• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    The Contribution of TRPV1 S801 Phosphorylation to Nociception and Inflammatory Pain in Vivo

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Joseph_umaryland_0373D_11207.pdf
    Embargo:
    2021-07-01
    Size:
    1.343Mb
    Format:
    PDF
    Download
    Author
    Joseph, John
    Advisor
    Chung, Man-Kyo
    Date
    2020
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Transient receptor potential vanilloid subtype 1 (TRPV1) is a nonselective cation permeable channel activated by painful stimuli, such as capsaicin and noxious heat, and enriched in many primary afferent neurons of the pain pathway. During inflammation, chemical mediators activate protein kinases (such as PKC) that phosphorylate TRPV1 and thereby enhance its function, which results in nociceptor sensitization. And this can result in a lower threshold for pain. However, the causal relationships between TRPV1 phosphorylation and pathological pain remain unexplored. To directly investigate the roles of one specific TRPV1 phosphorylation event in vivo, we genetically altered a major PKC phosphorylation site, mouse TRPV1 S801, to alanine. The TRPV1 expression pattern in sensory neurons of S801A knock-in (KI) mice was comparable to that in wildtype (WT) controls. In sensory neurons from KI mice, following the activation of PKC, the usual increase of capsaicin-induced currents was substantially impaired. Thermal hyperalgesia induced by PMA or burn injury in KI was identical to WT. Thermal hyperalgesia was only marginally attenuated in KI mice duirng inflammation. In contrast, PMA-evoked nocifensive responses and hyperalgesia to capsaicin were significantly attenuated in the hindpaws of KI mice. Ongoing pain from inflamed masseter muscle was also reduced in KI mice, and the pain was further inhibited by the TRPV1 antagonist AMG9810. These results suggest that PKC-mediated phosphorylation of TRPV1 S801 contributes to inflammation-mediated sensitization of TRPV1 to ligand, but not heat, in vivo. Further, this suggests that interference with TRPV1 S801 phosphorylation might represent a potential way to reduce inflammatory pain in the clinic, yet spare basal sensitivity and produce fewer side effects than with a more general TRPV1 inhibition.
    Description
    Neuroscience
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    TRPV1
    Inflammation
    Pain
    Phosphorylation
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14641
    Collections
    Theses and Dissertations School of Dentistry
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.