{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:42:55Z","timestamp":1785404575979,"version":"3.56.0"},"reference-count":85,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020563","name":"Vicerrector\u00eda de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["C6d. 022343CC"],"award-info":[{"award-number":["C6d. 022343CC"]}],"id":[{"id":"10.13039\/100020563","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["1231042"],"award-info":[{"award-number":["1231042"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1231042"],"award-info":[{"award-number":["1231042"]}],"id":[{"id":"https:\/\/ror.org\/016nafs32","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Center for Nanoscience and Nanotechnology","award":["CIA250002"],"award-info":[{"award-number":["CIA250002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Brain-derived neurotrophic factor (BDNF) is a key mediator of central sensitization and chronic pain through activation of TrkB receptors. Although the Pannexin 1 (Panx1) channel has been implicated in chronic pain, its involvement in BDNF-TrkB signaling remains unclear. Here, we investigated the functional relationship between TrkB activation and Panx1 using a BDNF-induced pain model in rats. Animals received a single intrathecal administration of BDNF, and mechanical nociception was assessed using the Randall\u2013Selitto test. Behavioral analyses were combined with pharmacological interventions, Western blotting, confocal microscopy, YOPRO-1 uptake assays, and ATP quantification in spinal cord tissue. Intrathecal BDNF induced a robust mechanical hyperalgesia that persisted for up to 10 days. Blockade of Panx1 with 10Panx significantly attenuated BDNF-induced hyperalgesia. BDNF increased Src416 phosphorylation, Panx1 phosphorylation, and YOPRO-1 uptake in dorsal horn neurons, indicating enhanced channel activation. These effects were prevented by the TrkB antagonist ANA12, demonstrating that Panx1 acts downstream of BDNF-TrkB signaling. Inhibition of Src-family kinases with PP2 reduced both hyperalgesia and Panx1 activation, supporting a TrkB-Src-Panx1 signaling cascade. Furthermore, BDNF enhanced ATP release from spinal cord slices, an effect abolished by ANA12, PP2, and 10Panx. Together, these findings identify Panx1 as a downstream effector engaged by BDNF-TrkB signaling during the onset of mechanical hyperalgesia. While persistent TrkB activation appears to be required for the prolonged nociceptive state, the Src family kinase-Panx1 pathway contributes primarily to the early phase of BDNF-induced sensitization.<\/jats:p>","DOI":"10.3390\/ijms27146510","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:48:28Z","timestamp":1784717308000},"page":"6510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BDNF-TrkB Signaling Engages a Src Family Kinase-Pannexin 1 Pathway During the Onset of Sustained Mechanical Hyperalgesia"],"prefix":"10.3390","volume":"27","author":[{"given":"Jonathan","family":"Ar\u00e1nguiz Barrera","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"},{"name":"Kinesiology School, Faculty of Medicine, University of Valpara\u00edso, Valpara\u00edso 2340000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mar\u00eda","family":"Moreira-Banuth","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Zepeda-Morales","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-7150","authenticated-orcid":false,"given":"Mar\u00eda","family":"Triolo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas I.","family":"Oneto","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5143-4278","authenticated-orcid":false,"given":"David","family":"Bravo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pablo","family":"Huidobro-Toro","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Ver\u00f3nica","family":"Donoso","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Noseda","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215-5400, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Pelissier","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cl\u00ednica Alemana University del Desarrollo, Santiago de Chile 7610315, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-0119","authenticated-orcid":false,"given":"Luis","family":"Constandil","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-4530","authenticated-orcid":false,"given":"Jeffri S.","family":"Retamal","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Alameda Libertador Bernardo O\u2019Higgins 3363, Santiago 9170022, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/pm\/pnx336","article-title":"Scope and Nature of Pain- and Analgesia-Related Content of the United States Medical Licensing Examination (USMLE)","volume":"19","author":"Fishman","year":"2018","journal-title":"Pain Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Goldberg, D.S. 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