[¹⁸F]Fluspidine PET/CT imaging to assess postoperative pain-associated σ1 receptor expression in female rats under analgesia

Title (eng)
[¹⁸F]Fluspidine PET/CT imaging to assess postoperative pain-associated σ1 receptor expression in female rats under analgesia
Author
Renée M. Girbig
Author
Leonie Tix
Author
Anna M. Hartmann
Author
Wenjia Liu
Author
Pascal Paschenda
Author
Alexandru Florea
Author
Masoud Sadeghzadeh
Author
Karolin Becker
Author
Rupert Palme
Author
Felix M. Mottaghy
Author
René Tolba
Author
Fabian Kiessling
Author
Anne Rix
Author
Jasmin Baier
Abstract (eng)
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.
Keywords (eng)
[18F]fluspidinePain MeasurementPositron Emission Tomography Computed TomographyRats (Wistar)Sigma-1 receptor
Type (eng)
journal article
Language
[eng]
Persistent identifier
https://phaidra.vetmeduni.ac.at/o:4777
DOI
10.1186/s41747-025-00646-2
Is in series
Title (eng)
European Radiology Experimental
Volume
9
Issue
1
ISSN
2509-9280
Issued
2025
Number of pages
11
Publication
Springer
Version type (eng)
version of record (published version)
Date issued
2025
Access rights (eng)
open access
License
CC BY 4.0 International
Rights statement (eng)
© The Author(s) 2025