{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T23:25:28Z","timestamp":1769729128344,"version":"3.49.0"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicon: X"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.toxcx.2020.100045","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T19:36:53Z","timestamp":1591299413000},"page":"100045","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["PnAn13, an antinociceptive synthetic peptide inspired in the Phoneutria nigriventer toxin PnTx4(6\u20131) (\u03b4-Ctenitoxin-Pn1a)"],"prefix":"10.1016","volume":"7","author":[{"given":"Bruna Luiza","family":"Emerich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata Cristina Mendes","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo Andrez","family":"Machado-de-Avila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarbas Magalh\u00e3es","family":"Resende","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor Dimitri G.","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Elena","family":"de Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxcx.2020.100045_bib1","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nn1916","article-title":"Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors","volume":"10","author":"Agarwal","year":"2007","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.toxcx.2020.100045_bib2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.pain.2006.04.001","article-title":"Induction of CB1 cannabinoid receptor by inflammation in primary afferent neurons facilitates antihyperalgesic effect of peripheral CB1 agonist","volume":"124","author":"Amaya","year":"2006","journal-title":"Pain"},{"key":"10.1016\/j.toxcx.2020.100045_bib3","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1074\/jbc.272.6.3315","article-title":"Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes","volume":"272","author":"Bisogno","year":"1997","journal-title":"J. Biol. Chem."},{"issue":"11","key":"10.1016\/j.toxcx.2020.100045_bib4","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.4155\/tde.13.104","article-title":"Basics and recent advances in peptide and protein drug delivery","volume":"4","author":"Bruno","year":"2013","journal-title":"Ther. Deliv."},{"key":"10.1016\/j.toxcx.2020.100045_bib5","series-title":"Fmoc Solid Phase Peptide Synthesis: A Practical Approach","author":"Chan","year":"2000"},{"key":"10.1016\/j.toxcx.2020.100045_bib6","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/nature05413","article-title":"An SCN9A channelopathy causes congenital inability to experience pain","volume":"444","author":"Cox","year":"2006","journal-title":"Nature"},{"issue":"2\u20133","key":"10.1016\/j.toxcx.2020.100045_bib7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0041-0101(00)00129-X","article-title":"Purification and amino acid sequence of a highly insecticidal toxin from the venom of the Brazilian spider Phoneutria nigriventer which inhibits NMDA-evoked currents in rat hippocampal neurones","volume":"39","author":"de Figueiredo","year":"2001","journal-title":"Toxicon"},{"issue":"1","key":"10.1016\/j.toxcx.2020.100045_bib8","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0022-1910(01)00143-3","article-title":"The toxin Tx4(6-1) from the spider Phoneutria nigriventer slows down NA+ current inactivation in insect CNS via binding to receptor site 3","volume":"48","author":"de Lima","year":"2002","journal-title":"J. Insect Physiol."},{"key":"10.1016\/j.toxcx.2020.100045_bib9","series-title":"Biotecnologia Aplicada \u00e0 Sa\u00fade: Fundamentos e Aplica\u00e7\u00f5es","first-page":"539","article-title":"Perspectivas inovadoras para o uso terap\u00eautico de toxinas da aranha \u201carmadeira\u201d Phoneutria nigriventer (Keyserling, 1891) na dor e na disfun\u00e7\u00e3o er\u00e9til","volume":"vol. 1","author":"De Lima","year":"2015"},{"issue":"4","key":"10.1016\/j.toxcx.2020.100045_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/toxins8040106","article-title":"\u03b4-Ctenitoxin-Pn1a, a peptide from Phoneutria nigriventer spider venom, shows antinociceptive effect involving opioid and cannabinoid systems, in rats","volume":"8","author":"Emerich","year":"2016","journal-title":"Toxins"},{"issue":"5","key":"10.1016\/j.toxcx.2020.100045_bib11","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jpain.2017.12.002","article-title":"The involvement of the endocannabinoid system in the peripheral antinociceptive action of ketamine","volume":"19","author":"Ferreira","year":"2018","journal-title":"J. Pain"},{"issue":"1","key":"10.1016\/j.toxcx.2020.100045_bib12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0041-0101(94)00130-Z","article-title":"Purification and amino acid sequence of the insecticidal neurotoxin Tx4(6-1) from the venom of the \u201carmed\u201d spider Phoneutria nigriventer (Keys)","volume":"33","author":"Figueiredo","year":"1995","journal-title":"Toxicon"},{"key":"10.1016\/j.toxcx.2020.100045_bib13","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1111\/bph.13448","article-title":"PnPP-19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidase","volume":"173","author":"Freitas","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.toxcx.2020.100045_bib14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.niox.2017.01.004","article-title":"The synthetic peptide PnPP-19 induces peripheral antinociception via activation of NO\/cGMP\/KATP pathway: role of eNOS and nNOS","volume":"64","author":"Freitas","year":"2017","journal-title":"Nitric Oxide"},{"issue":"6","key":"10.1016\/j.toxcx.2020.100045_bib15","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2174\/187152709789824660","article-title":"The endocannabinoid system and pain","volume":"8","author":"Guindon","year":"2009","journal-title":"CNS Neurol. Disord. - Drug Targets"},{"key":"10.1016\/j.toxcx.2020.100045_bib16","doi-asserted-by":"crossref","first-page":"D653","DOI":"10.1093\/nar\/gkq1058","article-title":"ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures","author":"Herzig","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.toxcx.2020.100045_bib17","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/S0306-4522(99)00220-1","article-title":"Cannabinoid receptors undergo axonal flow in sensory nerves","volume":"92","author":"Hohmann","year":"1999","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxcx.2020.100045_bib18","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S0306-4522(98)00524-7","article-title":"Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: a double-label in situ hybridization study","volume":"90","author":"Hohmann","year":"1999","journal-title":"Neuroscience"},{"issue":"9","key":"10.1016\/j.toxcx.2020.100045_bib19","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1038\/nm.3265","article-title":"Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes","volume":"19","author":"Jourdan","year":"2013","journal-title":"Nat Med. Sep"},{"key":"10.1016\/j.toxcx.2020.100045_bib20","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.toxicon.2008.05.020","article-title":"A rational nomenclature for naming peptide toxins from spiders and other venomous animals","volume":"52","author":"King","year":"2008","journal-title":"Toxicon"},{"key":"10.1016\/j.toxcx.2020.100045_bib21","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/bph.12488","article-title":"Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine","volume":"171","author":"Machado","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.toxcx.2020.100045_bib22","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/3-540-26573-2_10","article-title":"Distribution of cannabinoid receptors in the central and peripheral nervous system","author":"Mackie","year":"2005","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.toxcx.2020.100045_bib23","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.4049\/jimmunol.1403205","article-title":"Endocannabinoid system contributes to liver injury and inflammation by activation of bone marrow-derived monocytes\/macrophages in a CB1-dependent manner","volume":"195","author":"Mai","year":"2015","journal-title":"J. Immunol."},{"key":"10.1016\/j.toxcx.2020.100045_bib24","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/1056-8719(94)90087-6","article-title":"A method to perform direct transcutaneous intrathecal injection in rats","volume":"32","author":"Mestre","year":"1994","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"10.1016\/j.toxcx.2020.100045_bib25","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.2174\/0929867043363884","article-title":"Ziconotide: neuronal calcium channel blocker for treating severe chronic pain","author":"Miljanich","year":"2004","journal-title":"Curr Med Chem, Schiphol (Netherlands)"},{"key":"10.1016\/j.toxcx.2020.100045_bib26","doi-asserted-by":"crossref","DOI":"10.1590\/1678-9199-jvatitd-2019-0022","article-title":"Antinociceptive effect of PnTx4(5-5), a peptide from Phoneutria nigriventer spider venom, in rat models and the involvement of glutamatergic system","volume":"25","author":"Oliveira","year":"2019","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"10.1016\/j.toxcx.2020.100045_bib27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40409-016-0091-6","article-title":"A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems","volume":"22","author":"Pacheco","year":"2016","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"10.1016\/j.toxcx.2020.100045_bib28","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1476-5381.2009.00310.x","article-title":"Central antinociception induced by \u03bc-opioid receptor agonist, but not \u03ba- or \u03b4-, is mediated by canabinoid CB1 receptor","author":"Pacheco","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.toxcx.2020.100045_bib29","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/bjp.2008.175","article-title":"The \u03bc-opioid