Papers of the Week

The endogenous metabolite methylglyoxal (MG) accumulates in diabetic patients with neuropathic pain. MG could be a mediator of diabetes-induced neuropathic pain via TRPA1 activation and sensitization of the voltage-gated sodium channel subtype 1.8. In this study, we tested the algogenic and sensitizing effect of MG in healthy human subjects using intracutaneous microinjections. The involvement of C-fibers was assessed via selective A-fiber nerve block, axon-reflex-erythema and via single nerve fiber recordings in humans (microneurography). Involvement of the transduction channels TRPA1 and TRPV1 in MG-induced pain sensation was investigated with specific ion channel blockers. We showed for the first time in healthy humans that MG induces pain, axon-reflex-erythema and long-lasting hyperalgesia via the activation of C-nociceptors. Predominantly the subclass of mechano-insensitive C-fibers is activated by MG. A-fibers contribute only negligibly to the burning pain sensation. Selective harmacological blockade of TRPA1 or TRPV1 showed that TRPA1 is crucially involved in MG-induced chemical pain sensation and heat hyperalgesia. In conclusion, the ctions of MG via TRPA1 activation on predominantly mechanoinsensitive C-fibers might be involved in spontaneously perceived pain in diabetic neuropathy and hyperalgesia as well as allodynia.