{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:27:31Z","timestamp":1786955251646,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Anesthesiology and Critical Care Medicine Research Endowment"},{"id":[{"id":"https:\/\/ror.org\/0229evh14","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence","award":["P20GM121176"],"award-info":[{"award-number":["P20GM121176"]}]},{"award":["P20GM121176"],"award-info":[{"award-number":["P20GM121176"]}],"id":[{"id":"https:\/\/ror.org\/05xkqnm68","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Primary sensory neurons of the dorsal root ganglion (DRG) express mu-type opioid receptors and undergo plasticity that can contribute to both analgesia and maladaptive outcomes such as opioid tolerance and opioid-induced hyperalgesia. Most mechanistic work has relied on rodent models, which may not fully capture the repertoire of opioid-responsive pathways present in humans. In this study, we tested whether morphine exposure reshapes gene expression programs in human nociceptors. Human induced pluripotent stem cell (hiPSC)-derived nociceptors were exposed to morphine (3.5 \u03bcM) acutely (1h, 16h) or repeatedly (2\u20133 days; daily 16h exposure separated by 8h washout) and profiled by time-series RNA sequencing. The transcriptional response to morphine included the induction of a small set of genes across exposure paradigms. P2RY11, encoding the purinergic G protein-coupled receptor P2Y11, was the most robustly induced transcript across the time course, and genes involved in purinergic signaling pathways exhibited coordinated expression dynamics. Since P2RY11 lacks a mouse\/rat ortholog, its contribution to nociceptor biology and opioid responses has remained largely underexplored. Using human DRG tissue and primary human DRG cultures from organ donors, we detected P2RY11 mRNA and P2Y11 protein in neuronal populations. We observed increased P2Y11 expression in peripherin-positive neurons after morphine exposure in vitro, corroborating our sequencing results. These findings identify P2RY11\/P2Y11 as a morphine-responsive purinergic receptor in DRG neurons and nominate purinergic signaling as a candidate pathway contributing to opioid-driven peripheral plasticity.<\/jats:p>","DOI":"10.3390\/cells15161464","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:05:41Z","timestamp":1786953941000},"page":"1464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Opioid Exposure Induces the Expression of the Purinergic Receptor P2RY11 in Human Nociceptors"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-9442","authenticated-orcid":false,"given":"Jenna B.","family":"Demeter","sequence":"first","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean D.","family":"McNally","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddy R.","family":"Koch","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9770-4628","authenticated-orcid":false,"given":"Sherwin","family":"Thiyagarajan","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette A.","family":"Montoya","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Vega","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0990-5779","authenticated-orcid":false,"given":"Paul","family":"Abboud","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-8950","authenticated-orcid":false,"given":"Sascha R. A.","family":"Alles","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Ehsanian","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-7595","authenticated-orcid":false,"given":"June Bryan I.","family":"de la Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Translational Pain Group, Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00789","DOI":"10.1002\/prp2.789","article-title":"Addressing Opioid Tolerance and Opioid-induced Hypersensitivity: Recent Developments and Future Therapeutic Strategies","volume":"9","author":"Khan","year":"2021","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1208\/s12248-008-9056-1","article-title":"Opioid Tolerance Development: A Pharmacokinetic\/Pharmacodynamic Perspective","volume":"10","author":"Dumas","year":"2008","journal-title":"AAPS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.36076\/ppj.2011\/14\/145","article-title":"A Comprehensive Review of Opioid-Induced Hyperalgesia","volume":"14","author":"Lee","year":"2011","journal-title":"Pain Physician"},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"7061","DOI":"10.1523\/JNEUROSCI.1191-19.2019","article-title":"In Vitro Nociceptor Neuroplasticity Associated with In Vivo Opioid-Induced Hyperalgesia","volume":"39","author":"Khomula","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e71752","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_7","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_8","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_9","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/brain\/awab048","article-title":"Studying Human Nociceptors: From Fundamentals to Clinic","volume":"144","author":"Middleton","year":"2021","journal-title":"Brain J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/toxsci\/kfac045","article-title":"In Vitro Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array","volume":"188","author":"Odawara","year":"2022","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104451","DOI":"10.1016\/j.jpain.2023.12.008","article-title":"Electrophysiological Analyses of Human Dorsal Root Ganglia and Human Induced Pluripotent Stem Cell-Derived Sensory Neurons from Male and Female Donors","volume":"25","author":"Zurek","year":"2023","journal-title":"J. Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109503","DOI":"10.1016\/j.neuropharm.2023.109503","article-title":"New Paradigms in Purinergic Receptor Ligand Discovery","volume":"230","author":"Jacobson","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11302-004-4740-9","article-title":"P2Y Receptors and Pain Transmission","volume":"1","author":"Gerevich","year":"2004","journal-title":"Purinergic Signal."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tozaki-Saitoh, H., Takeda, H., and Inoue, K. (2022). The Role of Microglial Purinergic Receptors in Pain Signaling. Molecules, 27.","DOI":"10.3390\/molecules27061919"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pbb.2014.11.001","article-title":"Participation of Peripheral P2Y1, P2Y6 and P2Y11 Receptors in Formalin-Induced Inflammatory Pain in Rats","volume":"128","year":"2015","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_16","first-page":"29","article-title":"Role of Spinal P2Y6 and P2Y11 Receptors in Neuropathic Pain in Rats: Possible Involvement of Glial Cells","volume":"10","year":"2014","journal-title":"Mol. Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nn.3295","article-title":"Morphine Hyperalgesia Gated through Microglia-Mediated Disruption of Neuronal Cl\u2212 Homeostasis","volume":"16","author":"Ferrini","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.pain.2010.02.042","article-title":"Inhibition of Microglial P2X4 Receptors Attenuates Morphine Tolerance, Iba1, GFAP and Mu Opioid Receptor Protein Expression While Enhancing Perivascular Microglial ED2","volume":"150","author":"Horvath","year":"2010","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10154","DOI":"10.1523\/JNEUROSCI.0852-17.2017","article-title":"Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance","volume":"37","author":"Weilinger","year":"2017","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s11302-016-9514-7","article-title":"A Critical Look at the Function of the P2Y11 Receptor","volume":"12","author":"Dreisig","year":"2016","journal-title":"Purinergic Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1111\/bph.15379","article-title":"The Human G Protein-Coupled ATP Receptor P2Y11 Is a Target for Anti-Inflammatory Strategies","volume":"178","author":"Gruenbacher","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","first-page":"8544","article-title":"Inhibition of Neutrophil Apoptosis by ATP Is Mediated by the P2Y11 Receptor","volume":"179","author":"Vaughan","year":"2007","journal-title":"J. Immunol. Baltim. Md"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Al-Abbasi, Z., Bhuiyan, S.A., Renthal, W., and Molliver, D.C. (2025). A Transcriptomic Comparison of the HD10.6 Human Sensory Neuron-Derived Cell Line with Primary and iPSC Sensory Neurons. bioRxiv, bioRxiv:2025.04.03.643725.","DOI":"10.1101\/2025.04.03.643725"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"174007","DOI":"10.1016\/j.ejphar.2021.174007","article-title":"Role of \u03b2-Arrestin-2 in Short- and Long-Term Opioid Tolerance in the Dorsal Root Ganglia","volume":"899","author":"Muchhala","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1124\/jpet.109.151704","article-title":"Sustained Morphine Treatment Augments Capsaicin-Evoked Calcitonin Gene-Related Peptide Release from Primary Sensory Neurons in a Protein Kinase A- and Raf-1-Dependent Manner","volume":"330","author":"Tumati","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ejphar.2008.02.013","article-title":"Sustained Morphine Treatment Augments Basal CGRP Release from Cultured Primary Sensory Neurons in a Raf-1 Dependent Manner","volume":"584","author":"Yue","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1046\/j.0953-816x.2001.01731.x","article-title":"Chronic Morphine Exposure Increases the Phosphorylation of MAP Kinases and the Transcription Factor CREB in Dorsal Root Ganglion Neurons: An In Vitro and In Vivo Study","volume":"14","author":"Ma","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1124\/jpet.118.252494","article-title":"Inhibitory Effects of Mas-Related Gene C Receptor on Chronic Morphine-Induced Spinal Glial Activation in Rats","volume":"368","author":"Zhang","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6167","DOI":"10.1038\/s41467-024-50420-y","article-title":"A Real-World