Sex Differences in the Expression of Calcitonin Gene-Related Peptide Receptor Components in the Spinal Trigeminal Nucleus

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dc.contributor.authorJi, Y.
dc.contributor.authorRizk, A.
dc.contributor.authorVoulalas, P.
dc.contributor.authorAljohani, H.
dc.contributor.authorAkerman, S.
dc.contributor.authorDussor, Gregory
dc.contributor.authorKeller, A.
dc.contributor.authorMasri, R.
dc.contributor.utdAuthorDussor, Gregory
dc.date.accessioned2020-02-17T21:02:15Z
dc.date.available2020-02-17T21:02:15Z
dc.date.issued2019-04-24
dc.description.abstractBackground 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
dc.description.departmentSchool of Behavioral and Brain Sciences
dc.description.sponsorshipNational Institute of Neurological Disorders and Stroke of the National Institutes of Health grants R01NS099245 and R01NS104200
dc.identifier.bibliographicCitationJi, Y., A. Rizk, P. Voulalas, H. Aljohani, et al. 2019. "Sex differences in the expression of calcitonin gene-related peptide receptor components in the spinal trigeminal nucleus." Neurobiology of Pain 6: art. 100031, doi: 10.1016/j.ynpai.2019.100031
dc.identifier.issn2452-073X
dc.identifier.urihttp://dx.doi.org/10.1016/j.ynpai.2019.100031
dc.identifier.urihttps://hdl.handle.net/10735.1/7269
dc.identifier.volume6
dc.language.isoen
dc.publisherElsevier B.V.
dc.rightsCC BY 4.0 (Attribution)
dc.rights©2019 The Authors
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.source.journalNeurobiology of Pain
dc.subjectAllodynia
dc.subjectCalcitonin gene-related peptide
dc.subjectHeadache
dc.subjectMeninges
dc.subjectMigraine
dc.subjectTrigeminal nerve
dc.titleSex Differences in the Expression of Calcitonin Gene-Related Peptide Receptor Components in the Spinal Trigeminal Nucleus
dc.type.genrearticle

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