receptor agonist morphine, but not agonists at delta- or kappa opioid receptors, induces peripheral antinociception mediated by cannabinoid receptors","author":"Pacheco","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.toxcx.2020.100045_bib30","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.biochi.2015.12.019","article-title":"Differential effects of the recombinant toxin PnTx4(5-5) from the spider Phoneutria nigriventer on mammalian and insect sodium channels","volume":"121","author":"Paiva","year":"2016","journal-title":"Biochimie"},{"issue":"151","key":"10.1016\/j.toxcx.2020.100045_bib31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.toxicon.2018.07.008","article-title":"Phoneutria nigriventer venom: a pharmacological treasure","volume":"1","author":"Peigneur","year":"2018","journal-title":"Toxicon"},{"key":"10.1016\/j.toxcx.2020.100045_bib32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1054\/plef.2001.0341","article-title":"Cannabinoid receptors and their ligands","volume":"66","author":"Pertwee","year":"2013","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"issue":"6","key":"10.1016\/j.toxcx.2020.100045_bib33","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/btx661","article-title":"ArachnoServer 3.0: an online resource for automated discovery, analysis and annotation of spider toxins","volume":"34","author":"Pineda","year":"2017","journal-title":"Bioinformatics"},{"key":"10.1016\/j.toxcx.2020.100045_bib34","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0306-4522(03)00333-6","article-title":"The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat","volume":"120","author":"Price","year":"2003","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxcx.2020.100045_bib35","first-page":"409","article-title":"A method for measurement of analgesic activity on inflamed tissues","volume":"111","author":"Randall","year":"1957","journal-title":"Arch. Int. Pharmacody."},{"key":"10.1016\/j.toxcx.2020.100045_bib36","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.jpainsymman.2005.10.003","article-title":"A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain","volume":"31","author":"Rauck","year":"2006","journal-title":"J. Pain Symptom Manag."},{"issue":"2","key":"10.1016\/j.toxcx.2020.100045_bib37","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1213\/ANE.0b013e3182707859","article-title":"CB1 and CB2 cannabinoid receptor agonists induce peripheral antinociception by activation of the endogenous noradrenergic system","volume":"116","author":"Romero","year":"2013","journal-title":"Anesth. Analg."},{"issue":"5","key":"10.1016\/j.toxcx.2020.100045_bib38","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.juro.2015.06.081","article-title":"PnPP-19, a synthetic and non toxic peptide designed from a P. nigriventer toxin, potentiates erectile function via NO\/cGMP","volume":"194","author":"Silva","year":"2015","journal-title":"J. Urol."},{"key":"10.1016\/j.toxcx.2020.100045_bib39","first-page":"67","article-title":"Revision and cladistic analysis of the neotropical spider genus Phoneutria perty, 1833 (araneae, ctenidae), with notes on related cteninae","volume":"12","author":"Sim\u00f3","year":"2001","journal-title":"Bull. Br. Arachnol. Soc."},{"key":"10.1016\/j.toxcx.2020.100045_bib40","first-page":"69","article-title":"Opioid receptors on peripheral sensory neurons","volume":"521","author":"Stein","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.toxcx.2020.100045_bib41","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1006\/bbrc.1996.0156","article-title":"Tissue distribution of opioid receptor gene expression in the rat","volume":"218","author":"Wittert","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.toxcx.2020.100045_bib42","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0304-3959(83)90201-4","article-title":"Ethical guidelines for investigations of experimental pain in conscious animals","volume":"16","author":"Zimmermann","year":"1983","journal-title":"Pain"}],"container-title":["Toxicon: X"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590171020300230?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2590171020300230?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:12:13Z","timestamp":1762917133000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2590171020300230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":42,"alternative-id":["S2590171020300230"],"URL":"https:\/\/doi.org\/10.1016\/j.toxcx.2020.100045","relation":{},"ISSN":["2590-1710"],"issn-type":[{"value":"2590-1710","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PnAn13, an antinociceptive synthetic peptide inspired in the Phoneutria nigriventer toxin PnTx4(6\u20131) (\u03b4-Ctenitoxin-Pn1a)","name":"articletitle","label":"Article Title"},{"value":"Toxicon: X","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxcx.2020.100045","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"100045"}}