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The main pathophysiological mechanism for developing nociplastic pain is central sensitization (CS) in which pain amplification and hypersensitivity occur. Fibromyalgia is the prototypical nociplastic pain disorder, characterized by allodynia and hyperalgesia. Much scientific data suggest that classical activation of microglia in the spinal cord mediates neuroinflammation which plays an essential role in developing CS. In this review article, we discuss the impact of microglia activation and M1\/M2 polarization on developing neuroinflammation and nociplastic pain, besides the molecular mechanisms engaged in this process. In addition, we mention the impact of microglial modulators on M1\/M2 microglial polarization that offers a novel therapeutic alternative for the management of nociplastic pain disorders.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>\n                <jats:p>Illustrating the mechanisms underlying microglia activation in central sensitization and nociplastic pain. LPS lipopolysaccharide, TNF-\u03b1 tumor necrosis factor-\u03b1, INF-\u03b3 Interferon gamma, ATP adenosine triphosphate, 49 P2Y12\/13R purinergic P2Y 12\/13 receptor, P2X4\/7R purinergic P2X 4\/7 receptor, SP Substance P, NK-1R Neurokinin 1 receptor, CCL2 CC motif ligand 2, CCR2 CC motif ligand 2 receptor, CSF-1 colony-stimulating factor 1, CSF-1R colony-stimulating factor 1 receptor, CX3CL1 CX3C motif ligand 1, CX3XR1 CX3C motif ligand 1 receptor, TLR toll-like receptor, MAPK mitogen-activated protein kinases, JNK jun N-terminal kinase, ERK extracellular signal-regulated kinase, iNOS Inducible nitric oxide synthase, IL-1\u03b2 interleukin-1\u03b2, IL-6 interleukin-6, BDNF brain-derived neurotrophic factor, GABA \u03b3-Aminobutyric acid, GABAR \u03b3-Aminobutyric acid receptor, NMDAR N-methyl-D-aspartate receptor, AMPAR \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropi-onic acid receptor, IL-4 interleukin-4, IL-13 interleukin-13, IL-10 interleukin-10, Arg-1 Arginase 1, FGF fibroblast growth factor, GDNF glial cell-derived neurotrophic factor, IGF-1 insulin-like growth factor-1, NGF nerve growth factor, CD Cluster of differentiation.<\/jats:p>","DOI":"10.1007\/s10787-023-01216-x","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T16:02:29Z","timestamp":1681747349000},"page":"1053-1067","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":185,"title":["Microglia polarization in nociplastic pain: mechanisms and perspectives"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-3858","authenticated-orcid":false,"given":"Ahd A.","family":"Atta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weam W.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed F.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha F.","family":"Abdelkader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"1216_CR1","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/S12272-022-01391-5\/FIGURES\/1","volume":"45","author":"NF Abdelkader","year":"2022","unstructured":"Abdelkader NF, Elbaset MA, Moustafa PE, Ibrahim SM (2022) Empagliflozin mitigates type 2 diabetes-associated peripheral neuropathy: a glucose-independent effect through AMPK signaling. 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