{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:07:03Z","timestamp":1789189623822,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR27198099"],"award-info":[{"award-number":["BR27198099"]}]},{"award":["BR27198099"],"award-info":[{"award-number":["BR27198099"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Alpha-latrotoxin (\u03b1-LTX) is the principal vertebrate-specific neurotoxin in widow spider (Latrodectus) venom and a powerful presynaptic secretagogue. Although its receptors, pore-forming activity and stimulation of neurotransmitter release have been studied extensively in central and motor neurons, its relationship to the severe, persistent pain of latrodectism remains poorly understood. This focused review re-examines \u03b1-LTX from a nociceptive perspective. The available evidence supports a model in which \u03b1-LTX binds adhesion G protein-coupled receptor L1 (ADGRL1; latrophilin-1) and neurexin-1\u03b1 on susceptible sensory neurons; inserts a large cation-permeable pore; and promotes membrane depolarisation, calcium entry and release of pain-associated neuropeptides. The transcript-level gene expression of \u03b1-LTX receptor genes in dorsal root ganglion neurons and evidence of toxin-evoked neuropeptide release provide a molecular basis for direct nociceptor activation, although functional validation in defined nociceptor subclasses remains necessary. A comparison with the nociceptive ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) highlights their convergence on calcium-dependent sensory excitation, while distinguishing \u03b1-LTX from toxins that modulate endogenous channels. We propose that the pain of latrodectism is a composite state in which direct nociceptor activation complements muscle spasm and tissue-derived signalling, positioning \u03b1-LTX as a distinctive probe of pain pathways.<\/jats:p>","DOI":"10.3390\/toxins18090393","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:54:19Z","timestamp":1789055659000},"page":"393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-Latrotoxin and Pain: A Nociceptor Perspective on Latrodectism"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-3275","authenticated-orcid":false,"given":"Bazbek","family":"Davletov","sequence":"first","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty A15E3C7, Kazakhstan"},{"name":"Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr","family":"Ignatchenko","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton CB10 1SD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Zhantleuova","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty A15E3C7, Kazakhstan"},{"name":"Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-6280","authenticated-orcid":false,"given":"Rashid A.","family":"Giniatullin","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 80101 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1580\/1080-6032(1997)008[0226:WSELAW]2.3.CO;2","article-title":"Widow spider envenomation (latrodectism): A worldwide problem","volume":"8","author":"Jelinek","year":"1997","journal-title":"Wilderness Environ. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.5694\/j.1326-5377.2003.tb05442.x","article-title":"Latrodectism: A prospective cohort study of bites by formally identified redback spiders","volume":"179","author":"Isbister","year":"2003","journal-title":"Med. J. Aust."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ryan, N.M., Buckley, N.A., and Graudins, A. (2017). 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