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dc.contributor.authorGuo, W.
dc.contributor.authorImai, S.
dc.contributor.authorYang, J.-L.
dc.date.accessioned2019-06-05T18:28:19Z
dc.date.available2019-06-05T18:28:19Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85057105789&doi=10.3389%2ffnint.2018.00049&partnerID=40&md5=fe079fc73a68395f6a46722f7235f3a6
dc.identifier.urihttp://hdl.handle.net/10713/9460
dc.description.abstractBone marrow stromal cells (BMSCs) produce long-lasting attenuation of pain hypersensitivity. This effect involves BMSC’s ability to interact with the immune system and activation of the endogenous opioid receptors in the pain modulatory circuitry. The nuclear factor kappa B (NF-κB) protein complex is a key transcription factor that regulates gene expression involved in immunity. We tested the hypothesis that the NF-κB signaling plays a role in BMSC-induced pain relief. We focused on the rostral ventromedial medulla (RVM), a key structure in the descending pain modulatory pathway, that has been shown to play an important role in BMSC-produced antihyperalgesia. In Sprague-Dawley rats with a ligation injury of the masseter muscle tendon (TL), BMSCs (1.5 M/rat) from donor rats were infused i.v. at 1 week post-TL. P65 exhibited predominant neuronal localization in the RVM with scattered distribution in glial cells. At 1 week, but not 8 weeks after BMSC infusion, western blot and immunostaining showed that p65 of NF-κB was significantly increased in the RVM. Given that chemokine signaling is critical to BMSCs’ pain-relieving effect, we further evaluated a role of chemokine signaling in p65 upregulation. Prior to infusion of BMSCs, we transduced BMSCs with Ccl4 shRNA, incubated BMSCs with RS 102895, a CCR2b antagonist, or maraviroc, a CCR5 antagonist. The antagonism of chemokines significantly reduced BMSC-induced upregulation of p65, suggesting that upregulation of p65 was related to BMSCs’ pain-relieving effect. We then tested the effect of a selective NF-κB activation inhibitor, BAY 11-7082. The mechanical hyperalgesia of the rat was assessed with the von Frey method. In the pre-treatment experiment, BAY 11-7082 (2.5 and 25 pmol) was injected into the RVM at 2 h prior to BMSC infusion. Pretreatment with BAY 11-7082 attenuated BMSCs’ antihyperalgesia, but post-treatment at 5 weeks post-BMSC was not effective. On the contrary, in TL rats receiving BAY 11-7082 without BMSCs, TL-induced hyperalgesia was attenuated, consistent with dual roles of NF-κB in pain hypersensitivity and BMSC-produced pain relief. These results indicate that the NF-κB signaling pathway in the descending circuitry is involved in initiation of BMSC-produced behavioral antihyperalgesia. Copyright 2018 Guo, Imai, Yang, Zou, Li, Xu, Moudgil, Dubner, Wei and Ren.en_US
dc.description.sponsorshipThis work was supported by the Maryland Stem Cell Foundation grant 2014-MSCRFI-0584 (KR); NIH grants: DE025137 (KR), NS019296 (FW), DE021804 (RD); The Team-Building Project for Stem Cell Research (K00008), SYSU (HL).en_US
dc.description.urihttps://dx.doi.org/10.3389/fnint.2018.00049en_US
dc.language.isoen-USen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Integrative Neuroscience
dc.subjectBAY 11-7082en_US
dc.subjectChemokineen_US
dc.subjectMesenchymal stromal cellsen_US
dc.subjectOrofacial painen_US
dc.subjectRostral ventromedial medullaen_US
dc.subjectTendon ligationen_US
dc.titleNF-KappaB pathway is involved in bone marrow stromal cell-produced pain reliefen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fnint.2018.00049


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