Renée M. Girbig Renée M. Girbig Leonie Tix Leonie Tix Anna M. Hartmann Anna M. Hartmann Wenjia Liu Wenjia Liu Pascal Paschenda Pascal Paschenda Alexandru Florea Alexandru Florea Masoud Sadeghzadeh Masoud Sadeghzadeh Karolin Becker Karolin Becker Rupert Palme Rupert Palme Felix M. Mottaghy Felix M. Mottaghy René Tolba René Tolba Fabian Kiessling Fabian Kiessling Anne Rix Anne Rix Jasmin Baier Jasmin Baier Springer 2025 Background 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 σ1 receptor (σ1R) expression, offers a promising approach to better understand underlying mechanisms. Therefore, this study evaluated [¹⁸F]fluspidine positron emission tomography/computed tomography (PET/CT) imaging for detecting σ1R-mediated pain after partial liver resection in rats. Materials and methods 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. Results Despite analgesic treatment, PET/CT and immunohistochemistry revealed elevated σ1R 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. σ1R 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. Conclusion [18F]Fluspidine PET/CT imaging sensitively detected postoperative pain-associated σ1R expression independent of analgesia. This imaging modality could remarkably refine pain monitoring, opening to further studies using different pain and analgesia models. Relevance statement [¹⁸F]Fluspidine PET/CT imaging demonstrates high sensitivity in detecting pain-associated σ1R 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. PDFDocument eng 2026-01-22T13:51:00.217482Z 2025 [18F]fluspidine Pain Measurement Positron Emission Tomography Computed Tomography Rats (Wistar) Sigma-1 receptor 1424907 b application/pdf http://creativecommons.org/licenses/by/4.0/