Elucidating the Role of MOR-1K in Opioid-induced Hyperalgesia

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  • March 19, 2019
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  • Oladosu, Folabomi
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • Opioids commonly used in the treatment of acute and chronic pain have been reported to produce a paradoxical opioid-induced hyperalgesia (OIH) in a subset of the population. Recent evidence indicates a potential role for MOR-1K, an alternative splice variant of MOR-1, in OIH. Unlike its parent receptor, MOR-1K has a genetic association with increased pain sensitivity and facilitates cellular excitation upon opioid activation. Because of these properties, we hypothesize that MOR-1K contributes to OIH in genetically susceptible individuals. First, using a murine model of OIH alongside RNA interference-mediated knockdown and virally-mediated overexpression, we established MOR-1K plays a role in OIH development in a strain-specific manner, such that the 129S6 strain demonstrated an exclusively analgesic pain profile with decreased MOR-1K transcript levels, while the CXB7/ByJ strain demonstrated an exclusively hyperalgesic pain profile with increased MOR-1K transcript levels. These strain-specific divergences prompted subsequent genetic and molecular biologic studies, revealing a functional single nucleotide polymorphism in the MOR-1K gene locus that is associated with OIH and MOR-1K expression. Additionally, we have characterized MOR-1K cellular expression, demonstrating that the splice variant is expression in satellite glial cells in the dorsal root ganglion. Together, our findings suggest that MOR-1K is an essential contributor to OIH development. With further research, MOR-1K could be exploited as a target for development of antagonists that reduce or prevent OIH.
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  • In Copyright
Advisor
  • Maixner, William
  • Dykstra, Linda A.
  • Zylka, Mark J.
  • Ji, Ru-Rong
  • Nackley, Andrea
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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