{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:27:24Z","timestamp":1790227644845,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prof. KH Ren\u00e9 Koczorek Stiftung","award":["439742772"],"award-info":[{"award-number":["439742772"]}]},{"name":"Prof. KH Ren\u00e9 Koczorek Stiftung","award":["01GQ2109A"],"award-info":[{"award-number":["01GQ2109A"]}]},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","award":["439742772"],"award-info":[{"award-number":["439742772"]}]},{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","award":["01GQ2109A"],"award-info":[{"award-number":["01GQ2109A"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["439742772"],"award-info":[{"award-number":["439742772"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["01GQ2109A"],"award-info":[{"award-number":["01GQ2109A"]}]},{"name":"Bundesministerium f\u00fcr Bildung und Forschung","award":["439742772"],"award-info":[{"award-number":["439742772"]}]},{"name":"Bundesministerium f\u00fcr Bildung und Forschung","award":["01GQ2109A"],"award-info":[{"award-number":["01GQ2109A"]}]},{"name":"DFG","award":["439742772"],"award-info":[{"award-number":["439742772"]}]},{"name":"DFG","award":["01GQ2109A"],"award-info":[{"award-number":["01GQ2109A"]}]},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","award":["439742772"],"award-info":[{"award-number":["439742772"]}]},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin","award":["01GQ2109A"],"award-info":[{"award-number":["01GQ2109A"]}]},{"name":"Berlin Institute of Health at Charit\u00e9 (BIH)","award":["439742772"],"award-info":[{"award-number":["439742772"]}]},{"name":"Berlin Institute of Health at Charit\u00e9 (BIH)","award":["01GQ2109A"],"award-info":[{"award-number":["01GQ2109A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The presence and function of the opioidergic system in sensory dorsal root ganglia (DRG) was demonstrated in various animal models of pain. To endorse recent functional and transcriptional evidence of opioid receptors in human DRG, this study compared morphological and transcriptional evidence in human and rat DRG using immunofluorescence confocal microscopy and mRNA transcript analysis. Specifically, it examined the neuronal expression of mu (MOR), delta (DOR), and kappa (KOR) opioid receptors, opioid peptide precursors (POMC, PENK, and PDYN), and key pain-signaling molecules. The results demonstrate abundant immunoreactivity in human DRG for key pain transduction receptors, including the thermosensitive ion channels TRPV1, TRPV4 and TRPA1, mechanosensitive PIEZO1 and PIEZO2, and the nociceptive-specific Nav1.8. They colocalized with calcitonin gene-related peptide (CGRP), a marker for peptidergic sensory neurons. Within this same subpopulation, we identified MOR, DOR, and KOR, while their ligand precursors were less abundant. Notably, the mRNA transcripts of MOR and PENK in human DRG were highest among the opioid-related genes; however, they were considerably lower than those of key pain-signaling molecules. These findings were corroborated by functional evidence in demonstrating the fentanyl-induced inhibition of voltage-gated calcium currents in rat DRG, which was antagonized by naloxone. The immunohistochemical and transcriptional demonstration of opioid receptors and their endogenous ligands in both human and rat DRG support recent electrophysiologic and in situ hybridization evidence in human DRG and confirms their potential as analgesic targets. This peripherally targeted approach has the advantage of mitigating central opioid-related side effects, endorsing the potential of future translational pain research from rodent models to humans.<\/jats:p>","DOI":"10.3390\/cells14100694","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T03:59:26Z","timestamp":1747108766000},"page":"694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Identification of Opioid Receptors and Peptide Precursors in Human DRG Neurons Expressing Pain-Signaling Molecules Confirms Their Potential as Analgesic Targets"],"prefix":"10.3390","volume":"14","author":[{"given":"Shaaban A.","family":"Mousa","sequence":"first","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Shaqura","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5623-8400","authenticated-orcid":false,"given":"Sascha","family":"Tafelski","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Mitte and Campus Virchow Clinic, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4470-6393","authenticated-orcid":false,"given":"Jan David","family":"Wandrey","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Mitte and Campus Virchow Clinic, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charit\u00e9 Digital Clinician Scientist Program, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-4964","authenticated-orcid":false,"given":"\u00d6zg\u00fcr","family":"Celik","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-7680","authenticated-orcid":false,"given":"Sascha","family":"Treskatsch","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1581-706X","authenticated-orcid":false,"given":"Michael","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Department of Anaesthesiology and Intensive Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1002\/j.1532-2149.2011.00070.x","article-title":"Relative contributions of peripheral versus supraspinal or spinal opioid receptors to the antinociception of systemic opioids","volume":"16","author":"Khalefa","year":"2012","journal-title":"Eur. J. Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1001\/jamasurg.2021.6210","article-title":"Current Issues in the Use of Opioids for the Management of Postoperative Pain: A Review","volume":"157","author":"Macintyre","year":"2022","journal-title":"JAMA Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"960389","DOI":"10.3389\/fpain.2023.960389","article-title":"The opioid receptor: Emergence through millennia of pharmaceutical sciences","volume":"4","author":"Fairbanks","year":"2023","journal-title":"Front. Pain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/nm908","article-title":"Attacking pain at its source: New perspectives on opioids","volume":"9","author":"Stein","year":"2003","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/SPC.0000000000000495","article-title":"Opioid analgesia: Recent developments","volume":"14","author":"Stein","year":"2020","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1056\/NEJM199110173251602","article-title":"Analgesic effect of intraarticular morphine after arthroscopic knee surgery","volume":"325","author":"Stein","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_7","first-page":"Cd008918","article-title":"Single dose intra-articular morphine for pain control after knee arthroscopy","volume":"2016","author":"Zou","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_8","first-page":"83","article-title":"No evidence for analgesic effect of intra-articular morphine after knee arthroscopy: A qualitative systematic review","volume":"30","author":"Rosseland","year":"2005","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0304-3959(97)03344-7","article-title":"Pain relief from intra-articular morphine after knee surgery: A qualitative systematic review","volume":"71","author":"Kalso","year":"1997","journal-title":"Pain"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Santino, F., and Gentilucci, L. (2023). Design of \u03ba-Opioid Receptor Agonists for the Development of Potential Treatments of Pain with Reduced Side Effects. Molecules, 28.","DOI":"10.3390\/molecules28010346"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/FBP.0000000000000558","article-title":"Peripherally acting opioid analgesics and peripherally-induced analgesia","volume":"31","author":"Abalo","year":"2020","journal-title":"Behav. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1097\/AJP.0b013e3181c49e3a","article-title":"Delta and kappa opioid receptors as suitable drug targets for pain","volume":"26","author":"Vanderah","year":"2010","journal-title":"Clin. J. Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/med.2610120505","article-title":"Opioid agonists and antagonists: An evaluation of their peripheral actions in inflammation","volume":"12","author":"Barber","year":"1992","journal-title":"Med. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114614","DOI":"10.1016\/j.celrep.2024.114614","article-title":"Analgesic targets identified in mouse sensory neuron somata and terminal pain translatomes","volume":"43","author":"Bangash","year":"2024","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"eadj9173","DOI":"10.1126\/sciadv.adj9173","article-title":"Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia","volume":"10","author":"Bhuiyan","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1111\/ejn.15733","article-title":"Distribution of delta and mu opioid receptor mRNA in rodent dorsal root ganglia neurons","volume":"56","author":"Quirion","year":"2022","journal-title":"Eur. J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1097\/j.pain.0000000000001973","article-title":"Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscope in situ hybridization","volume":"161","author":"Shiers","year":"2020","journal-title":"Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eabj8186","DOI":"10.1126\/scitranslmed.abj8186","article-title":"Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors","volume":"14","author":"Shiers","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1097\/j.pain.0000000000001217","article-title":"Comparative transcriptome profiling of the human and mouse dorsal root ganglia: An RNA-seq-based resource for pain and sensory neuroscience research","volume":"159","author":"Ray","year":"2018","journal-title":"Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1097\/j.pain.0000000000001846","article-title":"Distribution of functional opioid receptors in human dorsal root ganglion neurons","volume":"161","author":"Moy","year":"2020","journal-title":"Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101788","DOI":"10.1016\/j.xcrm.2024.101788","article-title":"The \u03bc-opioid receptor differentiates two distinct human nociceptive populations relevant to clinical pain","volume":"5","author":"Staedtler","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/j.neuron.2018.08.044","article-title":"Kappa Opioid Receptor Distribution and Function in Primary Afferents","volume":"99","author":"Snyder","year":"2018","journal-title":"Neuron"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tafelski, S., Wandrey, J.D., Shaqura, M., Hong, X., Beyer, A., Sch\u00e4fer, M., and Mousa, S.A. (2023). Translation of Experimental Findings from Animal to Human Biology: Identification of Neuronal Mineralocorticoid and Glucocorticoid Receptors in a Sectioned Main Nerve Trunk of the Leg. Cells, 12.","DOI":"10.3390\/cells12131785"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1002\/cne.22427","article-title":"Identification of mu- and kappa-opioid receptors as potential targets to regulate parasympathetic, sympathetic, and sensory neurons within