The DOI matches its Crossref record; 120 of the 120 references it cites were found in a registry or an index.
Microglia polarization in nociplastic pain: mechanisms and perspectives
Open accessAbstract
Nociplastic pain is the third classification of pain as described by the International Association for the Study of Pain (IASP), in addition to the neuropathic and nociceptive pain classes. 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. Graphical abstract Illustrating the mechanisms underlying microglia activation in central sensitization and nociplastic pain. LPS lipopolysaccharide, TNF-α tumor necrosis factor-α, INF-γ 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-1β interleukin-1β, IL-6 interleukin-6, BDNF brain-derived neurotrophic factor, GABA γ-Aminobutyric acid, GABAR γ-Aminobutyric acid receptor, NMDAR N-methyl-D-aspartate receptor, AMPAR α-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.
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“In addition to activation, the polarization of central glial cells has also been reported to contribute to NPP pathogenesis of NPP (119).”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [119]
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1 retracted
Cordaro, M., Siracusa, R., D’Amico, R., Genovese, T., Franco, G., Marino, Y., Di Paola, D., Cuzzocrea, S., Impellizzeri, D., Di Paola, R., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116139 · Cited by 29
RetractedResting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
Raja, S. N., Carr, D. B., Cohen, M., Finnerup, N. B., Flor, H., Gibson, S., Keefe, F. J., Mogil, J. S., Ringkamp, M., Sluka, K. A., et al. (2020) · Pain · doi:10.1097/j.pain.0000000000001939 · Cited by 5,223
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Colloca, L., Ludman, T., Bouhassira, D., Baron, R., Dickenson, A. H., Yarnitsky, D., Freeman, R. L., Truini, A., Attal, N., Finnerup, N. B., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.2 · Cited by 2,271
Breivik, H., Borchgrevink, P. C., Allen, S. M., Rosseland, L. A., Romundstad, L., Breivik Hals, E. K., Kvarstein, G., & Stubhaug, A. (2008) · British Journal of Anaesthesia · doi:10.1093/bja/aen103 · Cited by 2,108
Neuropathic Pain: From Mechanisms to Treatment
Finnerup, N. B., Kuner, R., & Jensen, T. S. (2020) · Physiological Reviews · doi:10.1152/physrev.00045.2019 · Cited by 1,727
Fibromyalgia: A Clinical Review
Clauw, D. J. (2014) · JAMA · doi:10.1001/jama.2014.3266 · Cited by 1,674
Neuroinflammation and Central Sensitization in Chronic and Widespread Pain
Ji, R.-R., Nackley, A., Huh, Y., Terrando, N., & Maixner, W. (2018) · Anesthesiology · doi:10.1097/aln.0000000000002130 · Cited by 1,630
Nociplastic pain: towards an understanding of prevalent pain conditions
Fitzcharles, M.-A., Cohen, S. P., Clauw, D. J., Littlejohn, G., Usui, C., & Häuser, W. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00392-5 · Cited by 1,253
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Müller, L., Benedetto, S. D., & Müller, V. (2025) · Cells · doi:10.3390/cells14010054 · Cited by 102
Brain-Derived Neurotrophic Factor, Nociception, and Pain
Merighi, A. (2024) · Biomolecules · doi:10.3390/biom14050539 · Cited by 58
Sun, C., Deng, J., Ma, Y., Meng, F., Cui, X., Li, M., Li, J., Li, J., Yin, P., Kong, L., et al. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114570 · Cited by 44
Li, Z., Li, M., Fang, Z. H., & Wang, H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178336 · Cited by 47
Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain
Pawlik, K., & Mika, J. (2023) · Molecules · doi:10.3390/molecules28155766 · Cited by 45
Metadata
- Authors
- Atta, A. A., Ibrahim, W. W., Mohamed, A. F., & Abdelkader, N. F.
- Affiliations
- Cairo University (EG)
- Corresponding author
- Atta, Ahd A.
- Venue
- Inflammopharmacology
- Published
- 2023-04-17
- Volume
- 31
- Issue
- 3
- Pages
- 1053-1067
- ISSN
- 0925-4692 (ISSN-L)
- 1568-5608
- PMC
- PMC10229465
- OpenAlex
- W4366162633
- Cited by
- 178
- References
- 120
- Citations by year
- 2026: 62 · 2025: 67 · 2024: 38 · 2023: 11
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Inflammopharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Greater South Information System
- Funders
- Cairo University
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Keywords
- nociplastic pain, microglial polarization, M1/M2 microglia, central sensitization, neuroinflammation, fibromyalgia, spinal cord, purinergic receptors, substance P, CCL2/CCR2, CSF1R, CX3CL1/CX3CR1, Toll-like receptors, MAPK signaling, inducible nitric oxide synthase, brain-derived neurotrophic factor, GABA receptors, NMDA receptor, AMPA receptors, therapeutic target, allodynia, hyperalgesia
- MeSH terms
- Neuroinflammatory Diseases, Humans, Hyperalgesia, Ligands, Lipopolysaccharides, Pain, Tumor Necrosis Factor-alpha, Interleukin-6, Macrophage Colony-Stimulating Factor, Microglia
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