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Papers of the Week

Papers: 15 Jun 2019 - 21 Jun 2019

Human Studies

2019 Nov




Methylglyoxal causes pain and hyperalgesia in human through C-fiber activation.


Düll MM, Riegel K, Tappenbeck J, Ries V, Strupf M, Fleming T, Sauer SK, Namer B
Pain. 2019 Nov; 160(11):2497-2507.
PMID: 31219946.


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.