rat intracardiac ganglia","volume":"518","author":"Mousa","year":"2010","journal-title":"J. Comp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/cne.22560","article-title":"Developmental expression of \u03b4-opioid receptors during maturation of the parasympathetic, sympathetic, and sensory innervations of the neonatal heart: Early targets for opioid regulation of autonomic control","volume":"519","author":"Mousa","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/cne.21982","article-title":"Coexpression of alpha 2A-adrenergic and delta-opioid receptors in substance P-containing terminals in rat dorsal horn","volume":"513","author":"Riedl","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0306-4522(97)00288-1","article-title":"Immunolocalization of two mu-opioid receptor isoforms (MOR1 and MOR1B) in the rat central nervous system","volume":"82","author":"Schulz","year":"1998","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/0306-4522(95)00464-5","article-title":"Immunohistochemical localization of the cloned kappa 1 receptor in the rat CNS and pituitary","volume":"71","author":"Mansour","year":"1996","journal-title":"Neuroscience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S1734-1140(10)70251-6","article-title":"Local pulmonary opioid network in patients with lung cancer: A putative modulator of respiratory function","volume":"62","author":"Krajnik","year":"2010","journal-title":"Pharmacol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1136\/ard.2006.067066","article-title":"Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis","volume":"66","author":"Mousa","year":"2007","journal-title":"Ann. Rheum. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1113\/JP272718","article-title":"Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces","volume":"595","author":"Wang","year":"2017","journal-title":"J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5092","DOI":"10.1523\/JNEUROSCI.1157-07.2007","article-title":"Beta-arrestin2 and c-Src regulate the constitutive activity and recycling of mu opioid receptors in dorsal root ganglion neurons","volume":"27","author":"Walwyn","year":"2007","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1124\/mol.106.026740","article-title":"Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain","volume":"71","author":"Heppenstall","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jconrel.2017.10.016","article-title":"Accessibility of axonal G protein coupled mu-opioid receptors requires conceptual changes of axonal membrane targeting for pain modulation","volume":"268","author":"Mousa","year":"2017","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Barry, A.M., Sondermann, J.R., Lesnak, J.B., Xian, F., Franco-Enz\u00e1stiga, \u00da., O\u2019Brien, J.A., Varela, D.G., Schackmuth, M.K., Shiers, S., and Price, T.J. (2024). Multi-omic integration with human DRG proteomics highlights TNF\u03b1 signalling as a relevant sexually dimorphic pathway. bioRxiv.","DOI":"10.1101\/2024.12.06.626968"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/brain\/awac266","article-title":"RNA profiling of human dorsal root ganglia reveals sex differences in mechanisms promoting neuropathic pain","volume":"146","author":"Ray","year":"2023","journal-title":"Brain A J. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/brain\/awz063","article-title":"Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons","volume":"142","author":"North","year":"2019","journal-title":"Brain A J. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Doty, M., Yun, S., Wang, Y., Hu, M., Cassidy, M., Hall, B., and Kulkarni, A.B. (2022). Integrative multiomic analyses of dorsal root ganglia in diabetic neuropathic pain using proteomics, phospho-proteomics, and metabolomics. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-21394-y"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41467-023-36014-0","article-title":"Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function","volume":"14","author":"Jung","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"71752","DOI":"10.7554\/eLife.71752","article-title":"Single-nucleus transcriptomic analysis of human dorsal root ganglion neurons","volume":"10","author":"Nguyen","year":"2021","journal-title":"Elife"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Schwaid, A.G., Krasowka-Zoladek, A., Chi, A., and Cornella-Taracido, I. (2018). Comparison of the Rat and Human Dorsal Root Ganglion Proteome. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31189-9"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.neuropharm.2014.05.026","article-title":"New insights into mechanisms of opioid inhibitory effects on capsaicin-induced TRPV1 activity during painful diabetic neuropathy","volume":"85","author":"Shaqura","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s12974-020-01864-8","article-title":"Neuronal aldosterone elicits a distinct genomic response in pain signaling molecules contributing to inflammatory pain","volume":"17","author":"Shaqura","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1111\/j.1460-9568.2004.03290.x","article-title":"Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa","volume":"19","author":"Schicho","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1097\/00001756-200112040-00018","article-title":"Vanilloid receptor homologue, VRL1, is expressed by both A- and C-fiber sensory neurons","volume":"12","author":"Ma","year":"2001","journal-title":"Neuroreport"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1744-8069-10-44","article-title":"Itch-associated