Multi-Center RNA-Seq Benchmarking Study Using the Quartet and MAQC Reference Materials","volume":"15","author":"Wang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-Based Genome Alignment and Genotyping with HISAT2 and HISAT-Genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"StringTie Enables Improved Reconstruction of a Transcriptome from RNA-Seq Reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1093\/bioinformatics\/bti525","article-title":"BioMart and Bioconductor: A Powerful Link between Biological Databases and Microarray Data Analysis","volume":"21","author":"Durinck","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping Identifiers for the Integration of Genomic Datasets with the R\/Bioconductor Package biomaRt","volume":"4","author":"Durinck","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"gkaf018","DOI":"10.1093\/nar\/gkaf018","article-title":"edgeR v4: Powerful Differential Analysis of Sequencing Data with Expanded Functionality and Improved Support for Small Counts and Larger Datasets","volume":"53","author":"Chen","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R Package for Comparing Biological Themes among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics J. Integr. Biol."},{"key":"ref_36","first-page":"e119","article-title":"Impulse Model-Based Differential Expression Analysis of Time Course Sequencing Data","volume":"46","author":"Fischer","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lesnak, J.B., Schaub, M.K., Gomez, K., Calderon-Rivera, A., Loya-Lopez, S., Stewart, R., Jo, S., Fujita, A., Osorno, T., and Desai, M. (2025). Enabling Wider Access to Human Molecular Neuroscience Research in Pain: A Simple Preservation Method for Human Dorsal Root Ganglion Neurons in Hibernate A Media. bioRxiv, bioRxiv:2025.09.06.674648.","DOI":"10.2139\/ssrn.5499728"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Saad Yousuf, M., Mwirigi, J., Mancilla Moreno, M., Schackmuth, M., and Price, T. (2024). Dissociating and Culturing Human Dorsal Root Ganglia Neurons V1. Protocols.io.","DOI":"10.17504\/protocols.io.kxygxyd64l8j\/v1"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1097\/j.pain.0000000000002860","article-title":"Emergence of Nociceptive Functionality and Opioid Signaling in Human Induced Pluripotent Stem Cell-Derived Sensory Neurons","volume":"164","author":"Belu","year":"2023","journal-title":"Pain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0306-4522(00)00226-8","article-title":"Morphine Treatment Induced Calcitonin Gene-Related Peptide and Substance P Increases in Cultured Dorsal Root Ganglion Neurons","volume":"99","author":"Ma","year":"2000","journal-title":"Neuroscience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2165\/00003088-198207030-00006","article-title":"Patient-Controlled Analgesic Therapy, Part IV: Pharmacokinetics and Analgesic Plasma Concentrations of Morphine","volume":"7","author":"Tamsen","year":"1982","journal-title":"Clin. Pharmacokinet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/BF00609900","article-title":"Steady-State Kinetics and Analgesic Effect of Oral Morphine in Cancer Patients","volume":"24","author":"Rane","year":"1983","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_44","first-page":"592","article-title":"Pharmacokinetic Modelling of Morphine, Morphine-3-Glucuronide and Morphine-6-Glucuronide in Plasma and Cerebrospinal Fluid of Neurosurgical Patients after Short-Term Infusion of Morphine","volume":"54","author":"Meineke","year":"2002","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/cpt197517131","article-title":"Morphine Binding to Human Plasma Proteins","volume":"17","author":"Olsen","year":"1975","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s40262-016-0471-7","article-title":"A Prospective Population Pharmacokinetic Study on Morphine Metabolism in Cancer Patients","volume":"56","author":"Oosten","year":"2017","journal-title":"Clin. Pharmacokinet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF00265969","article-title":"Plasma Levels of Morphine and Morphine Glucuronides in the Treatment of Cancer Pain: Relationship to Renal Function and Route of Administration","volume":"38","author":"Peterson","year":"1990","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/head.12552","article-title":"Opioid-Induced Central Immune Signaling: Implications for Opioid Analgesia","volume":"55","author":"Grace","year":"2015","journal-title":"Headache"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/bs.apha.2015.09.001","article-title":"Purinergic Mechanisms and Pain","volume":"75","author":"Burnstock","year":"2016","journal-title":"Adv. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.2174\/138161209788186335","article-title":"Purinergic Receptors and Pain","volume":"15","author":"Burnstock","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17448069251376200","DOI":"10.1177\/17448069251376200","article-title":"Humanized Anti-P2X4 scFv Reduces ATP-Induced P2X4 Currents and Modulates Excitability in Human DRG Neurons","volume":"21","author":"Zurek","year":"2025","journal-title":"Mol. Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31969","DOI":"10.1074\/jbc.272.51.31969","article-title":"Cloning of a Human Purinergic P2Y Receptor Coupled to Phospholipase C and Adenylyl Cyclase","volume":"272","author":"Communi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/sj.bjp.0702909","article-title":"Pharmacological Characterization of the Human P2Y11 Receptor","volume":"128","author":"Communi","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7172","DOI":"10.4049\/jimmunol.166.12.7172","article-title":"The P2Y11 Receptor Mediates the ATP-Induced Maturation of Human Monocyte-Derived Dendritic Cells","volume":"166","author":"Wilkin","year":"2001","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Sakaki, H., Tsukimoto, M., Harada, H., Moriyama, Y., and Kojima, S. (2013). Autocrine Regulation of Macrophage Activation via Exocytosis of ATP and Activation of P2Y11 Receptor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059778"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Layhadi, J.A., and Fountain, S.J. (2019). ATP-Evoked Intracellular Ca2+ Responses in M-CSF Differentiated Human Monocyte-Derived Macrophage Are Mediated by P2X4 and P2Y11 Receptor Activation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205113"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"eaba3300","DOI":"10.1126\/scisignal.aba3300","article-title":"The Purinergic Receptor P2Y11 Choreographs the Polarization, Mitochondrial Metabolism, and Migration of T Lymphocytes","volume":"13","author":"Ledderose","year":"2020","journal-title":"Sci. Signal."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"32602","DOI":"10.1038\/srep32602","article-title":"Activation of P2X7 and P2Y11 Purinergic Receptors Inhibits Migration and Normalizes Tumor-Derived Endothelial Cells via cAMP Signaling","volume":"6","author":"Avanzato","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1248\/bpb.b18-00075","article-title":"A Novel Mechanism of \u03b3-Irradiation-Induced IL-6 Production Mediated by P2Y11 Receptor in Epidermal Keratinocytes","volume":"41","author":"Ohsaki","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gruenbacher, G., Gander, H., Rahm, A., Dobler, G., Drasche, A., Troppmair, J., Nussbaumer, W., and Thurnher, M. (2019). The Human G Protein-Coupled ATP Receptor P2Y11 Is Associated with IL-10 Driven Macrophage Differentiation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01870"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00018-022-04548-z","article-title":"The P2Y11 Receptor of Human M2 Macrophages Activates Canonical and IL-1 Receptor Signaling to Translate the Extracellular Danger Signal ATP into Anti-Inflammatory and pro-Angiogenic Responses","volume":"79","author":"Klaver","year":"2022","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s11302-023-09932-3","article-title":"P2Y11\/IL-1 Receptor Crosstalk Controls Macrophage Inflammation: A Novel Target for Anti-Inflammatory Strategies?","volume":"19","author":"Klaver","year":"2023","journal-title":"Purinergic Signal."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s11302-008-9106-2","article-title":"Development of Selective Agonists and Antagonists of P2Y Receptors","volume":"5","author":"Jacobson","year":"2009","journal-title":"Purinergic Signal."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/bs.irn.2024.10.003","article-title":"Modeling Neuropathic Pain in a Dish","volume":"179","author":"Zebochin","year":"2024","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yu, H., Usoskin, D., Nagi, S.S., Hu, Y., Kupari, J., Bouchatta, O., Cranfill, S.L., Gautam, M., Su, Y., and Lu, Y. (2023). Single-Soma Deep RNA Sequencing of Human DRG Neurons Reveals Novel Molecular and Cellular Mechanisms Underlying Somatosensation. bioRxiv, bioRxiv:2023.03.17.533207.","DOI":"10.2139\/ssrn.4399558"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"100216","DOI":"10.1016\/j.ynpai.2026.100216","article-title":"Transcriptomic Analysis and High Throughput Functional Characterization of Human Induced Pluripotent Stem Cell Derived Sensory Neurons","volume":"20","author":"Truong","year":"2026","journal-title":"Neurobiol. Pain"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Dedek, A., Alles, S.R.A., and Hildebrand, M.E. (2026). Electrophysiological Analysis of Human Pain-Processing Cells and Circuits. Anesth. Analg., Epub ahead of printing.","DOI":"10.1213\/ANE.0000000000008145"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1464\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:19:38Z","timestamp":1786954778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":67,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15161464"],"URL":"https:\/\/doi.org\/10.3390\/cells15161464","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,15]]}}}