PMID- 31253755 OWN - NLM STAT- MEDLINE DCOM- 20200623 LR - 20220113 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 39 IP - 35 DP - 2019 Aug 28 TI - Differences between Dorsal Root and Trigeminal Ganglion Nociceptors in Mice Revealed by Translational Profiling. PG - 6829-6847 LID - 10.1523/JNEUROSCI.2663-18.2019 [doi] AB - Nociceptors located in the trigeminal ganglion (TG) and DRG are the primary sensors of damaging or potentially damaging stimuli for the head and body, respectively, and are key drivers of chronic pain states. While nociceptors in these two tissues show a high degree of functional similarity, there are important differences in their development lineages, their functional connections to the CNS, and recent genome-wide analyses of gene expression suggest that they possess some unique genomic signatures. Here, we used translating ribosome affinity purification to comprehensively characterize and compare mRNA translation in Scn10a-positive nociceptors in the TG and DRG of male and female mice. This unbiased method independently confirms several findings of differences between TG and DRG nociceptors described in the literature but also suggests preferential utilization of key signaling pathways. Most prominently, we provide evidence that translational efficiency in mechanistic target of rapamycin (mTOR)-related genes is higher in the TG compared with DRG, whereas several genes associated with the negative regulator of mTOR, AMP-activated protein kinase, have higher translational efficiency in DRG nociceptors. Using capsaicin as a sensitizing stimulus, we show that behavioral responses are greater in the TG region and this effect is completely reversible with mTOR inhibition. These findings have implications for the relative capacity of these nociceptors to be sensitized upon injury. Together, our data provide a comprehensive, comparative view of transcriptome and translatome activity in TG and DRG nociceptors that enhances our understanding of nociceptor biology.SIGNIFICANCE STATEMENT The DRG and trigeminal ganglion (TG) provide sensory information from the body and head, respectively. Nociceptors in these tissues are critical first neurons in the pain pathway. Injury to peripheral neurons in these tissues can cause chronic pain. Interestingly, clinical and preclinical findings support the conclusion that injury to TG neurons is more likely to cause chronic pain and chronic pain in the TG area is more intense and more difficult to treat. We used translating ribosome affinity purification technology to gain new insight into potential differences in the translatomes of DRG and TG neurons. Our findings demonstrate previously unrecognized differences between TG and DRG nociceptors that provide new insight into how injury may differentially drive plasticity states in nociceptors in these two tissues. CI - Copyright (c) 2019 the authors. FAU - Megat, Salim AU - Megat S AUID- ORCID: 0000-0003-2186-6770 AD - School of Behavioral and Brain Sciences. AD - Center for Advanced Pain Studies, and. FAU - Ray, Pradipta R AU - Ray PR AD - School of Behavioral and Brain Sciences. AD - Center for Advanced Pain Studies, and. FAU - Tavares-Ferreira, Diana AU - Tavares-Ferreira D AD - School of Behavioral and Brain Sciences. FAU - Moy, Jamie K AU - Moy JK AD - School of Behavioral and Brain Sciences. FAU - Sankaranarayanan, Ishwarya AU - Sankaranarayanan I AUID- ORCID: 0000-0002-6765-0281 AD - School of Behavioral and Brain Sciences. AD - Center for Advanced Pain Studies, and. FAU - Wanghzou, Andi AU - Wanghzou A AD - School of Behavioral and Brain Sciences. AD - Center for Advanced Pain Studies, and. FAU - Fang Lou, Tzu AU - Fang Lou T AD - Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, 75080. FAU - Barragan-Iglesias, Paulino AU - Barragan-Iglesias P AUID- ORCID: 0000-0003-3178-8606 AD - School of Behavioral and Brain Sciences. AD - Center for Advanced Pain Studies, and. FAU - Campbell, Zachary T AU - Campbell ZT AUID- ORCID: 0000-0002-3768-6996 AD - Center for Advanced Pain Studies, and. AD - Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, 75080. FAU - Dussor, Gregory AU - Dussor G AUID- ORCID: 0000-0002-1193-9238 AD - School of Behavioral and Brain Sciences. AD - Center for Advanced Pain Studies, and. FAU - Price, Theodore J AU - Price TJ AUID- ORCID: 0000-0002-6971-6221 AD - School of Behavioral and Brain Sciences, Theodore.price@utdallas.edu. AD - Center for Advanced Pain Studies, and. LA - eng GR - R01 NS065926/NS/NINDS NIH HHS/United States GR - R01 NS100788/NS/NINDS NIH HHS/United States GR - R01 NS102161/NS/NINDS NIH HHS/United States GR - R01 NS098826/NS/NINDS NIH HHS/United States GR - T32 NS073548/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190628 PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 SB - IM EIN - J Neurosci. 2022 Jan 26;42(4):717. PMID: 35022220 MH - Animals MH - Female MH - Ganglia, Spinal/*metabolism MH - Gene Expression Profiling MH - Male MH - Mice MH - Neurons/metabolism MH - Nociceptors/*metabolism MH - Signal Transduction MH - *Transcriptome MH - Trigeminal Ganglion/*metabolism PMC - PMC6733558 OTO - NOTNLM OT - DRG OT - TG OT - TRAP OT - mTOR OT - neuropathic pain EDAT- 2019/06/30 06:00 MHDA- 2020/06/24 06:00 PMCR- 2020/02/28 CRDT- 2019/06/30 06:00 PHST- 2018/10/15 00:00 [received] PHST- 2019/06/19 00:00 [revised] PHST- 2019/06/20 00:00 [accepted] PHST- 2019/06/30 06:00 [pubmed] PHST- 2020/06/24 06:00 [medline] PHST- 2019/06/30 06:00 [entrez] PHST- 2020/02/28 00:00 [pmc-release] AID - JNEUROSCI.2663-18.2019 [pii] AID - 2663-18 [pii] AID - 10.1523/JNEUROSCI.2663-18.2019 [doi] PST - ppublish SO - J Neurosci. 2019 Aug 28;39(35):6829-6847. doi: 10.1523/JNEUROSCI.2663-18.2019. Epub 2019 Jun 28.