{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:55:16Z","timestamp":1791312916593,"version":"4.3.1"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Economic Development, Sustainability, and Environment of the Basque Government"},{"id":[{"id":"https:\/\/ror.org\/00pz2fp31","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01rkhv978","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neuropathic pain (NP) is driven by neuroimmune interactions where in activated microglia release pro-inflammatory mediators that sustain central sensitization. Platelet-rich plasma (PRP) is a promising therapy, but its efficacy depends on its biochemical composition. This study aimed to evaluate how modifying the molecular profile of PRP influences its capacity to modulate neuroinflammation in a human-derived co-culture model. We compared standard PRP (sPRP) and balanced protein-concentrate plasma (BPCP), enriched in extraplatelet molecules, using an iPSC direct co-culture of sensory neurons (hSNs) and microglia (hMG). Neuroinflammation was induced for 24 h with serum-free (SF) or 10% sPRP or BPCP supplementation. Neuroinflammation, microglial activation, apoptosis, and neuronal plasticity were analyzed via RT-qPCR and Luminex. Both formulations attenuated pro-inflammatory mediators. However, BPCP demonstrated superior suppressive efficacy, reducing the levels of major cytokines (IL-1\u03b2, TNF-\u03b1, IL-6, IL-8) by half as compared to sPRP. BPCP significantly decreased IL-6, IL-8, and MCP-1 protein levels; kept microglial activation markers (CD86, CTSS) downregulated; and downregulated the apoptotic cascade (BAX, CASP9, CASP3). Conversely, sPRP displayed a distinct pro-resolving and neuroprotective trend, upregulating IL-10 and TGF-\u03b21 and rescuing the expression of SLC12A5 (KCC2), which regulates neuronal excitability. sPRP and BPCP modulated neuroinflammation via complementary mechanisms. BPCP acted as an immunomodulatory shield suppressing macro-inflammation, while sPRP drove inflammation resolution and neuroplastic rescue.<\/jats:p>","DOI":"10.3390\/ijms27167127","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:24:53Z","timestamp":1786353893000},"page":"7127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Platelet-Rich Plasma Modulates Neuroinflammation in an iPSC Model of Sensory Neurons and Microglia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9042-8841","authenticated-orcid":false,"given":"Jon","family":"Mercader-Ruiz","sequence":"first","affiliation":[{"name":"Advanced Biological Therapy Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1544-515X","authenticated-orcid":false,"given":"Daniel","family":"Marijuan-Pinel","sequence":"additional","affiliation":[{"name":"Advanced Biological Therapy Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-0804","authenticated-orcid":false,"given":"Diego","family":"Delgado","sequence":"additional","affiliation":[{"name":"Advanced Biological Therapy Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deiene","family":"Lasuen Aguirre","sequence":"additional","affiliation":[{"name":"Arthroscopic Surgery Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xabier","family":"Sansinanea","sequence":"additional","affiliation":[{"name":"Arthroscopic Surgery Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Guadilla","sequence":"additional","affiliation":[{"name":"Arthroscopic Surgery Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9992-6927","authenticated-orcid":false,"given":"Mikel","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Advanced Biological Therapy Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"},{"name":"Arthroscopic Surgery Unit, MiKS Hospital, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1152\/physrev.00045.2019","article-title":"Neuropathic Pain: From Mechanisms to Treatment","volume":"101","author":"Finnerup","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.euroneuro.2011.05.005","article-title":"Mechanisms of neuropathic pain","volume":"22","author":"Nickel","year":"2012","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Petroianu, G.A., Aloum, L., and Adem, A. (2023). Neuropathic pain: Mechanisms and therapeutic strategies. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1072629"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kaye, A.D., Armistead, G., Amedio, L.S., Manthei, M.E., Ahmadzadeh, S., Bernhardt, B., and Shekoohi, S. (2025). Evolving Treatment Strategies for Neuropathic Pain: A Narrative Review. Medicina, 61.","DOI":"10.3390\/medicina61061063"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.mehy.2009.08.034","article-title":"Migraine, neuropathic pain and nociceptive pain: Towards a unifying concept","volume":"74","author":"Chakravarty","year":"2010","journal-title":"Med. Hypotheses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2058738419838383","DOI":"10.1177\/2058738419838383","article-title":"The neuropathic pain: An overview of the current treatment and future therapeutic approaches","volume":"33","author":"Cavalli","year":"2019","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bja.2023.04.021","article-title":"Advances and challenges in neuropathic pain: A narrative review and future directions","volume":"131","author":"Attal","year":"2023","journal-title":"Br. J. Anaesth."