{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:34:06Z","timestamp":1787164446149,"version":"build-2736575974"},"reference-count":129,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"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>Peptides from scorpion venom, mainly in species such as Olivierus martensii (formerly Olivierus martensii Karsch, often designated BMK) (BmK) and Tityus serrulatus from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and dialing down inflammation. This review gathers information on their molecular setups: disulfide-bridged types and those without, weighing in at 3 to 10 kilodaltons (kDa). Structural features include motifs stabilized by cysteines. In pain signaling, they block voltage-gated sodium channels (NaV) such as NaV1.7 and NaV1.8; take the BmK analgesic\u2013antitumor peptide (BmK-AGAP) for example. Additionally, scorpion venom heat-resistant peptide (SVHRP) reduces microglia activity. Tests on rodents using formalin injections, acetic acid writhing, and chronic constriction injury (CCI) setups reveal pain relief that depends on dose and stacks up to morphine. Pairings like AGAP with lidocaine decrease the effective dose by half. In terms of safety, therapeutic levels have low-toxicity with a median lethal dose (LD50) over 20 mg\/kg. Issues crop up with immune responses, unintended targets, and differences in venom batches. Clinical information remains thin, so gaps persist. Engineered versions could change the game for neuropathic pain, inflammatory conditions, and cancer-related discomfort. Standardization plus Phase I studies would help move this forward.<\/jats:p>","DOI":"10.3390\/toxins18030120","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:57:13Z","timestamp":1772125033000},"page":"120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stinging Salvation: Harnessing Scorpion Venom Peptides for Revolutionary Pain Relief"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3353-1102","authenticated-orcid":false,"given":"Reza","family":"Mosaddeghi-Heris","sequence":"first","affiliation":[{"name":"Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz 5165990001, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Pandeh","sequence":"additional","affiliation":[{"name":"School of Medicine, Gonabad University of Medical Sciences, Gonabad 9691797852, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Ghorbi","sequence":"additional","affiliation":[{"name":"School of Medicine, Gonabad University of Medical Sciences, Gonabad 9691797852, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-4968","authenticated-orcid":false,"given":"Niloofar","family":"Taheri","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6587-7327","authenticated-orcid":false,"given":"Maedeh","family":"Shariat Zadeh","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2824-8446","authenticated-orcid":false,"given":"Kimia","family":"Bagheri","sequence":"additional","affiliation":[{"name":"Student Research Committee, Babol University of Medical Sciences, Babol 4717647745, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-4128","authenticated-orcid":false,"given":"Paolo","family":"Martelletti","sequence":"additional","affiliation":[{"name":"Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"School of Health, Unitelma Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.15585\/mmwr.mm6736a2","article-title":"Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults\u2014United States, 2016","volume":"67","author":"Dahlhamer","year":"2018","journal-title":"MMWR Morb. 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