Correlation Engine 2.0
Clear Search sequence regions


  • adult (1)
  • allodynia (1)
  • c fiber (4)
  • calcium channels (2)
  • erythema (2)
  • female (1)
  • fiber (4)
  • heat (1)
  • human (5)
  • hyperalgesia (5)
  • ion channel (1)
  • neuralgia (1)
  • nociceptors (2)
  • patients (1)
  • sodium channel (1)
  • TRPA1 (5)
  • TRPV1 (2)
  • young adult (1)
  • Sizes of these terms reflect their relevance to your search.

    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.

    Citation

    Miriam M Düll, Kathrin Riegel, Julia Tappenbeck, Vivien Ries, Marion Strupf, Thomas Fleming, Susanne K Sauer, Barbara Namer. Methylglyoxal causes pain and hyperalgesia in human through C-fiber activation. Pain. 2019 Nov;160(11):2497-2507

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 31219946

    View Full Text