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kocot-K\u0119pska, M., Zaj\u0105czkowska, R., Mika, J., Wordliczek, J., Dobrogowski, J., and Przeklasa-Muszy\u0144ska, A. (2021). Peripheral Mechanisms of Neuropathic Pain-the Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain. Pharmaceuticals, 14.","DOI":"10.3390\/ph14020077"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1515\/sjpain-2019-0138","article-title":"Role of the immune system in neuropathic pain","volume":"20","author":"Malcangio","year":"2019","journal-title":"Scand. J. Pain."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2868","DOI":"10.1002\/brb3.2868","article-title":"The core of maintaining neuropathic pain: Crosstalk between glial cells and neurons (neural cell crosstalk at spinal cord)","volume":"13","author":"Zhang","year":"2023","journal-title":"Brain Behav."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41583-025-00914-5","article-title":"How microglia contribute to the induction and maintenance of neuropathic pain","volume":"26","author":"Malcangio","year":"2025","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113614","DOI":"10.1016\/j.bcp.2019.08.016","article-title":"Microglia-neuron interactions in the models of neuropathic pain","volume":"169","author":"Tsuda","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/bja\/aex006","article-title":"The role of microglia in the pathobiology of neuropathic pain development: What do we know?","volume":"118","author":"Zhao","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/nrn.2018.2","article-title":"Microglia in neuropathic pain: Cellular and molecular mechanisms and therapeutic potential","volume":"19","author":"Inoue","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Boakye, P.A., Tang, S.-J., and Smith, P.A. (2021). Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-\u03b1, Wnt Ligands, and Interleukin 1\u03b2. Front. Pain. Res., 2.","DOI":"10.3389\/fpain.2021.698157"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1756-6606-4-31","article-title":"Neuronal and microglial mechanisms of neuropathic pain","volume":"4","author":"Zhuo","year":"2011","journal-title":"Mol. Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2480689","DOI":"10.1155\/2017\/2480689","article-title":"Neuronal-Glial Interactions Maintain Chronic Neuropathic Pain after Spinal Cord Injury","volume":"2017","author":"Gwak","year":"2017","journal-title":"Neural Plast."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1159\/000477353","article-title":"A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification","volume":"4","author":"Alves","year":"2018","journal-title":"Skin. Appendage Disord."},{"key":"ref_20","unstructured":"Cheng, B., and Fu, X. (2023). The Molecular Mechanisms of PRP on Cell Biological Function. Platelet-Rich Plasma in Tissue Repair and Regeneration: Technology and Transformation Application, Springer Nature."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/14712598.2017.1259409","article-title":"Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration","volume":"17","author":"Anitua","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, W.-S., Chen, L.-R., and Chen, K.-H. (2025). Platelet-Rich Plasma (PRP): Molecular Mechanisms, Actions and Clinical Applications in Human Body. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110804"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11420-011-9239-7","article-title":"The Role of Platelet-Rich Plasma in Inducing Musculoskeletal Tissue Healing","volume":"8","author":"Halpern","year":"2012","journal-title":"HSS J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez, M., Garate, A., Bilbao, A.M., Oraa, J., Yang\u00fcela, F., S\u00e1nchez, P., Guadilla, J., Aizpurua, B., Azofra, J., and Fiz, N. (2018). Platelet-Rich Plasma for Injured Peripheral Nerves: Biological Repair Process and Clinical Application Guidelines. Demystifying Polyneuropathy\u2014Recent Advances and New Directions, IntechOpen.","DOI":"10.5772\/intechopen.81104"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kuffler, D.P., and Foy, C.A. (2025). Mechanisms for reducing\/eliminating chronic neuropathic pain with a focus on platelet-rich plasma. Exp. Biol. Med., 250.","DOI":"10.3389\/ebm.2025.10567"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/ejp.1846","article-title":"Platelet-rich plasma and cytokines in neuropathic pain: A narrative review and a clinical perspective","volume":"26","author":"Bohren","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s12035-013-8494-7","article-title":"Platelet-Rich Plasma and the Elimination of Neuropathic Pain","volume":"48","author":"Kuffler","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yan, X., Ye, Y., Wang, L., Xue, J., Shen, N., and Li, T. (2024). Platelet-rich plasma alleviates neuropathic pain in osteoarthritis by downregulating microglial activation. BMC Musculoskelet. Disord., 25.","DOI":"10.1186\/s12891-024-07437-7"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ruzafa, N., Pereiro, X., Fonollosa, A., Araiz, J., Acera, A., and Vecino, E. (2021). The Effect of Plasma Rich in Growth Factors on Microglial Migration, Macroglial Gliosis and Proliferation, and Neuronal Survival. