{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T17:08:05Z","timestamp":1762276085903,"version":"build-2065373602"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["321137804"],"award-info":[{"award-number":["321137804"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol Exp"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pain assessment in animal models is challenging, as behavioral tests often lack sensitivity. Particularly under analgesia, it is unclear whether pain occurs without medication. Imaging of pain-associated pathways, such as \u03c31 receptor (\u03c31R) expression, offers a promising approach to better understand underlying mechanisms. Therefore, this study evaluated [\u00b9\u2078F]fluspidine positron emission tomography\/computed tomography (PET\/CT) imaging for detecting \u03c31R-mediated pain after partial liver resection in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Postoperative pain was assessed in eighteen female Wistar rats undergoing skin incision or partial liver resection. Nine untreated rats served as controls. Carprofen was administered for three consecutive days after surgery. PET\/CT imaging was performed on postoperative days 1, 4, and 7. At each time point, organs and incision sites of three animals were harvested for histological analysis. Postoperative pain and welfare were monitored by observational score sheets, the Open Field test, Rat Grimace Scale, Von Frey test, fecal corticosterone metabolites, and hemograms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Despite analgesic treatment, PET\/CT and immunohistochemistry revealed elevated \u03c31R expression at the abdominal incision site on day 1 after partial liver resection in comparison to the other groups, likely due to the additional peritoneal opening. \u03c31R expression normalized by day 4. No behavioral indicators of pain or distress were observed, though mechanical hypersensitivity was detected on day 4 in all groups, likely due to carprofen side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]Fluspidine PET\/CT imaging sensitively detected postoperative pain-associated \u03c31R expression independent of analgesia. This imaging modality could remarkably refine pain monitoring, opening to further studies using different pain and analgesia models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance statement<\/jats:title>\n                    <jats:p>[\u00b9\u2078F]Fluspidine PET\/CT imaging demonstrates high sensitivity in detecting pain-associated \u03c31R upregulation despite non-steroidal anti-inflammatory drug administration. This approach offers valuable insights for refining pain assessment, improving severity grading, and enhancing the reliability and translational value of preclinical pain models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            PET\/CT imaging with [\n                            <jats:sup>18<\/jats:sup>\n                            F]fluspidine sensitively detects pain-associated \u03c31R expression post-liver resection.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Necessary analgesia interferes with some behavioral tests, limiting their reliability for pain assessment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            [\n                            <jats:sup>18<\/jats:sup>\n                            F]Fluspidine detects peripheral \u03c31R upregulation despite non-steroidal anti-inflammatory drug analgesia.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Imaging pain-associated receptors provides valuable insights for refining preclinical pain monitoring.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s41747-025-00646-2","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T17:03:21Z","timestamp":1762275801000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["[\u00b9\u2078F]Fluspidine PET\/CT imaging to assess postoperative pain-associated \u03c31 receptor expression in female rats under analgesia"],"prefix":"10.1186","volume":"9","author":[{"given":"Ren\u00e9e M.","family":"Girbig","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Rix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin","family":"Baier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Tix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Paschenda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandru","family":"Florea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masoud","family":"Sadeghzadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolin","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupert","family":"Palme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix M.","family":"Mottaghy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Tolba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7341-0399","authenticated-orcid":false,"given":"Fabian","family":"Kiessling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"646_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1258\/la.2010.010031","volume":"45","author":"P Hawkins","year":"2011","unstructured":"Hawkins P, Morton DB, Burman O et al (2011) A guide to defining and implementing protocols for the welfare assessment of laboratory animals: eleventh report of the BVAAWF\/FRAME\/RSPCA\/UFAW Joint Working Group on Refinement. 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All animals in the present study received human care according to the principles of the \u201cGuide for the Care and Use of Laboratory Animals\u201d (8th edition, NIH Publication, 2011, USA).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"FMM is a medical advisor and consultant for Advanced Accelerator Applications (AAA) GmbH\/Novartis, Telix Pharmaceuticals, and CURIUM TM, and has recently received institutional grants from NanoMab Technology Ltd., Radiopharm Ltd., Siemens Healthcare, and GE Precision Healthcare LLC. FK is a member of the Scientific Editorial Board of European Radiology Experimental (section editor: Cell\/tissue, animal, digital models of human physiopathology) and, as such, did not participate in the selection or review processes for this article. The other authors have no conflicts of interest to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"108"}}