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The diversion of free radical oxidation products (FROP) into the interstitium causes mast cells to degranulate (Figure 1) (25, 34), thereby provoking inflammation, the activation of nociceptive mechanisms that promote a chronic pain syndrome (28), and pro-fibrotic interactions: here it is worth noting that RXS (including from opiates), bile salts and radiocontrast media evoke a non-IgE anaphylactoid response (25)