{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:08:17Z","timestamp":1791065297855,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNPq","award":["304337\/2019-6"],"award-info":[{"award-number":["304337\/2019-6"]}]},{"name":"CNPq","award":["88881.284131\/2018-01"],"award-info":[{"award-number":["88881.284131\/2018-01"]}]},{"name":"CAPES","award":["304337\/2019-6"],"award-info":[{"award-number":["304337\/2019-6"]}]},{"name":"CAPES","award":["88881.284131\/2018-01"],"award-info":[{"award-number":["88881.284131\/2018-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Diabetic neuropathic pain is one of the complications that affect a wide variety of the diabetic population and is often difficult to treat. Only a small number of patients experience pain relief, which usually comes with onerous side effects and low levels of satisfaction. The search for new analgesic drugs is necessary, given the limitations that current drugs present. Combining drugs to treat neuropathic pain has been attracting interest to improve their efficacy compared to single-drug monotherapies while also reducing dose sizes to minimize side effects. The aim of our study was to verify the antinociceptive effect of a synthetic peptide, PnPP-15, alone and combined with pregabalin, in male Swiss diabetic mice using the von Frey method. PnPP-15 is a synthetic peptide derived from PnPP19, a peptide representing a discontinuous epitope of the primary structure of the toxin PnTx2-6 from the venom of the spider Phoneutria nigriventer. The antinociceptive activity of both compounds was dose-dependent and showed synergism, which was verified by isobolographic analysis. Treatment with PnPP-15 did not cause spontaneous or forced motor changes and did not cause any damage or signs of toxicity in the analyzed organs (pancreas, lung, heart, kidney, brain, or liver). In conclusion, PnPP-15 is a great candidate for an analgesic drug against neuropathic pain caused by diabetes and exerts a synergistic effect when combined with pregabalin, allowing for even more efficient treatment.<\/jats:p>","DOI":"10.3390\/toxins15090560","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T10:09:50Z","timestamp":1694081390000},"page":"560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PnPP-15, a Synthetic Peptide Derived from a Toxin from Phoneutria nigriventer Spider Venom, Alleviates Diabetic Neuropathic Pain and Acts Synergistically with Pregabalin in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Xavier Maia","family":"Mariano","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Medicina e Biomedicina da Faculdade Santa Casa de Belo Horizonte, Belo Horizonte 30150-240, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Caroline","family":"de Assis Ferreira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Medicina e Biomedicina da Faculdade Santa Casa de Belo Horizonte, Belo Horizonte 30150-240, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2694-8521","authenticated-orcid":false,"given":"Camila Megale","family":"Almeida-Leite","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0063-4471","authenticated-orcid":false,"given":"C\u00e9lio Jos\u00e9","family":"de Castro Junior","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Medicina e Biomedicina da Faculdade Santa Casa de Belo Horizonte, Belo Horizonte 30150-240, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6185-4032","authenticated-orcid":false,"given":"Maria Elena","family":"de Lima","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Medicina e Biomedicina da Faculdade Santa Casa de Belo Horizonte, Belo Horizonte 30150-240, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3390\/diabetology2020004","article-title":"Diabetes Mellitus: Insights from Epidemiology, Biochemistry, Risk Factors, Diagnosis, Complications and Comprehensive Management","volume":"2","author":"Alam","year":"2021","journal-title":"Diabetology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S2213-8587(22)00218-2","article-title":"Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: A modelling study","volume":"10","author":"Gregory","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The Revised IASP definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2021","journal-title":"Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1152\/physrev.00045.2019","article-title":"Neuropathic pain: From mechanisms to treatment","volume":"101","author":"Finnerup","year":"2021","journal-title":"Physiol. 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