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

• Verfasst von: Düll, Miriam [VerfasserIn]
• Verfasst von: Riegel, Kathrin [VerfasserIn]
• Verfasst von: Tappenbeck, Julia [VerfasserIn]
• Verfasst von: Ries, Vivien [VerfasserIn]
• Verfasst von: Strupf, Marion [VerfasserIn]
• Verfasst von: Fleming, Thomas [VerfasserIn]
• Verfasst von: Sauer, Susanne K. [VerfasserIn]
• Verfasst von: Namer, Barbara [VerfasserIn]
• Titel: Methylglyoxal causes pain and hyperalgesia in human through C-fiber activation
• Verf.angabe: Miriam M. Düll, Kathrin Riegel, Julia Tappenbeck, Vivien Ries, Marion Strupf, Thomas Fleming, Susanne K. Sauer, Barbara Namer
• E-Jahr: 2019
• Jahr: 18 June 2019
• Fussnoten: Gesehen am 03.04.2020
• Titel Quelle: Enthalten in: Pain
• Ort Quelle: New York, NY [u.a.] : Lippincott Williams and Wilkins, 1975
• Jahr Quelle: 2019
• Band/Heft Quelle: 160(2019), 11, Seite 2497-2507
• ISSN Quelle: 1872-6623
• DOI: doi:10.1097/j.pain.0000000000001644
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1694038254

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.