Microglia polarization in nociplastic pain: mechanisms and perspectives

Atta, Ahd A.; Ibrahim, Weam W.; Mohamed, Abdullah; Abdelkader, Noha F.

doi:10.1007/s10787-023-01216-x

Cited by 38 publications

(20 citation statements)

References 122 publications

(128 reference statements)

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“…There was a more signi cant difference in the expression of in ammatory factors in in ammatory mice with 808 nm light combination treatment compared with LPS group. Different phenotype s of microglia release various factors and functions [26,43]. Treatment with 808-CM in cells and 808 nm light combined hUCMSCs treatment in in ammatory mice signi cantly inhibited TNF-α and IL-6 expression while promoting M2 phenotype polarization, promoted IL-10 expression, and improved learning and memory ability in in ammatory mice.…”

Section: Discussionmentioning

confidence: 99%

PBM Combined with hUCMSCs Modulates the Polarization of Microglia

Chen,

Zhu,

Cai

et al. 2024

Preprint

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Background Neuroinflammation occurs and develops in neurodegenerative diseases, and the severity of neuroinflammation is closely linked to microglial polarization. Different phenotypes release inflammatory cytokines and perform distinct functions. Modulating microglial polarization to alter neuroinflammation is a potential therapeutic strategy. Currently, human umbilical cord mesenchymal stem cells (hUCMSCs) possess multiple properties of stem cells and can be used in inflammation modulation therapy. Various methods of pre-treatment stem cells have been shown enhance efficacy in disease treatment. Photobiomodulation (PBM), as a non-invasive intervention, has the ability to reduce inflammation. Methods Firstly, we constructed a cellular inflammation model to investigate the effect of PBM pre-treatment of hUCMSCs on inflammation and polarization of BV2 cells. We also investigated the effect of the Notch signaling pathway on cells. Secondly, an animal inflammation model was constructed to verify that PBM pre-treatment of hUCMSCs modulated microglia polarization and neuroinflammation. Results In our in vitro experiments, PBM pre-treatment of hUCMSCs reduced the release of pro-inflammatory cytokines while promoting the expression of anti-inflammatory cytokine in microglia. The treatment significantly reduced the expression of Notch pathway-related genes in an inflammatory model, facilitated the reduction of M1 phenotype polarization and increased M2 phenotype polarization in microglia. In vivo studies demonstrated that 808 nm light combined with hUCMSCs improved memory behavior in male C57BL/6J mice and significantly reduced the release of pro-inflammatory cytokines in serum and brain tissue while promoting the expression of anti-inflammatory cytokine and the M2 phenotype polarization of microglia. Conclusions Overall, our results reveal that photobiomodulation with 808 nm light plays a crucial role in modulating microglial function through its interaction with hUCMSCs, providing novel insights into the molecular mechanism underlying microglial polarization.

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Section: Discussionmentioning

confidence: 99%

PBM Combined with hUCMSCs Modulates the Polarization of Microglia

Chen,

Zhu,

Cai

et al. 2024

Preprint

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“…The polarization of microglia towards the M1 phenotype is known as the classical activation pathway. Damage-induced cell debris, lipopolysaccharides (LPSs) derived from bacteria, and pro-inflammatory cytokines such as IL-1β and TNF-α can activate microglia and promote their polarization toward the M1 phenotype [32][33][34]. At this point, they begin to express unique surface markers such as cluster of differentiation (CD)14, CD16, CD32, CD80, and CD86.…”

Section: Phenotype Of Microgliamentioning

confidence: 99%

Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy

Cai,

Xia,

Zhang

2024

Antioxidants

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Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness among the working-age population. Microglia, resident immune cells in the retina, are recognized as crucial drivers in the DR process. Microglia activation is a tightly regulated immunometabolic process. In the early stages of DR, the M1 phenotype commonly shifts from oxidative phosphorylation to aerobic glycolysis for energy production. Emerging evidence suggests that microglia in DR not only engage specific metabolic pathways but also rearrange their oxidation-reduction (redox) system. This redox adaptation supports metabolic reprogramming and offers potential therapeutic strategies using antioxidants. Here, we provide an overview of recent insights into the involvement of reactive oxygen species and the distinct roles played by key cellular antioxidant pathways, including the NADPH oxidase 2 system, which promotes glycolysis via enhanced glucose transporter 4 translocation to the cell membrane through the AKT/mTOR pathway, as well as the involvement of the thioredoxin and nuclear factor E2-related factor 2 antioxidant systems, which maintain microglia in an anti-inflammatory state. Therefore, we highlight the potential for targeting the modulation of microglial redox metabolism to offer new concepts for DR treatment.

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“…This chemokine is produced by neurons in the spinal cord and DRGs after nerve injury, while its receptor, CX3CR1, is present on the surface of microglial cells and is highly upregulated during neuropathic pain development [8]. It is also known that the binding of CX3CR1 by CX3CL1 increases microglial proliferation and migration [197,198]. There is also evidence that ERK5, which is expressed by microglia, is necessary for CX3CL1/CX3CR1-induced microglial activation and the induction of hyperalgesia [199].…”

Section: Cx3c Chemokine In Neuropathic Painmentioning

confidence: 99%

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain

Pawlik

Mika

2023

Molecules

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Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients’ quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and maintenance of neuropathy but also in the effectiveness of analgesic drugs. Currently, approximately 50 chemokines are known to act through 20 different seven-transmembrane G-protein-coupled receptors located on the surface of neuronal, glial, and immune cells. Data from recent years clearly indicate that more chemokines than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) have pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting their synthesis, or blocking their receptors brings neuropathic pain relief. Several of them (CCL1/2/3/7/9/XCL1) have been shown to be able to reduce opioid drug effectiveness in neuropathy, and neutralizing antibodies against them can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence that chemokine receptors are promising targets for pharmacotherapy; chemokine receptor antagonists can relieve pain of different etiologies, and most of them are able to enhance opioid analgesia, for example, the blockade of CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), and XCR1 (vMIP-II). Recent research has shown that multitarget antagonists of chemokine receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), and CCR2/CCR5/CCR8 (RAP-103), are also very effective painkillers. A multidirectional strategy based on the modulation of neuronal–glial–immune interactions by changing the activity of the chemokine family can significantly improve the quality of life of patients suffering from neuropathic pain. However, members of the chemokine family are still underestimated pharmacological targets for pain treatment. In this article, we review the literature and provide new insights into the role of chemokines and their receptors in neuropathic pain.

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Microglia polarization in nociplastic pain: mechanisms and perspectives

Cited by 38 publications

References 122 publications

PBM Combined with hUCMSCs Modulates the Polarization of Microglia

PBM Combined with hUCMSCs Modulates the Polarization of Microglia

Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain

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