peptides: RNA-Seq and bioinformatic analysis of natriuretic precursor peptide B and gastrin releasing peptide in dorsal root and trigeminal ganglia, and the spinal cord","volume":"10","author":"Goswami","year":"2014","journal-title":"Mol. Pain"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1002\/jcp.30096","article-title":"TRPV4 activity regulates nuclear Ca(2+) and transcriptional functions of \u03b2-catenin in a renal epithelial cell model","volume":"236","author":"Larre","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/9195","article-title":"The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways","volume":"2","author":"Akopian","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Weibel, R., Reiss, D., Karchewski, L., Gardon, O., Matifas, A., Filliol, D., Becker, J.A., Wood, J.N., Kieffer, B.L., and Gaveriaux-Ruff, C. (2013). Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: Insight from conditional knockout mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074706"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ceredig, R.A., Pierre, F., Doridot, S., Alduntzin, U., Hener, P., Salvat, E., Yalcin, I., Gaveriaux-Ruff, C., Barrot, M., and Massotte, D. (2019). Peripheral Delta Opioid Receptors Mediate Formoterol Anti-allodynic Effect in a Mouse Model of Neuropathic Pain. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00324"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Hovhannisyan, A.H., Son, H., Mecklenburg, J., Barba-Escobedo, P.A., Tram, M., Gomez, R., Shannonhouse, J., Zou, Y., Weldon, K., and Ruparel, S. (2021). Pituitary hormones are specifically expressed in trigeminal sensory neurons and contribute to pain responses in the trigeminal system. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-97084-y"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.jpain.2020.01.001","article-title":"Dynorphin and Enkephalin Opioid Peptides and Transcripts in Spinal Cord and Dorsal Root Ganglion During Peripheral Inflammatory Hyperalgesia and Allodynia","volume":"21","author":"Sapio","year":"2020","journal-title":"J. Pain Off. J. Am. Pain Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/164_2016_17","article-title":"Contribution of Delta-Opioid Receptors to Pathophysiological Events Explored by Endogenous Enkephalins","volume":"247","author":"Roques","year":"2018","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/0166-2236(92)90019-5","article-title":"Activity-dependent neuronal plasticity following tissue injury and inflammation","volume":"15","author":"Dubner","year":"1992","journal-title":"Trends Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/1096-9861(20010122)429:4<590::AID-CNE6>3.0.CO;2-V","article-title":"Equal proportions of small and large DRG neurons express opioid receptor mRNAs","volume":"429","author":"Wang","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"108131","DOI":"10.1016\/j.neuropharm.2020.108131","article-title":"Endogenous opioid peptides in the descending pain modulatory circuit","volume":"173","author":"Bagley","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1749-6632.2000.tb06673.x","article-title":"Spinal and supraspinal mechanisms of neuropathic pain","volume":"909","author":"Ossipov","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Celik, M., Seitz, V., Yerg\u00f6z, F., Dembla, S., Blum, N.K., Schulz, S., and Stein, C. (2023). Modulation of G-protein activation, calcium currents and opioid receptor phosphorylation by the pH-dependent antinociceptive agonist NFEPP. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1171855"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1152\/jn.1995.73.5.1793","article-title":"Interaction of opioids and membrane potential to modulate Ca2+ channels in rat dorsal root ganglion neurons","volume":"73","author":"Womack","year":"1995","journal-title":"J. Neurophysiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1213\/00000539-198712000-00013","article-title":"Opioid analgesia at peripheral sites: A target for opioids released during stress and inflammation?","volume":"66","author":"Joris","year":"1987","journal-title":"Anesth. Analg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0022-3565(25)24151-9","article-title":"Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors","volume":"248","author":"Stein","year":"1989","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Schmidhammer, H., Al-Khrasani, M., F\u00fcrst, S., and Spetea, M. (2023). Peripheralization Strategies Applied to Morphinans and Implications for Improved Treatment of Pain. Molecules, 28.","DOI":"10.3390\/molecules28124761"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1111\/aas.12529","article-title":"Peripherally applied opioids for postoperative pain: Evidence of an analgesic effect? A systematic review and meta-analysis","volume":"59","author":"Nielsen","year":"2015","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1126\/science.aai8636","article-title":"A nontoxic pain killer designed by modeling of pathological receptor conformations","volume":"355","author":"Spahn","year":"2017","journal-title":"Science"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/694\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:30:54Z","timestamp":1760031054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,11]]},"references-count":65,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cells14100694"],"URL":"https:\/\/doi.org\/10.3390\/cells14100694","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,11]]}}}