Evidence that toluene diisocyanate activates the efferent function of capsaicin-sensitive primary afferents

Isocyanates are an important cause of occupational asthma. The mechanism of isocyanate-induced asthma is still unknown. To determine whether toluene diisocyanate stimulates the 'efferent' function of peripheral endings of capsaicin-sensitive sensory nerves, we investigated the effect of toluene diisocyanate in the rat isolated urinary bladder, a preparation in which the action of capsaicin has been well characterized. Toluene diisocyanate (0.03-3 mM) produced a concentration-dependent contraction of the bladder strips. Its maximal effect was about 50% of the response to capsaicin (1 microM). Previous exposure of the strips to capsaicin followed by washing out produced complete unresponsiveness, both to the first exposure to toluene diisocyanate and to a second exposure of capsaicin. Further, the response to both toluene diisocyanate and capsaicin was completely prevented by extrinsic bladder denervation, achieved by bilateral removal of pelvic ganglia (72 h before). Repeated exposure of the rat bladder to toluene diisocyanate reduced the capsaicin-evoked release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), taken as biochemical marker of activation of these sensory nerves. These experiments provide the first evidence that toluene diisocyanate activates directly or indirectly the efferent function of capsaicin-sensitive primary sensory nerves.