{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:41:06Z","timestamp":1788234066237,"version":"build-2803163510"},"reference-count":40,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH-20-1-0930"],"award-info":[{"award-number":["W81XWH-20-1-0930"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX005937-01"],"award-info":[{"award-number":["BX005937-01"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>\n                    Chronic pain affects nearly 100 million adults in the U.S., yet few novel therapeutics have emerged in recent decades. P2X4 receptor (P2X4R), implicated in pain signaling, represents a promising target. We evaluated a humanized single-chain variable fragment (hscFv) targeting P2X4R for its ability to reduce ATP-induced currents and modulate excitability in human dorsal root ganglion (hDRG) neurons. Voltage-clamp recordings confirmed that human P2X4R (hP2X4R) hscFv significantly reduced ATP-evoked currents in HEK-293T cells expressing human P2X4, likely by relocalization of the receptor to the perinuclear region after hscFv treatment. Immunohistochemistry and transcriptomic analyses demonstrated widespread P2X4R (\n                    <jats:italic>P2RX4<\/jats:italic>\n                    ) expression across hDRG neuronal subtypes in both male and female donors. Current-clamp recordings revealed that hP2X4R hscFv selectively increased action potential (AP) threshold in multi-firing hDRG neurons, without affecting single-firing neurons. Spontaneous activity at rest and depolarizing spontaneous fluctuation (DSF) amplitude were also reduced. Analysis confirmed consistent effects of hP2X4R hscFv on excitability parameters. These findings suggest that hP2X4 hscFv exerts modest but targeted effects on human sensory neurons, supporting its potential as a novel therapeutic for chronic pain.\n                  <\/jats:p>","DOI":"10.1177\/17448069251376200","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T11:46:44Z","timestamp":1756208804000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Humanized anti-P2X4 scFv reduces ATP-induced P2X4 currents and modulates excitability in human DRG neurons"],"prefix":"10.1177","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7939-2886","authenticated-orcid":false,"given":"Nesia A","family":"Zurek","sequence":"first","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"},{"name":"Department of Anesthesia, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W","family":"Shilling","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-9442","authenticated-orcid":false,"given":"Jenna B","family":"Demeter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Ehsanian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleyah E","family":"Goins","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"},{"name":"Department of Anesthesia, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"S\u00e9gu\u00e9la","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June Bryan I","family":"de la Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adinarayana","family":"Kunamneni","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-4834","authenticated-orcid":false,"given":"Karin N","family":"Westlund","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"},{"name":"Biomedical Laboratory Research &amp; Development, New Mexico VA Health Care System, Albuquerque, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-8950","authenticated-orcid":false,"given":"Sascha RA","family":"Alles","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA"},{"name":"Department of Anesthesia, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Dydyk AM Conermann T. Chronic pain. StatPearls Publishing. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK553030\/ (2025 accessed 6 February 2025)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.014399"},{"key":"e_1_3_3_4_2","unstructured":"Vertex Pharmaceuticals. Vertex announces FDA approval of JOURNAVX\u2122 (suzetrigine) a first-in-class treatment for adults with moderate-to-severe acute pain. https:\/\/news.vrtx.com\/news-releases\/news-release-details\/vertex-announces-fda-approval-journavxtm-suzetrigine-first-class (2025 accessed 6 February 2025)."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/56.5.403"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2023.109503"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13957"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2009.09.006"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114205"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-020-09743-w"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.177052"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2024.09.013"},{"key":"e_1_3_3_13_2","first-page":"2247","article-title":"Safety and efficacy of an oral inhibitor of the purinergic receptor P2X7 in adult patients with moderately to severely active Crohn\u2019s disease: a randomized placebo-controlled, double-blind, phase IIa study","volume":"21","author":"Eser A","year":"2015","unstructured":"Eser A, Colombel J-F, Rutgeerts P, Vermeire S, Vogelsang H, Braddock M, Lindsay J, Sands BE, D\u2019Haens G, Danese S. 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Humanized non-opioid composition and therapies for pain management. https:\/\/patents.google.com\/patent\/WO2023114962A1\/en?q=(kunamneni)&inventor=westlund&oq=kunamneni+westlund (2023 accessed 28 February 2025)."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells14130953"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00121"},{"key":"e_1_3_3_29_2","article-title":"Machine learning elucidates electrophysiological properties predictive of multi- and single-firing human and mouse dorsal root ganglia neurons","volume":"24","author":"Zurek NA","year":"2024","unstructured":"Zurek NA, Thiyagarajan S, Ehsanian R, Goins AE, Goyal S, Shilling M, Adams IM, Petersen T. 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Sex differences in pain: a tale of two immune cells. 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