Diagnostic Imaging Research Unit, Clinic for Diagnostic Imaging, University of Zurich, Zurich, Switzerland.
Institute of Inorganic and Analytical Chemistry, University of Münster.
Invest Radiol. 2020 Aug;55(8):473-480. doi: 10.1097/RLI.0000000000000677.
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.
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.
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).
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.
近年来，有患者抱怨在注射钆基造影剂（GBCA）后出现手臂和腿部灼烧样疼痛。在本研究中，我们通过建立小鼠模型，研究表皮小纤维的变化是否是引起患者上述症状的潜在原因。
6 组 8 只小鼠分别静脉注射大环 GBCA（钆特醇、钆喷酸葡胺、钆贝葡胺）、线性 GBCA（钆双胺或钆贝酸二葡甲胺）（1mmol/kg 体重）或生理盐水（0.9%NaCl）。注射 4 周后处死动物，采用免疫荧光染色法检测足垫。计算表皮内神经纤维密度（IENFD），并确定每单位 IENFD 的末端轴突膨体（TAS）的中位数。
非参数 Wilcoxon 符号秩检验显示，与对照组相比，所有 GBCA 的 IENFD 均显著降低（P<0.0001），线性 GBCA 的 IENFD 显著低于大环 GBCA（P<0.0001）。线性 GBCA 每单位 IENFD 的 TAS 明显多于对照组（P<0.0001），而大环 GBCA 与对照组相比，TAS 每单位 IENFD 无明显增加（P<0.237）。
目前的动物模型中发现的 IENFD 减少和 TAS 每单位 IENFD 增加是否会出现在人类身上，以及是否会转化为临床症状，目前尚不清楚。然而，鉴于本研究的高度显著发现，需要在该领域开展更多的研究。
