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This study tested whether the daily administration of fully characterized polyphenolic extracts from grape stalks and coffee could prevent both reflexive and non-reflexive chronic neuropathic pain in spinal cord-injured mice by modulating the neuroimmune axis. Female CD1 mice underwent mild spinal cord contusion and received intraperitoneal extracts in weeks one, three, and six post-surgery. Reflexive pain responses were assessed weekly for up to 10 weeks, and non-reflexive pain was evaluated at the study\u2019s end. Neuroimmune crosstalk was investigated, focusing on glial activation and the expression of CCL2\/CCR2 and CX3CL1\/CX3CR1 in supraspinal pain-related areas, including the periaqueductal gray, rostral ventromedial medulla, anterior cingulate cortex, and amygdala. Repeated treatments prevented mechanical allodynia and thermal hyperalgesia, and also modulated non-reflexive pain. Moreover, they reduced supraspinal gliosis and regulated CCL2\/CCR2 and CX3CL1\/CX3CR1 signaling. Overall, the combination of polyphenols in these extracts may offer a promising pharmacological strategy to prevent chronic reflexive and non-reflexive pain responses by modifying central sensitization markers, not only at the contusion site but also in key supraspinal regions implicated in neuropathic pain. Overall, these data highlight the potential of polyphenolic extracts for spinal cord injury-induced chronic neuropathic pain.<\/jats:p>","DOI":"10.3390\/ijms26073325","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T16:26:31Z","timestamp":1743611191000},"page":"3325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Repeated Administrations of Polyphenolic Extracts Prevent Chronic Reflexive and Non-Reflexive Neuropathic Pain Responses by Modulating Gliosis and CCL2-CCR2\/CX3CL1-CX3CR1 Signaling in Spinal Cord-Injured Female Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Anna","family":"Bag\u00f3-Mas","sequence":"first","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17071 Girona, Catalonia, Spain"},{"name":"Division of Neuroanatomy, Department of Anatomy, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Korimov\u00e1","sequence":"additional","affiliation":[{"name":"Division of Neuroanatomy, Department of Anatomy, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-126X","authenticated-orcid":false,"given":"Karol\u00edna","family":"Bretov\u00e1","sequence":"additional","affiliation":[{"name":"Division of Neuroanatomy, Department of Anatomy, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"Deulofeu","sequence":"additional","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17071 Girona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-1146","authenticated-orcid":false,"given":"Enrique","family":"Verd\u00fa","sequence":"additional","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17071 Girona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-6813","authenticated-orcid":false,"given":"N\u00faria","family":"Fiol","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Agriculture and Food Technology, Polytechnic School, University of Girona, 17003 Girona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8978-6596","authenticated-orcid":false,"given":"Petr","family":"Dubov\u00fd","sequence":"additional","affiliation":[{"name":"Division of Neuroanatomy, Department of Anatomy, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8497-1207","authenticated-orcid":false,"given":"Pere","family":"Boadas-Vaello","sequence":"additional","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17071 Girona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alizadeh, A., Dyck, S.M., and Karimi-Abdolrezaee, S. 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