{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:01:42Z","timestamp":1772236902053,"version":"3.50.1"},"posted":{"date-parts":[[2025,10,31]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,29]]},"abstract":"<title>Abstract<\/title>\n                <p>Background: Proinflammatory mediators including COX-2, IL-1\u03b2, IL-6, and TNF-\u03b1, play major roles in the initiation of postsurgical pain. Produced primarily by activated macrophages and microglia, these mediators drive hyperexcitation of nociceptors and promote peripheral and central pain sensitization. Post-transcriptional RNA regulation is a major control point for these mediators, centering around adenine- and uridine-rich elements (ARE) in the 3\u2019 untranslated regions of their mRNA transcripts. The ARE governs RNA stability and translational efficiency through an interaction with ARE-specific RNA binding proteins (AUBP). Tristetraprolin (TTP) is an AUBP that promotes RNA degradation and translational silencing of these mediators to suppress inflammatory responses.\nMethods: Mice with myeloid-specific TTP knockout or TTP knock-in underwent paw incision and were assessed for mechanical allodynia and thermal sensitivity. Molecular and cellular inflammatory responses were monitored at the site of incision, dorsal root ganglia (DRG) and lumbar spinal cord (L-SC) by qPCR, ELISA, immunohistochemistry and\/or flow cytometry.\nResults: TTP deletion exacerbated post-incisional allodynic pain in parallel with increased edema at the site of injury and delayed wound healing but without significant effects on thermal sensitivity. There was an increase in infiltrating macrophages at the incisional site, particularly at the dermal-epidermal junction, in parallel with a robust increase in proinflammatory\/pronociceptive mediators. An enhanced inflammatory response was also detected in the circulation, ipsilateral DRG and L-SC which persisted through post-incisional day 7. Conversely, TTP knock-in mice showed attenuation of allodynic pain and inflammatory responses in skin, DRG, L-SC, and circulation.\nConclusion: TTP plays a critical role in mitigating postsurgical pain by tamping down peripheral, central and systemic inflammatory responses, thus identifying a new target and mechanism for future development of pain therapeutics.<\/p>","DOI":"10.21203\/rs.3.rs-7244841\/v2","type":"posted-content","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:27:39Z","timestamp":1761928059000},"source":"Crossref","is-referenced-by-count":0,"title":["Myeloid-specific Tristetraprolin mitigates postsurgical incisional pain by suppressing proinflammatory responses"],"prefix":"10.21203","author":[{"given":"Abhishek","family":"Guha","sequence":"first","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E","family":"Sorge","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Si","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reed","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohail M","family":"Baig","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Amir","family":"Husain","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacie K.","family":"Totsch","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ava M.","family":"Piper","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perry J.","family":"Blackshear","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences (NIEHS)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"King","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-7244841\/v2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-7244841\/v2.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T16:09:37Z","timestamp":1764605377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-7244841\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-7244841\/v2","relation":{"is-version-of":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7244841\/v1","asserted-by":"subject"}],"is-preprint-of":[{"id-type":"doi","id":"10.1007\/s00011-025-02141-1","asserted-by":"subject"}],"has-version":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7244841\/v1","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2025,10,31]]},"subtype":"preprint"}}