Activation of the Integrated Stress Response in Nociceptors Drives Methylglyoxal-Induced Pain

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dc.contributor.ORCID0000-0002-3768-6996 (Campbell, ZT)
dc.contributor.ORCID0000-0002-6971-6221 (Price, TJ)
dc.contributor.authorBarragan-Iglesias, Paulino
dc.contributor.authorKuhn, Jasper
dc.contributor.authorVidal-Cantu, Guadalupe C.
dc.contributor.authorBelen Salinas-Abarca, Ana
dc.contributor.authorGranados-Soto, Vinicio
dc.contributor.authorDussor, Gregory
dc.contributor.authorCampbell, Zachary T.
dc.contributor.authorPrice, Theodore J.
dc.contributor.utdAuthorDussor, Gregory
dc.contributor.utdAuthorCampbell, Zachary T.
dc.contributor.utdAuthorPrice, Theodore J.
dc.date.accessioned2020-07-24T23:06:43Z
dc.date.available2020-07-24T23:06:43Z
dc.date.issued2019-01
dc.descriptionDue to copyright restrictions and/or publisher's policy full text access from Treasures at UT Dallas is limited to current UTD affiliates (use the provided Link to Article).
dc.description.abstractMethylglyoxal (MGO) is a reactive glycolytic metabolite associated with painful diabetic neuropathy at plasma concentrations between 500 nM and 5 μM. The mechanisms through which MGO causes neuropathic pain at these pathological concentrations are not known. Because MGO has been linked to diabetic neuropathic pain, which is prevalent and poorly treated, insight into this unsolved biomedical problem could lead to much needed therapeutics. Our experiments provide compelling evidence that ~ 1-μM concentrations of MGO activate the integrated stress response (ISR) in IB4-positive nociceptors in the dorsal root ganglion (DRG) of mice in vivo and in vitro. Blocking the integrated stress response with a specific inhibitor (ISRIB) strongly attenuates and reverses MGO-evoked pain. Moreover, ISRIB reduces neuropathic pain induced by diabetes in both mice and rats. Our work elucidates the mechanism of action of MGO in the production of pain at pathophysiologically relevant concentrations and suggests a new pharmacological avenue for the treatment of diabetic and other types of MGO-driven neuropathic pain.
dc.description.departmentSchool of Behavioral and Brain Sciences
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.description.departmentCenter for Advanced Pain Studies
dc.description.sponsorshipNIH Grants R01NS065926, R01NS102161, and R01NS100788; Conacyt grants CB-2012/179294 and CB-2013/222720
dc.identifier.bibliographicCitationBarragan-Iglesias, Paulino, Jasper Kuhn, Guadalupe C. Vidal-Cantu, Ana Belen Salinas-Abarca, et al. 2019. "Activation of the integrated stress response in nociceptors drives methylglyoxal-induced pain." Pain 160(1): 160-171, doi: 10.1097/j.pain.0000000000001387
dc.identifier.issn0304-3959
dc.identifier.issue1
dc.identifier.urihttp://dx.doi.org/10.1097/j.pain.0000000000001387
dc.identifier.urihttps://hdl.handle.net/10735.1/8737
dc.identifier.volume160
dc.language.isoen
dc.publisherLippincott Williams & Wilkins
dc.rights©2018 International Association for the Study of Pain
dc.source.journalPain
dc.subjectMethylglyoxal
dc.subjectIsolectin B4 neurons
dc.subjectEndoplasmic Reticulum Stress
dc.subjectProtein-synthesis
dc.subjectColocalization
dc.subjectPlasticity
dc.subjectAnesthesiology
dc.subject.meshIsrib
dc.subject.meshTRPA1 Cation Channels
dc.subject.meshPeripheral Nervous System
dc.titleActivation of the Integrated Stress Response in Nociceptors Drives Methylglyoxal-Induced Pain
dc.type.genrearticle

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Price, Theodore J.
Campbell, Zachary T.
Dussor, Gregory