Anxiety and delayed adverse reactions to iodinated contrast media used in radiological examinations

Radiological examinations using iodinated contrast media (ICM) may cause immediate and delayed adverse reactions (ARs). The delayed ARs occur within several days, mainly 1 day, after the examination. Symptoms include fever, fatigue and cutaneous manifestations, The precise pathogenesis of delayed ARs is unclear. We would propose the importance of mental stress or anxiety in the pathogenesis of delayed ARs. A computed tomography (CT) or an angiography can cause anxiety in a patient. Anxiety provokes an increased release of neuropeptides, such as substance P (sub-P) from the peripheral nerve endings. Sub-P is known to stimulate mast cells to release histamins, and subsequently produce inflammatory cytokines, ICM are also known to have a direct effect on increasing the susceptibilities of mast cells. Vasoactive and inflammatory mediators from mast cells dually stimulated by neuropeptides and ICM can cause the symptoms of delayed ARs. Our study revealed that plasma sub-P level was raised after contrast-enhanced CTexaminations (n = 16, p < 0.95, t test). We also carried out an animal experiment using neonatal mice. We found that an injection of sub-P into the skin caused an erythematous reaction in the animals, which was enhanced by the intraperitoneal administration of ICM. These results partially support our hypothesis.