{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:37:12Z","timestamp":1784777832792,"version":"3.55.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000882","name":"Brain Research Foundation","doi-asserted-by":"publisher","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}],"id":[{"id":"10.13039\/100000882","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["HRZZ UIP-2019-04-8277"],"award-info":[{"award-number":["HRZZ UIP-2019-04-8277"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1016\/j.ejphar.2023.176279","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T18:54:51Z","timestamp":1702925691000},"page":"176279","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Botulinum toxin type a antinociceptive activity in trigeminal regions involves central transcytosis"],"prefix":"10.1016","volume":"963","author":[{"given":"Dalia","family":"Nemani\u0107","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Mustapi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2441-0031","authenticated-orcid":false,"given":"Ivica","family":"Matak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-833X","authenticated-orcid":false,"given":"Lidija","family":"Bach-Rojecky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"14","key":"10.1016\/j.ejphar.2023.176279_bib1","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1523\/JNEUROSCI.0375-08.2008","article-title":"Long-distance retrograde effects of botulinum neurotoxin A","volume":"28","author":"Antonucci","year":"2008","journal-title":"J. Neurosci."},{"issue":"11","key":"10.1016\/j.ejphar.2023.176279_bib2","doi-asserted-by":"crossref","first-page":"8122","DOI":"10.1016\/S0021-9258(17)37168-5","article-title":"Specific antibodies against the Zn(2+)-binding domain of clostridial neurotoxins restore exocytosis in chromaffin cells treated with tetanus or botulinum A neurotoxin","volume":"269","author":"Bartels","year":"1994","journal-title":"J. Biol. Chem."},{"issue":"7","key":"10.1016\/j.ejphar.2023.176279_bib3","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.celrep.2016.06.104","article-title":"Interneuronal transfer and distal action of tetanus toxin and botulinum neurotoxins A and D in central neurons","volume":"16","author":"Bomba-Warczak","year":"2016","journal-title":"Cell Rep."},{"issue":"4","key":"10.1016\/j.ejphar.2023.176279_bib4","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3344\/kjp.2022.35.4.391","article-title":"The role of botulinum toxin type A related axon transport in neuropathic pain induced by chronic constriction injury","volume":"35","author":"Bu","year":"2022","journal-title":"Korean J Pain"},{"key":"10.1016\/j.ejphar.2023.176279_bib5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.neuroscience.2017.03.049","article-title":"Botulinum neurotoxin type A-cleaved SNAP25 is confined to primary motor neurons and localized on the plasma membrane following intramuscular toxin injection","volume":"352","author":"Cai","year":"2017","journal-title":"Neuroscience"},{"issue":"48","key":"10.1016\/j.ejphar.2023.176279_bib6","doi-asserted-by":"crossref","first-page":"10329","DOI":"10.1523\/JNEUROSCI.0294-18.2018","article-title":"Transynaptic action of botulinum neurotoxin type A at central cholinergic boutons","volume":"38","author":"Caleo","year":"2018","journal-title":"J. Neurosci."},{"issue":"10","key":"10.1016\/j.ejphar.2023.176279_bib7","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1002\/ejp.513","article-title":"Intrathecal administration of botulinum toxin type A improves urinary bladder function and reduces pain in rats with cystitis","volume":"18","author":"Coelho","year":"2014","journal-title":"Eur. J. Pain"},{"issue":"1","key":"10.1016\/j.ejphar.2023.176279_bib8","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-25002-x","article-title":"Intraoperative abobotulinumtoxinA alleviates pain after surgery and improves general wellness in a translational animal model","volume":"12","author":"Cornet","year":"2022","journal-title":"Sci. Rep."},{"issue":"1\u20132","key":"10.1016\/j.ejphar.2023.176279_bib9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.pain.2003.10.008","article-title":"Subcutaneous administration of botulinum toxin A reduces formalin-induced pain","volume":"107","author":"Cui","year":"2004","journal-title":"Pain"},{"issue":"5\u20136","key":"10.1016\/j.ejphar.2023.176279_bib10","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00702-022-02494-5","article-title":"Botulinum toxin therapy: past, present and future developments","volume":"129","author":"Dressler","year":"2022","journal-title":"J. Neural. Transm."},{"key":"10.1016\/j.ejphar.2023.176279_bib11","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuropharm.2013.02.011","article-title":"Involvement of \u03bc-opioid receptors in antinociceptive action of botulinum toxin type A","volume":"70","author":"Drinovac","year":"2013","journal-title":"Neuropharmacology"},{"issue":"6","key":"10.1016\/j.ejphar.2023.176279_bib12","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00702-013-1150-6","article-title":"Association of antinociceptive action of botulinum toxin type A with GABA-A receptor","volume":"121","author":"Drinovac","year":"2014","journal-title":"J. Neural. Transm."},{"issue":"12","key":"10.1016\/j.ejphar.2023.176279_bib13","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00702-016-1605-7","article-title":"Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain","volume":"123","author":"Drinovac Vlah","year":"2016","journal-title":"J. Neural. Transm."