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

Düll M, Riegel K, Tappenbeck J, Ries V, Strupf M, Fleming T, Sauer S, Namer B (2019)

Publication Type: Journal article

Publication year: 2019


Book Volume: 160

Pages Range: 2497-2507

Journal Issue: 11

DOI: 10.1097/j.pain.0000000000001644


The endogenous metabolite methylglyoxal (MG) accumulates in diabetic patients with neuropathic pain. Methylglyoxal could be a mediator of diabetes-induced neuropathic pain through 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 through selective A-fiber nerve block, axon-reflex-erythema, and through 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 through 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 pharmacological blockade of TRPA1 or TRPV1 showed that TRPA1 is crucially involved in MG-induced chemical pain sensation and heat hyperalgesia. In conclusion, the actions of MG through TRPA1 activation on predominantly mechano-insensitive C fibers might be involved in spontaneously perceived pain in diabetic neuropathy and hyperalgesia as well as allodynia.

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Düll, M., Riegel, K., Tappenbeck, J., Ries, V., Strupf, M., Fleming, T.,... Namer, B. (2019). Methylglyoxal causes pain and hyperalgesia in human through C-fiber activation. Pain, 160(11), 2497-2507.


Düll, Miriam, et al. "Methylglyoxal causes pain and hyperalgesia in human through C-fiber activation." Pain 160.11 (2019): 2497-2507.

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