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    Sex differences in the expression of calcitonin gene-related peptide receptor components in the spinal trigeminal nucleus

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    Author
    Ji, Yadong
    Rizk, Alexandra
    Voulalas, Pamela
    Aljohani, Hanan
    Akerman, Simon
    Dussor, Gregory
    Keller, Asaf
    Masri, Radi
    Date
    2019-04-23
    Journal
    Neurobiology of Pain
    Publisher
    Elsevier B.V.
    Type
    Article
    
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    https://doi.org/10.1016/j.ynpai.2019.100031
    Abstract
    Background and purpose: Calcitonin gene-related peptide (CGRP)plays an important role in migraine pathophysiology. CGRP acts primarily by activating a receptor composed of 3 proteins: calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and receptor component protein (RCP). We tested the hypothesis that sex differences exist in protein levels of two key components of this CGRP receptor: CLR and RCP. Methods: We used specific antibodies to assess baseline protein levels of CLR and RCP in the spinal trigeminal nucleus caudalis (SpVc)and upper cervical spinal cord of both male and female rats. We also tested if manipulations that knock-down the expression of RCP in SpVc, using locally-mediated gene transfer of short hairpin RNA (shRNA), ameliorate pain in an animal model of intracranial migraine-like pain induced by chemical noxious stimulation of the meninges. To assess pain, we used tests of ongoing pain (rat face grimace test and freezing behavior)and tests of facial mechanical hypersensitivity and allodynia. Results: There was no difference in CLR levels between male and female animals (p > 0.11)in SpVc and the upper cervical cord. However, female animals exhibited greater baseline levels of RCP (up to 3-fold higher)compared to males (p < 0.002). The knock-down of RCP expression in SpVc attenuated mechanical facial allodynia induced by chemical noxious stimulation of the meninges, but had little effect on ongoing pain behaviors in female and male animals. Conclusions: RCP is an integral component of the CGRP receptor and may play a key role in mediating CGRP induced central sensitization after noxious stimulation of the meninges. RCP expression in the SpVc and upper cervical cord is sexually dimorphic, with higher levels of expression in females. This dimorphism may be related to the increased incidence of migraines in females–a hypothesis that should be tested in the future. © 2019 The Authors
    Rights/Terms
    Attribution 4.0 International (CC BY 4.0)
    Keyword
    Allodynia
    CGRP
    Headache
    Meninges
    Migraine
    Trigeminal
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064672369&origin=inward; http://hdl.handle.net/10713/9003
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ynpai.2019.100031Get
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    UMB Open Access Articles 2019

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