},{"issue":"3","key":"10.1016\/j.ejphar.2023.176279_bib14","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/ejp.1146","article-title":"Role of central versus peripheral opioid system in antinociceptive and anti-inflammatory effect of botulinum toxin type A in trigeminal region","volume":"22","author":"Drinovac Vlah","year":"2018","journal-title":"Eur. J. Pain"},{"key":"10.1016\/j.ejphar.2023.176279_bib15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.toxicon.2020.07.014","article-title":"What have we learned about antinociceptive effect of botulinum toxin type A from mirror-image pain models?","volume":"185","author":"Drinovac Vlah","year":"2020","journal-title":"Toxicon"},{"issue":"1","key":"10.1016\/j.ejphar.2023.176279_bib16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029803","article-title":"Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy","volume":"7","author":"Filipovi\u0107","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2023.176279_bib17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.neuroscience.2017.06.004","article-title":"Antinociceptive effect of botulinum toxin A involves alterations in AMPA receptor expression and glutamate release in spinal dorsal horn neurons","volume":"357","author":"Hong","year":"2017","journal-title":"Neuroscience"},{"issue":"2","key":"10.1016\/j.ejphar.2023.176279_bib18","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3109\/08990229009144705","article-title":"Trigeminal projections to contralateral dorsal horn: central extent, peripheral origins, and plasticity","volume":"7","author":"Jacquin","year":"1990","journal-title":"Somatosens. Mot. Res."},{"key":"10.1016\/j.ejphar.2023.176279_bib19","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fneur.2014.00098","article-title":"Spinal central effects of peripherally applied botulinum neurotoxin A in comparison between its subtypes A1 and A2","volume":"5","author":"Koizumi","year":"2014","journal-title":"Front. Neurol."},{"key":"10.1016\/j.ejphar.2023.176279_bib20","series-title":"Botulinum Toxin Treatment in Surgery, Dentistry, and Veterinary Medicine","article-title":"Basic science of pain and botulinum toxin","author":"Lackovi\u0107","year":"2020"},{"issue":"2","key":"10.1016\/j.ejphar.2023.176279_bib21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/bph.13366","article-title":"Activity of botulinum toxin type A in cranial dura: implications for treatment of migraine and other headaches","volume":"173","author":"Lackovi\u0107","year":"2016","journal-title":"Br. J. Pharmacol."},{"issue":"10","key":"10.1016\/j.ejphar.2023.176279_bib22","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3390\/toxins14100704","article-title":"Botulinum neurotoxins beyond neurons: interplay with glial cells","volume":"14","author":"Luvisetto","year":"2022","journal-title":"Toxins"},{"issue":"18","key":"10.1016\/j.ejphar.2023.176279_bib23","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1523\/JNEUROSCI.1897-22.2023","article-title":"Contralateral afferent input to lumbar lamina I neurons as a neural substrate for mirror-image pain","volume":"43","author":"Luz","year":"2023","journal-title":"J. Neurosci."},{"issue":"10","key":"10.1016\/j.ejphar.2023.176279_bib24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0047977","article-title":"The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes","volume":"7","author":"Marinelli","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2023.176279_bib25","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.neuroscience.2011.04.026","article-title":"Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A","volume":"186","author":"Matak","year":"2011","journal-title":"Neuroscience"},{"issue":"8","key":"10.1016\/j.ejphar.2023.176279_bib26","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3390\/toxins11080459","article-title":"Mechanisms of botulinum toxin type A action on pain","volume":"11","author":"Matak","year":"2019","journal-title":"Toxins"},{"issue":"2","key":"10.1016\/j.ejphar.2023.176279_bib27","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.neuint.2012.05.001","article-title":"Botulinum toxin's axonal transport from periphery to the spinal cord","volume":"61","author":"Matak","year":"2012","journal-title":"Neurochem. Int."},{"issue":"8","key":"10.1016\/j.ejphar.2023.176279_bib28","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.pain.2014.04.027","article-title":"Botulinum toxin type A selectivity for certain types of pain is associated with capsaicin-sensitive neurons","volume":"155","author":"Matak","year":"2014","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2023.176279_bib29","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neuroscience.2017.06.040","article-title":"Involvement of substance P in the antinociceptive effect of botulinum toxin type A: evidence from knockout mice","volume":"358","author":"Matak","year":"2017","journal-title":"Neuroscience"},{"issue":"1","key":"10.1016\/j.ejphar.2023.176279_bib30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/bph.14846","article-title":"Evidence for central antispastic effect of botulinum toxin type A","volume":"177","author":"Matak","year":"2020","journal-title":"Br. J. Pharmacol."