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Mutations in the\n                    <jats:italic>FMR1<\/jats:italic>\n                    gene that hinder or ablate FMRP function cause Fragile X Syndrome (FXS), a disorder associated with sensory processing dysfunction. FXS premutations are associated with increased FMRP expression and neurological impairments including sex dimorphic presentations of chronic pain. In mice, FMRP ablation causes dysregulated dorsal root ganglion (DRG) neuron excitability and synaptic vesicle exocytosis, spinal circuit activity, and decreased translation\u2010dependent nociceptive sensitization. Activity\u2010dependent, local translation is a key mechanism for enhancing primary nociceptor excitability that promotes pain in animals and humans. These works indicate that FMRP likely regulates nociception and pain at the level of the primary nociceptor or spinal cord. Therefore, we sought to better understand FMRP expression in the human DRG and spinal cord using immunostaining in organ donor tissues. We find that FMRP is highly expressed in DRG and spinal neuron subsets with substantia gelatinosa exhibiting the most abundant immunoreactivity in spinal synaptic fields. Here, it is expressed in nociceptor axons. FMRP puncta colocalized with Nav1.7 and TRPV1 receptor signals suggesting a pool of axoplasmic FMRP localizes to plasma membrane\u2010associated loci in these branches. Interestingly, FMRP puncta exhibited notable colocalization with calcitonin gene\u2010related peptide (CGRP) immunoreactivity selectively in female spinal cord. Our results support a regulatory role for FMRP in human nociceptor axons of the dorsal horn and implicate it in the sex dimorphic actions of CGRP signaling in nociceptive sensitization and chronic pain.\n                  <\/jats:p>","DOI":"10.1002\/cne.25463","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T01:52:32Z","timestamp":1676944352000},"page":"814-835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Characterization of Fragile X Mental Retardation Protein expression in human nociceptors and their axonal projections to the spinal dorsal horn"],"prefix":"10.1002","volume":"531","author":[{"given":"Molly E.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Center for Advanced Pain Studies, School of Behavioral and Brain Sciences University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Cook","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Studies, School of Behavioral and Brain Sciences University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9646-1850","authenticated-orcid":false,"given":"Stephanie","family":"Shiers","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Studies, School of Behavioral and Brain Sciences University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Tavares\u2010Ferreira","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Studies, School of Behavioral and Brain Sciences University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1066-253X","authenticated-orcid":false,"given":"Armen N.","family":"Akopian","sequence":"additional","affiliation":[{"name":"Department of Endodontics UT Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Dussor","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Studies, School of Behavioral and Brain Sciences University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-6221","authenticated-orcid":false,"given":"Theodore J.","family":"Price","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Studies, School of Behavioral and Brain Sciences University of Texas at Dallas  Richardson Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2020.108997"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw381"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23123"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003378"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3344\/kjp.2016.29.2.103"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0099\u201004.2004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896\u20106273(03)00090\u20104"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11737"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6286\u201010.2011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12109"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00449.2010"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0364\u201019.2019"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26070"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.02.041"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200601087"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896\u20106273(03)00718\u20109"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409314111"},{"key":"e_1_2_9_19_1","unstructured":"Bauchwitz D. 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