Cited by 178Pain Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsFibromyalgia and Chronic Fatigue Syndrome Research

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Microglia polarization in nociplastic pain: mechanisms and perspectives

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Atta, Ahd A., Ibrahim, Weam W., Mohamed, Ahmed F., Abdelkader, Noha F.·2023·Inflammopharmacology

DOI 10.1007/s10787-023-01216-xPMC PMC10229465

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Abstract

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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Authors: Atta, A. A., Ibrahim, W. W., Mohamed, A. F., & Abdelkader, N. F.
Affiliations: Cairo University (EG)
Corresponding author: Atta, Ahd A.
ORCID: Atta, Ahd A.
Ibrahim, Weam W.
Abdelkader, Noha F.
Venue: Inflammopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2023-04-17
Volume: 31
Issue: 3
Pages: 1053-1067
ISSN: 0925-4692 (ISSN-L)
1568-5608
DOI: 10.1007/s10787-023-01216-x
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
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
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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Microglia polarization in nociplastic pain: mechanisms and perspectives

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