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

Journal

Pain Lippincott, Williams & Wilkins

Book Volume: 160

Pages Range: 2497-2507

Journal Issue: 11

DOI: 10.1097/j.pain.0000000000001644

Abstract

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.

Authors with CRIS profile

Miriam Düll Institut für Physiologie und Pathophysiologie Marion Strupf Lehrstuhl für Physiologie Susanne Sauer Lehrstuhl für Physiologie Barbara Namer Medizinische Fakultät

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

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. https://doi.org/10.1097/j.pain.0000000000001644

MLA:

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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