The contribution of neuro-immune crosstalk to pain in the peripheral nervous system and the spinal cord

Gao, Yinping; Mei, Changqing; Chen, Pan; Chen, Xiaowei

doi:10.1016/j.intimp.2022.108700

Cited by 17 publications

(11 citation statements)

References 104 publications

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“…Consistently, our findings of increased levels of pro-inflammatory factors in the spinal cord and activation of glia confirmed the previous conclusion. Immune cells play a critical role in promoting neuroinflammation and development of pain [41][42][43]. The number of T cells was found elevated in mouse spinal cord after 48-h SR, [44], or stimulate the progression of bone cancer pain (unpublished data in our research group).…”

Section: Discussionmentioning

confidence: 99%

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia

Huang,

Xu,

Liu

et al. 2024

BMC Med

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Background Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously. Methods The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration. Results The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro. Conclusions Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.

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Section: Discussionmentioning

confidence: 99%

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia

Huang,

Xu,

Liu

et al. 2024

BMC Med

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“…Activated immune cells such as macrophages, neutrophils, and lymphocytes can release cytokines and chemokines that typically induce pain [ 57 ]. Pain can also induce immunity and help sensitize nociceptors [ 58 ]. Consistently, we found that, in CIPN rats, there was a meaningful correlation between overlapping mRNAs and many immune cells.…”

Section: Discussionmentioning

confidence: 99%

Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy

Cao

Wang

et al. 2023

CIMB

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Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA–miRNA–mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. Cdh1, Satb2, Fas, P2ry2, and Zfhx2 were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research.

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“…Sensory neurons detect damage in the skin or mucosal tissues and may release a variety of neuropeptides and neurotransmitters 105 that can communicate with immune cells. 106 This release by sensory, autonomic, and enteric neurons can contribute to wound healing by activating mast cells, recruiting immune mediators, fibroblasts, and promoting angiogenesis in large scale wounds. [107][108][109] Loss of appropriate innervation of the skin, as in diabetic neuropathy, can impair wound healing and prolong inflammation.…”

Section: Helminth Clearance Is Regulated By Neuroendocrine Cells Neur...mentioning

confidence: 99%

“Every cell is an immune cell; contributions of non-hematopoietic cells to anti-helminth immunity”

Rossi

Herbert

2022

Mucosal Immunology

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Helminths are remarkably successful parasites that can invade various mammalian hosts and establish chronic infections that can go unnoticed for years despite causing severe tissue damage. To complete their life cycles, helminths migrate through multiple barrier sites that are densely populated by a complex array of hematopoietic and non-hematopoietic cells. While it is clear that type 2 cytokine responses elicited by immune cells promote worm clearance and tissue healing, the actions of non-hematopoietic cells are increasingly recognized as initiators, effectors and regulators of anti-helminth immunity. This review will highlight the collective actions of specialized epithelial cells, stromal niches, stem, muscle and neuroendocrine cells as well as peripheral neurons in the detection and elimination of helminths at mucosal sites. Studies dissecting the interactions between immune and nonhematopoietic cells will truly provide a better understanding of the mechanisms that ensure homeostasis in the context of helminth infections.

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The contribution of neuro-immune crosstalk to pain in the peripheral nervous system and the spinal cord

Cited by 17 publications

References 104 publications

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia

Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy

“Every cell is an immune cell; contributions of non-hematopoietic cells to anti-helminth immunity”

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