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.606232"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Shang, K., Liu, Y., and Qadeer, A. (2025). Platelet-rich plasma in peripheral nerve injury repair: A comprehensive review of mechanisms, clinical applications, and therapeutic potential. Exp. Biol. Med., 250.","DOI":"10.3389\/ebm.2025.10746"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, S., Liu, X., and Wang, Y. (2022). Evaluation of Platelet-Rich Plasma Therapy for Peripheral Nerve Regeneration: A Critical Review of Literature. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.808248"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.1038\/s41598-025-88918-0","article-title":"Increasing the concentration of plasma molecules improves the biological activity of platelet-rich plasma for tissue regeneration","volume":"15","author":"Fiz","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Beitia, M., Delgado, D., Mercader, J., S\u00e1nchez, P., L\u00f3pez de Dicastillo, L., and S\u00e1nchez, M. (2023). Action of Platelet-Rich Plasma on In Vitro Cellular Bioactivity: More than Platelets. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065367"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mercader Ruiz, J., Beitia, M., Delgado, D., S\u00e1nchez, P., Arnaiz, M.J., L\u00f3pez de Dicastillo, L., Benito-Lopez, F., Basabe-Desmonts, L., and S\u00e1nchez, M. (2023). New Formulation of Platelet-Rich Plasma Enriched in Platelet and Extraplatelet Biomolecules Using Hydrogels. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813811"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Everts, P.A., Lana, J.F., Alexander, R.W., Dallo, I., Kon, E., Ambach, M.A., van Zundert, A., and Podesta, L. (2024). Profound Properties of Protein-Rich, Platelet-Rich Plasma Matrices as Novel, Multi-Purpose Biological Platforms in Tissue Repair, Regeneration, and Wound Healing. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202405.1757.v1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1080\/14712598.2020.1798925","article-title":"Platelet-rich plasma for the treatment of knee osteoarthritis: An expert opinion and proposal for a novel classification and coding system","volume":"20","author":"Kon","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nm.4397","article-title":"Microglia emerge as central players in brain disease","volume":"23","author":"Salter","year":"2017","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.2147\/JPR.S246883","article-title":"The Role of Neuro-Immune Interactions in Chronic Pain: Implications for Clinical Practice","volume":"15","author":"Su","year":"2022","journal-title":"J. Pain Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/ALN.0000000000002130","article-title":"Neuroinflammation and Central Sensitization in Chronic and Widespread Pain","volume":"129","author":"Ji","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1097\/j.pain.0000000000001122","article-title":"Inflammation in the pathophysiology of neuropathic pain","volume":"159","author":"Sommer","year":"2018","journal-title":"Pain"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Batista, C.R.A., Gomes, G.F., Candelario-Jalil, E., Fiebich, B.L., and de Oliveira, A.C.P. (2019). Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092293"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13840","DOI":"10.1007\/s12035-025-05173-0","article-title":"The Efficacy of Intrathecal Platelet-Rich Plasma Administration in Alleviation of Chronic Neuropathic Pain in Rat Model","volume":"62","author":"Islam","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Labandeira-Garcia, J.L., Costa-Besada, M.A., Labandeira, C.M., Villar-Cheda, B., and Rodr\u00edguez-Perez, A.I. (2017). Insulin-Like Growth Factor-1 and Neuroinflammation. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00365"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"442","DOI":"10.37349\/ent.2024.00093","article-title":"Potentialities of IGF-1 for regulating oxidative stress in neuroinflammation and neurodegeneration: Theoretical review","volume":"4","author":"Herrera","year":"2024","journal-title":"Explor. Neuroprot Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"136575","DOI":"10.1016\/j.neulet.2022.136575","article-title":"Role of IGF-1 in neuroinflammation and cognition deficits induced by sleep deprivation","volume":"776","author":"Wan","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Desole, C., Gallo, S., Vitacolonna, A., Montarolo, F., Bertolotto, A., Vivien, D., Comoglio, P., and Crepaldi, T. (2021). HGF and MET: From Brain Development to Neurological Disorders. