Methylglyoxal causes pain and hyperalgesia in human through C-fiber activation
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 algogen...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
18 June 2019
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| In: |
Pain
Year: 2019, Volume: 160, Issue: 11, Pages: 2497-2507 |
| ISSN: | 1872-6623 |
| DOI: | 10.1097/j.pain.0000000000001644 |
| Online Access: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1097/j.pain.0000000000001644 Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/pain/fulltext/2019/11000/Methylglyoxal_causes_pain_and_hyperalgesia_in.10.aspx 
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| Author Notes: | Miriam M. Düll, Kathrin Riegel, Julia Tappenbeck, Vivien Ries, Marion Strupf, Thomas Fleming, Susanne K. Sauer, Barbara Namer |
| Summary: | 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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| Item Description: | Gesehen am 03.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1872-6623 |
| DOI: | 10.1097/j.pain.0000000000001644 |