Browsing by Author "Black, Brian J."
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Item The MNK–eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain(Society for Neuroscience) Moy, Jamie K.; Khoutorsky, A.; Black, Brian J.; Kuhn, Jasper L.; Barragán-Iglesias, Paulino; Megat, Salim; Burton, Michael D.; Burgos-Vega, Carolina C.; Melemedjian, O. K.; Boitano, S.; Vagner, J.; Gkogkas, C. G.; Pancrazio, Joseph J.; Mogil, J. S.; Dussor, Gregory; Sonenberg, N.; Price, Theodore J.; 0000 0001 3721 4764 (Dussor, G); 0000-0001-8579-5540 (Moy, JK); 0000-0001-8571-6486 (Black, B); 0000-0001-6524-9411 (Kuhn JL); 0000-0003-3178-8606 (Barragán-Iglesias, P); 0000-0002-6971-6221 (Price, TJ); Moy, Jamie K.; Asiedu, Marina N.; Black, Brian J.; Kuhn, Jasper L.; Barragán-Iglesias, Paulino; Megat, Salim; Burton, Michael D.; Burgos-Vega, Carolina C.; Pancrazio, Joseph J.; Dussor, Gregory; Price, Theodore J.Injury-induced sensitization of nociceptors contributes to pain states and the development of chronic pain. Inhibiting activity-dependent mRNA translation through mechanistic target of rapamycin and mitogen-activated protein kinase (MAPK) pathways blocks the development of nociceptor sensitization. These pathways convergently signal to the eukaryotic translation initiation factor (eIF) 4F complex to regulate the sensitization of nociceptors, but the details of this process are ill defined. Here we investigated the hypothesis that phosphorylation of the 5β cap-binding protein eIF4E by its specific kinase MAPK interacting kinases (MNKs) 1/2 is a key factor in nociceptor sensitization and the development of chronic pain. Phosphorylation of ser209 on eIF4E regulates the translation of a subset of mRNAs. We show that pronociceptive and inflammatory factors, such as nerve growth factor (NGF), interleukin-6 (IL-6), and carrageenan, produce decreased mechanical and thermal hypersensitivity, decreased affective pain behaviors, and strongly reduced hyperalgesic priming in mice lacking eIF4E phosphorylation (eIF4ES209A). Tests were done in both sexes, and no sex differences were found. Moreover, in patch-clamp electrophysiology and Ca2+ imaging experiments on dorsal root ganglion neurons, NGF- and IL-6-induced increases in excitability were attenuated in neurons from eIF4ES209A mice. These effects were recapitulated in Mnk1/2-/- mice and with the MNK1/2 inhibitor cercosporamide. We also find that cold hypersensitivity induced by peripheral nerve injury is reduced in eIF4ES209A and Mnk1/2-/- mice and following cercosporamide treatment. Our findings demonstrate that the MNK1/2–eIF4E signaling axis is an important contributing factor to mechanisms of nociceptor plasticity and the development of chronic pain.Item The Effect of Microfluidic Geometry on Myoblast Migration(MDPI AG) Atmaramani, Rahul; Black, Brian J.; Lam, Kevin H.; Sheth, Vinit M.; Pancrazio, Joseph J.; Schmidtke, David W.; Alsmadi, Nesreen Zoghoul; 0000-0002-9325-547X (Atmaramani, R); 0000-0001-8276-3690 (Pancrazio, JJ); 0000-0001-6404-318X (Schmidtke, DW); Atmaramani, Rahul; Black, Brian J.; Lam, Kevin H.; Sheth, Vinit M.; Pancrazio, Joseph J.; Schmidtke, David W.; Alsmadi, Nesreen ZoghoulIn vitro systems comprised of wells interconnected by microchannels have emerged as a platform for the study of cell migration or multicellular models. In the present study, we systematically evaluated the effect of microchannel width on spontaneous myoblast migration across these microchannels-from the proximal to the distal chamber. Myoblast migration was examined in microfluidic devices with varying microchannel widths of 1.5-20 µm, and in chips with uniform microchannel widths over time spans that are relevant for myoblast-to-myofiber differentiation in vitro. We found that the likelihood of spontaneous myoblast migration was microchannel width dependent and that a width of 3 µm was necessary to limit spontaneous migration below 5% of cells in the seeded well after 48 h. These results inform the future design of Polydimethylsiloxane (PDMS) microchannel-based co-culture platforms as well as future in vitro studies of myoblast migration. © 2019 by the authors.