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

Düll, Miriam M.1; Riegel, Kathrin1; Tappenbeck, Julia1; Ries, Vivienne1; Strupf, Marion1; Fleming, Thomas2,3; Sauer, Susanne K.1; Namer, Barbara1,4

doi: 10.1097/j.pain.0000000000001644
Research Paper: PDF Only

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.

1Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany

2Department of Medicine I and Clinical Chemistry and Pharmacology, University of Heidelberg, INF 410, 69120 Heidelberg, Germany

3German Center for Diabetes Research (DZD), Germany

4Research group Neuroscience, Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, 52074 Aachen, Germany

Correspondence: Barbara Namer Institute of Physiology and Pathophysiology Universitätsstr. 17 91054 Erlangen Tel. +49 9131 85 22796

© 2019 International Association for the Study of Pain
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