Alexander Radbruch, Henning Richter1, Patrick Bücker2, Johannes Berlandi3, Anne Schänzer4, Katerina Deike-Hofmann, Christoph Kleinschnitz5, Heinz-Peter Schlemmer6, Michael Forsting7, Werner Paulus3, Louise F Martin8, Christoph van Thriel9, Uwe Karst2, Astrid Jeibmann3. 1. Diagnostic Imaging Research Unit, Clinic for Diagnostic Imaging, University of Zurich, Zurich, Switzerland. 2. Institute of Inorganic and Analytical Chemistry, University of Münster. 3. Institute of Neuropathology, University Hospital Münster, Münster, Germany. 4. Institute of Neuropathology, Justus Liebig University Giessen, Giessen. 5. Department of Radiology, German Cancer Research Center, Heidelberg. 6. Department of Neuroradiology, University Hospital Bonn, Bonn, Germany. 7. From the Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, Essen. 8. Neurology Clinic, University Hospital Essen, Essen, Germany. 9. Institute of Laboratory Animal Science, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Abstract
OBJECTIVES: In recent years, complaints of patients about burning pain in arms and legs after the injection of gadolinium-based contrast agents (GBCAs) have been reported. In the current study, we investigated changes of small fibers in the epidermis as a potential cause of the patient complaints in a mouse model. METHODS: Six groups of 8 mice were intravenously injected with either a macrocyclic GBCA (gadoteridol, gadoterate meglumine, gadobutrol), a linear GBCA (gadodiamide or gadobenate dimeglumine) (1 mmol/kg body weight), or saline (NaCl 0.9%). Four weeks after injection, animals were euthanized, and footpads were assessed using immunofluorescence staining. Intraepidermal nerve fiber density (IENFD) was calculated, and the median number of terminal axonal swellings (TASs) per IENFD was determined. RESULTS: Nonparametric Wilcoxon signed-rank test revealed significantly lower IENFDs for all GBCAs compared with the control group (P < 0.0001) with the linear GBCAs showing significantly lower IENFDs than the macrocyclic GBCAs (P < 0.0001). The linear GBCAs presented significantly more TAS per IENFD than the control group (P < 0.0001), whereas no significant increase of TAS per IENFD compared with the control group was found for macrocyclic GBCAs (P < 0.237). INTERPRETATION: It is unclear whether or at what dosage the decrease of IENFDs and the increase of TAS per IENFD found in the current animal model will appear in humans and if it translates into clinical symptoms. However, given the highly significant findings of the current study, more research in this field is required.
OBJECTIVES: In recent years, complaints of patients about burning pain in arms and legs after the injection of gadolinium-based contrast agents (GBCAs) have been reported. In the current study, we investigated changes of small fibers in the epidermis as a potential cause of the patient complaints in a mouse model. METHODS: Six groups of 8 mice were intravenously injected with either a macrocyclic GBCA (gadoteridol, gadoterate meglumine, gadobutrol), a linear GBCA (gadodiamide or gadobenate dimeglumine) (1 mmol/kg body weight), or saline (NaCl 0.9%). Four weeks after injection, animals were euthanized, and footpads were assessed using immunofluorescence staining. Intraepidermal nerve fiber density (IENFD) was calculated, and the median number of terminal axonal swellings (TASs) per IENFD was determined. RESULTS: Nonparametric Wilcoxon signed-rank test revealed significantly lower IENFDs for all GBCAs compared with the control group (P < 0.0001) with the linear GBCAs showing significantly lower IENFDs than the macrocyclic GBCAs (P < 0.0001). The linear GBCAs presented significantly more TAS per IENFD than the control group (P < 0.0001), whereas no significant increase of TAS per IENFD compared with the control group was found for macrocyclic GBCAs (P < 0.237). INTERPRETATION: It is unclear whether or at what dosage the decrease of IENFDs and the increase of TAS per IENFD found in the current animal model will appear in humans and if it translates into clinical symptoms. However, given the highly significant findings of the current study, more research in this field is required.
Authors: Elke Anklam; Martin Iain Bahl; Robert Ball; Richard D Beger; Jonathan Cohen; Suzanne Fitzpatrick; Philippe Girard; Blanka Halamoda-Kenzaoui; Denise Hinton; Akihiko Hirose; Arnd Hoeveler; Masamitsu Honma; Marta Hugas; Seichi Ishida; George En Kass; Hajime Kojima; Ira Krefting; Serguei Liachenko; Yan Liu; Shane Masters; Uwe Marx; Timothy McCarthy; Tim Mercer; Anil Patri; Carmen Pelaez; Munir Pirmohamed; Stefan Platz; Alexandre Js Ribeiro; Joseph V Rodricks; Ivan Rusyn; Reza M Salek; Reinhilde Schoonjans; Primal Silva; Clive N Svendsen; Susan Sumner; Kyung Sung; Danilo Tagle; Li Tong; Weida Tong; Janny van den Eijnden-van-Raaij; Neil Vary; Tao Wang; John Waterton; May Wang; Hairuo Wen; David Wishart; Yinyin Yuan; William Slikker Journal: Exp Biol Med (Maywood) Date: 2021-11-16
Authors: Johanna Habermeyer; Janina Boyken; Julia Harrer; Fabio Canneva; Veronika Ratz; Sandra Moceri; Jakob Admard; Nicolas Casadei; Gregor Jost; Tobias Bäuerle; Thomas Frenzel; Christoph Schmitz; Gunnar Schütz; Hubertus Pietsch; Stephan von Hörsten Journal: Sci Rep Date: 2020-12-28 Impact factor: 4.379