Aims: Diabetic neuropathy associated with pain occurs in about on third of diabetic patients. There is evidence that exaggerated glycoliytic metabolism increases the excitability of primary sensory neurons and therefore may contribute to the development of painful sensations. In this condition, the highly reactive and cytotoxic metabolite methylglyoxal (MG, aldehyde form of pyruvic acid) accumulates in plasma of diabetics (> 600nm). We studied a possible involvement of TRP channels in MG-mediated excitation and sensitization of nociceptors. Methods: MG effects were investigated using the isolated mouse skin/nerve preparation to record from C-nociceptors. Activation of cultured mouse dorsal root ganglion (DRG) neurons and transfected HEK cells was studied using calcium imaging and patch-clamp recordings, respectively. Results: At 1 and 10mM concentrations MG caused activation of C-fibers recorded from skin/nerve preparations. In DRG neurons of mice application of MG at concentrations of 1 and 3 mM induced a prolonged increase in intracellular calcium within 90s by about 50 and 60 %, respectively; these calcium influxes were absent in TRPA 1-/- DRGs. Using the patch-clamp technique, TRPA1-transfected HEK cells exhibited inward currents in response to 1mM MG and more. Concentrations of 3 and 10 mM MG activated all cells recorded, while no activation was found in TRPV1-tranfected HEK cells. Conclusion: These results demonstrate that MG acutely activates primary nociceptive neurons at higher concentrations by activation of TRPA1 channels; longterm effects of lower, clinically relevant concentrations are under investigation