PMID- 29467623 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 12 DP - 2018 TI - eIF4E Phosphorylation Influences Bdnf mRNA Translation in Mouse Dorsal Root Ganglion Neurons. PG - 29 LID - 10.3389/fncel.2018.00029 [doi] LID - 29 AB - Plasticity in dorsal root ganglion (DRG) neurons that promotes pain requires activity-dependent mRNA translation. Protein synthesis inhibitors block the ability of many pain-promoting molecules to enhance excitability in DRG neurons and attenuate behavioral signs of pain plasticity. In line with this, we have recently shown that phosphorylation of the 5' cap-binding protein, eIF4E, plays a pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming. However, mRNA targets of eIF4E phosphorylation have not been elucidated in the DRG. Brain-derived neurotrophic factor (BDNF) signaling from nociceptors in the DRG to spinal dorsal horn neurons is an important mediator of hyperalgesic priming. Regulatory mechanisms that promote pain plasticity via controlling BDNF expression that is involved in promoting pain plasticity have not been identified. We show that phosphorylation of eIF4E is paramount for Bdnf mRNA translation in the DRG. Bdnf mRNA translation is reduced in mice lacking eIF4E phosphorylation (eIF4E(S209A) ) and pro-nociceptive factors fail to increase BDNF protein levels in the DRGs of these mice despite robust upregulation of Bdnf-201 mRNA levels. Importantly, bypassing the DRG by giving intrathecal injection of BDNF in eIF4E(S209A) mice creates a strong hyperalgesic priming response that is normally absent or reduced in these mice. We conclude that eIF4E phosphorylation-mediated translational control of BDNF expression is a key mechanism for nociceptor plasticity leading to hyperalgesic priming. FAU - Moy, Jamie K AU - Moy JK AD - School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States. AD - Department of Pharmacology, University of Arizona, Tucson, AZ, United States. FAU - Khoutorsky, Arkady AU - Khoutorsky A AD - Department of Anesthesia, McGill University, Montreal, QC, Canada. AD - Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada. FAU - Asiedu, Marina N AU - Asiedu MN AD - School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States. AD - Department of Pharmacology, University of Arizona, Tucson, AZ, United States. FAU - Dussor, Gregory AU - Dussor G AD - School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States. AD - Department of Pharmacology, University of Arizona, Tucson, AZ, United States. FAU - Price, Theodore J AU - Price TJ AD - School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States. AD - Department of Pharmacology, University of Arizona, Tucson, AZ, United States. LA - eng GR - R01 GM102575/GM/NIGMS NIH HHS/United States GR - R01 NS065926/NS/NINDS NIH HHS/United States GR - R01 NS098826/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20180206 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 PMC - PMC5808250 OTO - NOTNLM OT - BDNF OT - DRG OT - eIF4E phosphorylation OT - hyperalgesic priming OT - pain EDAT- 2018/02/23 06:00 MHDA- 2018/02/23 06:01 PMCR- 2018/01/01 CRDT- 2018/02/23 06:00 PHST- 2017/10/28 00:00 [received] PHST- 2018/01/23 00:00 [accepted] PHST- 2018/02/23 06:00 [entrez] PHST- 2018/02/23 06:00 [pubmed] PHST- 2018/02/23 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2018.00029 [doi] PST - epublish SO - Front Cell Neurosci. 2018 Feb 6;12:29. doi: 10.3389/fncel.2018.00029. eCollection 2018.