{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:29:41Z","timestamp":1768516181672,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,17]]},"group-title":"Neuroscience","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chronic back pain (CBP) is the leading cause of disability affecting 1 in 10 people worldwide. Symptoms are marked by persistent lower back pain, reduced mobility, and heightened cold sensitivity. Here, we utilize a mouse model of CBP induced by injecting urokinase-type plasminogen activator (uPA), a proinflammatory agent in the fibrinolytic pathway, between the L2\/L3 lumbar vertebrae. We identified neuroimmune interactions contributing to uPA-induced CBP (henceforth, uPA-CBP) in mouse dorsal root ganglia (DRG), where nociceptive neurons reside. Flow cytometric data reveal that uPA-CBP increases CD45+CD11b+ cells in the DRG, a population characteristically implicated in other chronic pain models\n                  <jats:sup>1<\/jats:sup>\n                  . Blocking colony stimulating factor 1 receptor (CSF1R) signaling using PLX5622 partially reduced pain, suggesting CD45+CD11b+ macrophage involvement. Whole-cell patch-clamp electrophysiology data indicated DRG neuron hyperexcitability in CBP mice compared to controls. RNA sequencing revealed upregulation of pain- and inflammation-related genes involved in leukocyte migration. Together, these findings underscore the importance of the DRG neuroimmune axis in mediating chronic back pain.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>uPA-CBP induces gait changes, mechanical and thermal sensitivity compared to shams<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>uPA-CBP mice show increased CD45+CD11b+ cells in DRG compared to shams<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>uPA-CBP mice show neuronal excitability in DRG neurons compared to shams<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Pain behaviors are alleviated by pharmacologically blocking CSF1R signaling<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Dysregulation of inflammation- and ion channel-related genes in uPA-CBP DRG<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2024.12.13.628454","type":"posted-content","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T03:40:47Z","timestamp":1734752447000},"source":"Crossref","is-referenced-by-count":0,"title":["Neuroimmune mechanisms of a mouse model of chronic back pain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1834-9994","authenticated-orcid":false,"given":"Aleyah E.","family":"Goins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7939-2886","authenticated-orcid":false,"given":"Nesia A.","family":"Zurek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3720-2371","authenticated-orcid":false,"given":"Cristian O.","family":"Holguin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Gravelle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin","family":"Goyal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4446-8279","authenticated-orcid":false,"given":"Shahani","family":"Noor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-9442","authenticated-orcid":false,"given":"Jenna B.","family":"Demeter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maddy R.","family":"Koch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-7595","authenticated-orcid":false,"given":"June Bryan I.","family":"de la Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-4834","authenticated-orcid":false,"given":"Karin N.","family":"Westlund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-8950","authenticated-orcid":false,"given":"Sascha R.A.","family":"Alles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024122323562630000_2024.12.13.628454v1.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501372112"},{"key":"2024122323562630000_2024.12.13.628454v1.2","unstructured":"Back Pain Consortium (BACPAC) Research Program | NIH HEAL Initiative. n.d. 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