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.683609"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"155560","DOI":"10.1016\/j.cyto.2021.155560","article-title":"The regenerative mechanisms of platelet-rich plasma: A review","volume":"144","author":"Santos","year":"2021","journal-title":"Cytokine"},{"key":"ref_48","first-page":"557153","article-title":"Microglia Polarization: A Key Regulatory Mechanism of Neuropathic Pain","volume":"19","author":"Zhang","year":"2026","journal-title":"J. Pain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.tins.2023.05.001","article-title":"Microglial diversity in neuropathic pain","volume":"46","author":"Tsuda","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20140194","DOI":"10.1098\/rstb.2014.0194","article-title":"Regulation of neuronal excitability by release of proteins from glial cells","volume":"370","author":"Igelhorst","year":"2015","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41423-026-01438-3","article-title":"Microglia and neuroinflammation: Function, heterogeneity, and crosstalk","volume":"23","author":"Zong","year":"2026","journal-title":"Cell. Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Uchiyama, R., Toyoda, E., Maehara, M., Wasai, S., Omura, H., Watanabe, M., and Sato, M. (2021). Effect of Platelet-Rich Plasma on M1\/M2 Macrophage Polarization. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052336"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12805","DOI":"10.1038\/s41598-025-97501-6","article-title":"Platelet-rich plasma relieves inflammation and pain by regulating M1\/M2 macrophage polarization in knee osteoarthritis rats","volume":"15","author":"Xu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1007\/s12035-015-9251-x","article-title":"Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction","volume":"52","author":"Kuffler","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.immuni.2020.09.018","article-title":"Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge","volume":"53","author":"Shemer","year":"2020","journal-title":"Immunity"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Laffer, B., Bauer, D., Wasmuth, S., Busch, M., Jalilvand, T.V., Thanos, S., Meyer zu H\u00f6rste, G., Loser, K., Langmann, T., and Heiligenhaus, A. (2019). Loss of IL-10 Promotes Differentiation of Microglia to a M1 Phenotype. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00430"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbaexp.2005.08.005","article-title":"Role of nucleolin in posttranscriptional control of MMP-9 expression","volume":"1731","author":"Steege","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA)-Gene Struct. Expr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nm1723","article-title":"Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain","volume":"14","author":"Kawasaki","year":"2008","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1007\/s12035-016-9801-x","article-title":"Matrix Metalloproteinases During Axonal Regeneration, a Multifactorial Role from Start to Finish","volume":"54","author":"Andries","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ribeiro, H., Sarmento-Ribeiro, A.B., Andrade, J.P., and Dourado, M. (2022). Apoptosis and (in) Pain\u2014Potential Clinical Implications. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061255"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/imr.13275","article-title":"Stress\/cell death pathways, neuroinflammation, and neuropathic pain","volume":"321","author":"Li","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"20221051","DOI":"10.1515\/biol-2022-1051","article-title":"Neurodegenerative diseases and neuroinflammation-induced apoptosis","volume":"20","author":"Huang","year":"2025","journal-title":"Open Life Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/nature04223","article-title":"BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain","volume":"438","author":"Coull","year":"2005","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nature01786","article-title":"P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury","volume":"424","author":"Tsuda","year":"2003","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1093\/pm\/pnac066","article-title":"Injectable Biologics for Neuropathic Pain: A Systematic Review","volume":"23","author":"Bies","year":"2022","journal-title":"Pain Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:22:27Z","timestamp":1786422147000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":66,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167127"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167127","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]}}}