain affects one in five people worldwide, often with severely debilitating consequences. Current treatment options, which can be effective for mild or acute pain, are ill-suited for moderate-to-severe persistent pain, resulting in an urgent need for new therapeutics. In recent years, the somatostatin receptor 4 (SSTR\n                  <jats:sub>4<\/jats:sub>\n                  ), which is expressed in sensory neurons of the peripheral nervous system, has emerged as a promising target for pain relief. However, the presence of several closely related receptors with similar ligand-binding surfaces complicates the design of receptor-specific agonists. In this study, we report the discovery of a potent and selective SSTR\n                  <jats:sub>4<\/jats:sub>\n                  peptide, consomatin Fj1, derived from extensive venom gene datasets from marine cone snails. Consomatin Fj1 is a mimetic of the endogenous hormone somatostatin and contains a minimized binding motif that provides stability and drives peptide selectivity. Peripheral administration of synthetic consomatin Fj1 provided analgesia in mouse models of postoperative and neuropathic pain. Using structure-activity studies, we designed and functionally evaluated several Fj1 analogs, resulting in compounds with improved potency and selectivity. Our findings present a novel avenue for addressing persistent pain through the design of venom-inspired SSTR\n                  <jats:sub>4<\/jats:sub>\n                  -selective pain therapeutics.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Venom peptides from predatory marine mollusks provide new leads for treating peripheral pain conditions through a non-opioid target.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.04.29.591104","type":"posted-content","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T09:08:04Z","timestamp":1714554484000},"source":"Crossref","is-referenced-by-count":2,"title":["Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1019-9239","authenticated-orcid":false,"given":"Walden E.","family":"Bj\u00f8rn-Yoshimoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3971-3107","authenticated-orcid":false,"given":"Iris Bea L.","family":"Ramiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-0375","authenticated-orcid":false,"given":"Thomas Lund","family":"Koch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebbe","family":"Engholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3087-238X","authenticated-orcid":false,"given":"Ho Yan","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasper K.","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn M.","family":"Goddard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrine L.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-4249","authenticated-orcid":false,"given":"Nicholas A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-5335","authenticated-orcid":false,"given":"Laurent F.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth L.","family":"Madsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-5452","authenticated-orcid":false,"given":"Knud J.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amol","family":"Patwardhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1984-2721","authenticated-orcid":false,"given":"Helena","family":"Safavi-Hemami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024050409000714000_2024.04.29.591104v1.1","unstructured":"M. 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