Spinal Inhibition of P2XR or p38 Signaling Disrupts Hyperalgesic Priming in Male, but not Female, Mice

dc.contributor.ISNI0000 0001 3721 4764 (Dussor, G)
dc.contributor.ORCID0000-0002-6971-6221 (Price, TJ)
dc.contributor.authorPaige, Candler
dc.contributor.authorMaruthy, Gayathri B.
dc.contributor.authorMejia, Galo
dc.contributor.authorDussor, Gregory
dc.contributor.authorPrice, Theodore J.
dc.contributor.utdAuthorPaige, Candler
dc.contributor.utdAuthorMaruthy, Gayathri B.
dc.contributor.utdAuthorMejia, Galo
dc.contributor.utdAuthorDussor, Gregory
dc.contributor.utdAuthorPrice, Theodore J.
dc.date.accessioned2019-09-27T15:22:41Z
dc.date.available2019-09-27T15:22:41Z
dc.date.created2018-06-18
dc.descriptionFull text access from Treasures at UT Dallas is restricted to current UTD affiliates (use the provided Link to Article).
dc.description.abstractRecent studies have demonstrated sexual dimorphisms in the mechanisms contributing to the development of chronic pain. Here we tested the hypothesis that microglia might preferentially regulate hyperalgesic priming in male mice. We based this hypothesis on evidence that microglia preferentially contribute to neuropathic pain in male mice via ionotropic purinergic receptor (P2XR) or p38 mitogen-activated protein kinase (p38) signaling. Mice given a single-priming injection of the soluble human interleukin-6 receptor (IL-6r) and then a second injection of prostaglandin E2 (PGE2), which unmasks hyperalgesic priming, shows a significant increase in levels of activated microglia at 3 h following the PGE2 injection in both male and female mice. There was no change in microglia following PGE2. Intrathecal injection of the P2X3/4 inhibitor TNP-ATP blocked the initial response to IL-6r in both males and females, but only blocked hyperalgesic priming in male mice. Intrathecally applied p38 inhibitor, skepinone, had no effect on the initial response to IL-6r but attenuated hyperalgesic priming in males only. Neither TNP-ATP nor skepinone could reverse priming once it had already been established in male mice suggesting that these pathways must be inhibited early in the development of hyperalgesic priming to have an effect. Our work is consistent with previous findings that P2XR and p38 inhibition can lead to male-specific effects on pain behaviors in mice. However, given that we did not observe microglial activation at time points where these drugs were effective, our work also questions whether these effects can be completely attributed to microglia. © 2018 IBRO
dc.description.sponsorshipThis work was supported by NIH grants R01NS065926 and R01NS098826.
dc.identifier.bibliographicCitationPaige, C., G. B. Maruthy, G. Mejia, G. Dussor, et al. 2018. "Spinal Inhibition of P2XR or p38 Signaling Disrupts Hyperalgesic Priming in Male, but not Female, Mice." Neuroscience 385: 133-142, doi: 10.1016/j.neuroscience.2018.06.012
dc.identifier.issn0306-4522
dc.identifier.urihttps://hdl.handle.net/10735.1/6899
dc.identifier.volume385
dc.language.isoen
dc.publisherElsevier Ltd
dc.relation.urihttp://dx.doi.org/10.1016/j.neuroscience.2018.06.012
dc.rights©2018 IBRO
dc.source.journalNeuroscience
dc.subjectChronic pain
dc.subjectPurines—Receptors
dc.subjectMicroglia
dc.subjectp38 Mitogen-Activated Protein Kinases (p38)
dc.subjectSex differences
dc.subjectBrain-Derived Neurotrophic Factor
dc.subjectInterleukin 6
dc.subjectProstaglandin E2
dc.subjectReceptors, Purinergic P2X
dc.subjectPurinergic P2X Receptor Antagonists
dc.subjectReceptors, Purinergic P2X3
dc.subjectReceptors, Purinergic P2X4
dc.subjectFemale
dc.subjectHyperalgesia
dc.subjectMale
dc.subjectMice
dc.subjectNeuralgia
dc.subjectNociception
dc.subjectCellular signal transduction
dc.titleSpinal Inhibition of P2XR or p38 Signaling Disrupts Hyperalgesic Priming in Male, but not Female, Mice
dc.title.alternativeNeuroscience
dc.type.genrearticle

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