},{"issue":"Pt 16","key":"10.1016\/j.ejphar.2023.176279_bib31","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1242\/jcs.012211","article-title":"Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential","volume":"120","author":"Meng","year":"2007","journal-title":"J. Cell Sci."},{"issue":"15","key":"10.1016\/j.ejphar.2023.176279_bib32","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.1523\/JNEUROSCI.5490-08.2009","article-title":"Activation of TRPV1 mediates calcitonin gene-related peptide release, which excites trigeminal sensory neurons and is attenuated by a retargeted botulinum toxin with anti-nociceptive potential","volume":"29","author":"Meng","year":"2009","journal-title":"J. Neurosci."},{"key":"10.1016\/j.ejphar.2023.176279_bib33","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3390\/toxins14030161","article-title":"Antinociceptive actions of botulinum toxin A1 on immunogenic hypersensitivity in temporomandibular joint of rats","volume":"14","author":"Mu\u00f1oz-Lora","year":"2022","journal-title":"Toxins"},{"issue":"3","key":"10.1016\/j.ejphar.2023.176279_bib34","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.brainresprot.2005.05.003","article-title":"Peripheral targeting of the trigeminal ganglion via the infraorbital foramen as a therapeutic strategy","volume":"15","author":"Neubert","year":"2005","journal-title":"Brain Res Brain Res Protoc"},{"issue":"7","key":"10.1016\/j.ejphar.2023.176279_bib35","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"18","author":"Percie du Sert","year":"2020","journal-title":"PLoS Biol."},{"issue":"6","key":"10.1016\/j.ejphar.2023.176279_bib37","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1007\/s00204-022-03271-9","article-title":"Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update","volume":"96","author":"Pirazzini","year":"2022","journal-title":"Arch. Toxicol."},{"issue":"2","key":"10.1016\/j.ejphar.2023.176279_bib38","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.neubiorev.2003.12.003","article-title":"The orofacial formalin test","volume":"28","author":"Raboisson","year":"2004","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.ejphar.2023.176279_bib39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.nbd.2015.04.011","article-title":"Botulinum toxin in migraine: role of transport in trigemino-somatic and trigemino-vascular afferents","volume":"79","author":"Ramachandran","year":"2015","journal-title":"Neurobiol. Dis."},{"issue":"44","key":"10.1016\/j.ejphar.2023.176279_bib40","doi-asserted-by":"crossref","first-page":"15650","DOI":"10.1523\/JNEUROSCI.2618-11.2011","article-title":"Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT\/A)","volume":"31","author":"Restani","year":"2011","journal-title":"J. Neurosci."},{"issue":"8","key":"10.1016\/j.ejphar.2023.176279_bib41","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/j.1600-0854.2012.01369.x","article-title":"Botulinum neurotoxin A impairs neurotransmission following retrograde transynaptic transport","volume":"13","author":"Restani","year":"2012","journal-title":"Traffic"},{"issue":"19","key":"10.1016\/j.ejphar.2023.176279_bib42","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231911626","article-title":"Lasting peripheral and central effects of botulinum toxin type A on experimental muscle hypertonia in rats","volume":"23","author":"\u0160o\u0161tari\u0107","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.ejphar.2023.176279_bib43","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0304-3959(92)90003-T","article-title":"The formalin test: an evaluation of the method","volume":"51","author":"Tj\u00f8lsen","year":"1992","journal-title":"Pain"},{"issue":"3","key":"10.1016\/j.ejphar.2023.176279_bib44","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0014-2999(79)90181-X","article-title":"Comparison of the analgesic effects of various opioid peptides by a newly devised intracisternal injection technique in conscious mice","volume":"56","author":"Ueda","year":"1979","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2023.176279_bib45","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1186\/s40064-016-2071-2","article-title":"Central antinociceptive activity of peripherally applied botulinum toxin type A in lab rat model of trigeminal neuralgia","volume":"5","author":"Wu","year":"2016","journal-title":"SpringerPlus"},{"key":"10.1016\/j.ejphar.2023.176279_bib46","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ejphar.2016.09.019","article-title":"Participation of pro- and anti-nociceptive interleukins in botulinum toxin A-induced analgesia in a rat model of neuropathic pain","volume":"791","author":"Zychowska","year":"2016","journal-title":"Eur. J. Pharmacol."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299923007938?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299923007938?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T23:29:44Z","timestamp":1757978984000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299923007938"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":45,"alternative-id":["S0014299923007938"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2023.176279","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Botulinum toxin type a antinociceptive activity in trigeminal regions involves central transcytosis","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2023.176279","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"176279"}}