Do Gadolinium Based Contrast Agents Cause Pain? A Systematic Review

Abstract

Introduction: Gadolinium based contrast agents (GBCAs) are FDA approved compounds used to enhance the quality of magnetic resonance imaging (MRI). These chemicals shorten the T1 and T2 relaxation times of the adjacent hydrogen nuclei, and consequently improve the characterization of different pathologies. More than 30 million doses of GBCAs are administered annually worldwide; however, despite the advantages of these paramagnetic pharmaceuticals, many studies have described high signal intensity in the Globus Pallidus and Dentate Nucleus on unenhanced T1-weighted images, indicating residual gadolinium deposition in the brain parenchyma. Our previous studies have provided the first evidence of Gd deposition in the peripheral nervous system. This evidence of Gadolinium retention in nerves raised significant concerns regarding the toxicity of GBCAs and its long-term impact on the sensory system. This systematic review combines data from multiple papers to study the effect of repeated gadolinium based contrast agents (exposure to GBCAs or gadolinium deposition) on pain development (including central torso pain, arm or leg pain, bone pain, joint pain, pain, chronic pain, myalgia, musculoskeletal system pain, and burning sensation) in patients with normal renal function. Methods: Our search strategy, using Medline, Embase, Cochrane library, Web of science, Google scholar, and Grey Literature, yielded a total of 14 studies, which include 1 randomized controlled trial (RCT), 7 cohort studies, 1 case series and 5 case reports. Only patients with normal renal function were included in this study; those with central or peripheral nervous system lesions were excluded. Data were extracted directly from the selected articles and organized in standardized tables by one investigator and verified by a second. Risk of bias was assessed using Newcastle-Ottawa Quality Assessment Scale criteria for non-randomized studies and Cochrane risk of bias assessment for RCTs. Meta-analysis was not conducted because only one RCT and because of the high risk of bias in all 14 studies. Conclusion: This is the first systematic review of the literature concerning the impact of GBCAs on acute and chronic pain development in patients with normal renal function. Reports of pain induced by GBCAs have been documented in many studies; however, the magnitude of association between GBCAs and pain requires further study.