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"A recent study also reported that chemokine ligand 2 can induce NF-κB activation via PKC and lead to Nav1.8 upregulation in DRG neurons."
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"However, the involvement of other transcription factors or molecules in ET-1/ET receptor-mediated Nav1.8 upregulation in HbSS DRG could not be excluded.In conclusion, this study provides evidence for one possible mechanism by which ET-1/ET receptors contribute to SCD-associated pain likely through the NF-κB-triggered upregulation of Nav1.8 in primary sensory neurons."
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"In addition, single-cell PCR further showed that 4 out of 5 neurons expressed CXCR5, and all of them expressed Nav1.8 (Fig. 4D), further supporting the colocalization of CXCR5 with Nav1.8 in DRG neurons.We then checked the role of Nav1.8 on CFA- or CXCL13-induced hyperexcitablity of DRG neurons using A-803467, a potent and selective Nav1.8 sodium channel blocker28."
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"Nav1.8 channels produce the majority of the inward current during the action potential (AP) upstroke in the dorsal root ganglion (DRG) neurons in which they exist [9], most of which are nociceptors [10]."
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"The levels of Scn10a mRNA (encoding Nav1.8) and Scn11a mRNA (encoding Nav1.9, another TTX-R sodium channel) were elevated in HbSS DRG (Figure 6A)."
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"Thus, it is of interest to further examine whether the expression of other ion channels including delayed rectifier potassium channels differs between HbAA and HbSS DRG neurons and whether these differences are ET receptor-dependent.NF-κB may be a key modulator of ET receptor-dependent Nav1.8 upregulation in HbSS DRG."
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"These data suggest that NP application produces pain-related behavior and potentiates sodium current density of DRG neurons, which is most likely mediated by enhanced expression of NaV1.7 and NaV1.8."
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"Taken together, our findings suggest the participation of NF-κB in ET receptor-dependent Nav1.8 upregulation in HbSS DRG neurons (Online Supplementary Figure S11)."
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"The results indicated that CCD induced multiple pain-related behaviors and the expression of CXCR4, Nav1.8 and Nav1.9 was significantly increased in compressed dorsal root ganglion (DRG) neurons."
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"The transcription factor, NF-κB, may be upstream of Nav1.8 upregulation in DRG neurons and is activated by ET-1."
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"Using ChIP analyses, a fragment within the Scn10a promoter was amplified from a complex immunoprecipitated with an anti-p65 antibody (Figure 8E), indicating the binding of p65 to the Scn10a gene promoter in the DRG."
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"Although previous studies demonstrated that the increased expression of Nav1.8 might underlie the enhanced excitability of the DRG neurons, we did not have enough evidence to make the connection in the present study."
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