{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T10:35:55Z","timestamp":1793788555039,"version":"4.6.1"},"reference-count":86,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"632","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,2,16]]},"abstract":"<jats:p>\n                    Nociceptors are specialized sensory neurons that detect damaging or potentially damaging stimuli and are found in the dorsal root ganglia (DRG) and trigeminal ganglia. These neurons are critical for the generation of neuronal signals that ultimately create the perception of pain. Nociceptors are also primary targets for treating acute and chronic pain. Single-cell transcriptomics on mouse nociceptors has transformed our understanding of pain mechanisms. We sought to generate equivalent information for human nociceptors with the goal of identifying transcriptomic signatures of nociceptors, identifying species differences and potential drug targets. We used spatial transcriptomics to molecularly characterize transcriptomes of single DRG neurons from eight organ donors. We identified 12 clusters of human sensory neurons, 5 of which are C nociceptors, as well as 1 C low-threshold mechanoreceptors (LTMRs), 1 A\u03b2 nociceptor, 2 A\u03b4, 2 A\u03b2, and 1 proprioceptor subtypes. By focusing on expression profiles for ion channels, G protein\u2013coupled receptors (GPCRs), and other pharmacological targets, we provided a rich map of potential drug targets in the human DRG with direct comparison to mouse sensory neuron transcriptomes. We also compared human DRG neuronal subtypes to nonhuman primates showing conserved patterns of gene expression among many cell types but divergence among specific nociceptor subsets. Last, we identified sex differences in human DRG subpopulation transcriptomes, including a marked increase in calcitonin-related polypeptide alpha (\n                    <jats:italic>CALCA<\/jats:italic>\n                    ) expression in female pruritogen receptor\u2013enriched nociceptors. This comprehensive spatial characterization of human nociceptors might open the door to development of better treatments for acute and chronic pain disorders.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abj8186","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T13:52:46Z","timestamp":1645019566000},"source":"Crossref","is-referenced-by-count":502,"title":["Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0986-3630","authenticated-orcid":true,"given":"Diana","family":"Tavares-Ferreira","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9646-1850","authenticated-orcid":true,"given":"Stephanie","family":"Shiers","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-4201","authenticated-orcid":true,"given":"Pradipta R.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5667-1223","authenticated-orcid":true,"given":"Andi","family":"Wangzhou","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivekanand","family":"Jeevakumar","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishwarya","family":"Sankaranarayanan","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9295-6648","authenticated-orcid":true,"given":"Anna M.","family":"Cervantes","sequence":"additional","affiliation":[{"name":"Southwest Transplant Alliance , Dallas, TX 75231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4783-7591","authenticated-orcid":true,"given":"Jeffrey C.","family":"Reese","sequence":"additional","affiliation":[{"name":"Southwest Transplant Alliance , Dallas, TX 75231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7775-2062","authenticated-orcid":true,"given":"Alexander","family":"Chamessian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology , Washington University Pain Center, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan A.","family":"Copits","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology , Washington University Pain Center, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2177-2734","authenticated-orcid":true,"given":"Patrick M.","family":"Dougherty","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine, Division of Anesthesiology and Critical Care, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5428-4251","authenticated-orcid":true,"suffix":"IV","given":"Robert W.","family":"Gereau","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology , Washington University Pain Center, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-824X","authenticated-orcid":true,"given":"Michael D.","family":"Burton","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Dussor","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-6221","authenticated-orcid":true,"given":"Theodore J.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson TX 75080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn942"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0003-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2019.0286"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.04.005"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001217"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001866"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab048"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001973"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2021.03.017"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.016"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42843"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abe1648"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz063"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3881"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.039"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.021"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1900-1"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.07.026"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49679"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0150-2"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00271"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-100520-082639"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21725-z"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00806-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23831"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf2403"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/gen.40.02.16"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00787-0"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_3_31_2","unstructured":"D. W. Raible J. M. Ungos in Neural Crest Induction and Differentiation (Springer 2006) pp. 170\u2013180."},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.07.051"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254229"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-64831-6"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006884"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1979.sp012619"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.165613"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.229"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04049-3"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1983.49.1.111"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/379257a0"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.07.015"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.80.3.1082"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw1297"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature719"},{"key":"e_1_3_3_46_2","doi-asserted-by":"crossref","unstructured":"R. Przew\u0140ocki in Hormones Brain and Behavior (Elsevier 2002) pp. 691\u2013733.","DOI":"10.1016\/B978-012532104-4\/50014-7"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300820110"},{"key":"e_1_3_3_48_2","doi-asserted-by":"crossref","unstructured":"R. Nassini S. Materazzi S. Benemei P. Geppetti in Reviews of Physiology Biochemistry and Pharmacology vol. 167 (Springer 2014) pp. 1\u201343.","DOI":"10.1007\/112_2014_18"},{"key":"e_1_3_3_49_2","first-page":"2771","article-title":"Convergence of peptidergic and non-peptidergic protein markers in the human dorsal root ganglion and spinal dorsal horn","volume":"529","author":"Shiers S. I.","year":"2021","unstructured":"S. I. Shiers, I. Sankaranarayanan, V. Jeevakumar, A. Cervantes, J. C. Reese, T. J. Price, Convergence of peptidergic and non-peptidergic protein markers in the human dorsal root ganglion and spinal dorsal horn. J. Comp. Neurol. 529, 2771\u20132788 (2021).","journal-title":"J. Comp. Neurol."},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.066"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb02579.x"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20367"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00565.2003"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90482.2008"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01139.2002"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233765"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI122481"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237101"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.166"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015574"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015573"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2006.09.005"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3308"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31819ac71b"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0397-19.2019"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1038"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00052.2017"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12990-015-0063-9"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.072751"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0468-18.2018"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-71"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.048"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa993"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001846"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91620-9"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.11.047"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80966-6"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01665.x"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.64506"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.015"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71752"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky955"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.111"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_3_86_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini Y.","year":"1995","unstructured":"Y. Benjamini, Y. Hochberg, Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Statist. Soc. B 57, 289\u2013300 (1995).","journal-title":"J. R. Statist. Soc. B"},{"key":"e_1_3_3_87_2","first-page":"275","article-title":"False discovery rates: A new deal","volume":"18","author":"Stephens M.","year":"2017","unstructured":"M. Stephens, False discovery rates: A new deal. Biostatistics 18, 275\u2013294 (2017).","journal-title":"Biostatistics"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.abj8186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T15:47:00Z","timestamp":1726674420000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.abj8186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":86,"journal-issue":{"issue":"632","published-print":{"date-parts":[[2022,2,16]]}},"alternative-id":["10.1126\/scitranslmed.abj8186"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.abj8186","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,16]]},"article-number":"eabj8186"}}