| |  Online-Ressource |
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| Verfasst von: | Griggs, Ryan [VerfasserIn]  |
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| | Santos, Diogo F. [VerfasserIn] |
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| | Laird, Don E. [VerfasserIn] |
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| | Doolen, Suzanne [VerfasserIn] |
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| | Donahue, Renee R. [VerfasserIn] |
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| | Wessel, Caitlin R. [VerfasserIn] |
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| | Fu, Weisi [VerfasserIn] |
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| | Sinha, Ghanshyam P. [VerfasserIn] |
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| | Wang, Pingyuan [VerfasserIn] |
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| | Zhou, Jia [VerfasserIn] |
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| | Brings, Sebastian [VerfasserIn] |
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| | Fleming, Thomas [VerfasserIn] |
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| | Nawroth, Peter Paul [VerfasserIn] |
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| | Susuki, Keiichiro [VerfasserIn] |
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| | Taylor, Bradley K. [VerfasserIn] |
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| Titel: | Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes |
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| Verf.angabe: | Ryan B. Griggs, Diogo F. Santos, Don E. Laird, Suzanne Doolen, Renee R. Donahue, Caitlin R. Wessel, Weisi Fu, Ghanshyam P. Sinha, Pingyuan Wang, Jia Zhou, Sebastian Brings, Thomas Fleming, Peter P. Nawroth, Keiichiro Susuki, Bradley K. Taylor |
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| E-Jahr: | 2019 |
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| Jahr: | 23 February 2019 |
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| Umfang: | 11 S. |
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| Fussnoten: | Gesehen am 21.08.2019 |
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| Titel Quelle: | Enthalten in: Neurobiology of disease |
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| Ort Quelle: | Orlando, Fla. : Academic Press, 1994 |
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| Jahr Quelle: | 2019 |
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| Band/Heft Quelle: | 127(2019), Seite 76-86 |
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| ISSN Quelle: | 1095-953X |
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| Abstract: | Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related spinal mechanisms of PDN in type 2 diabetes using db/db mice, an established model of type 2 diabetes, and intrathecal injection of MG in conventional C57BL/6J mice. Administration of either a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the catabolic enzyme for MG, attenuated heat hypersensitivity in db/db mice. In C57BL/6J mice, intrathecal administration of MG produced signs of both evoked (heat and mechanical hypersensitivity) and affective (conditioned place avoidance) pain. MG-induced Ca2+ mobilization in lamina II dorsal horn neurons of C57BL/6J mice was exacerbated in db/db, suggestive of MG-evoked central sensitization. Pharmacological and/or genetic inhibition of transient receptor potential ankyrin subtype 1 (TRPA1), adenylyl cyclase type 1 (AC1), protein kinase A (PKA), or exchange protein directly activated by cyclic adenosine monophosphate (Epac) blocked MG-evoked hypersensitivity in C57BL/6J mice. Similarly, intrathecal administration of GERP10, or inhibitors of TRPA1 (HC030031), AC1 (NB001), or Epac (HJC-0197) attenuated hypersensitivity in db/db mice. We conclude that MG and sensitization of a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice. Our results warrant clinical investigation of MG scavengers, glyoxalase inducers, and spinally-directed pharmacological inhibitors of a MG-TRPA1-AC1-Epac pathway for the treatment of PDN in type 2 diabetes. |
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| DOI: | doi:10.1016/j.nbd.2019.02.019 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: http://dx.doi.org/10.1016/j.nbd.2019.02.019 |
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| | Volltext: http://www.sciencedirect.com/science/article/pii/S096999611930049X |
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| | DOI: https://doi.org/10.1016/j.nbd.2019.02.019 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | AC1 |
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| | Epac |
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| | Glyoxalase |
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| | Methylglyoxal |
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| | Neuropathic pain |
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| | Painful diabetic neuropathy |
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| | PKA |
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| | Spinal |
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| | TRPA1 |
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| | Type 2 diabetes |
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| K10plus-PPN: | 1671738438 |
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| Verknüpfungen: | → Zeitschrift |
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Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes / Griggs, Ryan [VerfasserIn]; 23 February 2019 (Online-Ressource)
