Electroacupuncture regulates microglia activation through theSTING/NF-κB pathway to reduce pain in bone cancer pain mouse DOI Creative Commons
英郎 螺良, Wenhao Liu,

Zhiyi Shen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Abstract Cancer pain is a global public health problem. The mechanism of cancer complex, and opioid analgesics, which are widely used clinically, have obvious addiction side effects, seriously affect patients’life functions may aggravate their anxiety, depression other negative emotions. Acupuncture has history thousands years in China, acupuncture analgesia been confirmed by many studies. This study investigated whether electroacupuncture can alleviate abnormal bone (BCP) mouse models its possible central mechanism. A model was established injecting Lewis lung cells into the left femoral cavity adult male mice. Mechanical paw withdrawal threshold tested baseline before surgery 1, 4, 7, 10, 14 21 days after surgery. On day 21, behaviours related to emotions were tested. After behaviours, femurs removed observe pathological changes, neck broken brain tissue collected from basal lateral amygdala (BLA) area for subsequent Western Blot ELISA experiments performed verify expression (stimulator interferon genes, STING) STING/NF- κ B pathway proteins inflammatory factors. Immunofluorescence Ionized calcium-binding adapter molecule-1 (Iba-1) STING region also performed. results show that increase depressive-like emotional phenotype. Electroacupuncture inhibited proteins, activation microglia release factors area. Therefore, this shows relieve regulating microglial factor through pathway.

Language: Английский

Microglial STING activation alleviates nerve injury-induced neuropathic pain in male but not female mice DOI Creative Commons
Arthur Silveira Prudente, Sang Hoon Lee,

Jueun Roh

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 51 - 65

Published: Jan. 6, 2024

Microglia, resident immune cells in the central nervous system, play a role neuroinflammation and development of neuropathic pain. We found that stimulator interferon genes (STING) is predominantly expressed spinal microglia upregulated after peripheral nerve injury. However, mechanical allodynia, as marker pain following injury, did not require microglial STING expression. In contrast, activation by specific agonists (ADU-S100, 35 nmol) significantly alleviated male mice, but female mice. mice leads to increase proinflammatory cytokines may counteract analgesic effect ADU-S100. Microglial expression type I interferon-ß (IFN-ß) signaling were required for effects Mechanistically, downstream TANK-binding kinase 1 (TBK1) production IFN-ß, partly account observed. These findings suggest could be potential therapeutic intervention pain, particularly males.

Language: Английский

Citations

11
Edaravone dexborneol ameliorates cognitive impairment by regulating the NF-κB pathway through AHR and promoting microglial polarization towards the M2 phenotype in mice with bilateral carotid artery stenosis (BCAS) DOI
Lei Li, Guojun He,

Mingyu Shi

et al.

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 957, P. 176036 - 176036

Published: Sept. 4, 2023

Language: Английский

Citations

19
Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction DOI Creative Commons
Úrzula Franco‐Enzástiga, Keerthana Natarajan, Eric T. David

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(2), P. 108808 - 108808

Published: Jan. 8, 2024

Type I interferons (IFNs) increase the excitability of dorsal root ganglia (DRGs) neurons via MNK-eIF4E signaling to promote pain sensitization in mice. Activation stimulator interferon response cGAMP interactor 1 (STING) is pivotal for type IFN induction. We hypothesized that vinorelbine, a chemotherapeutic and activator STING, would cause neuropathic pain-like state mice STING DRG associated with production. Vinorelbine caused tactile allodynia grimacing wild-type (WT) increased p-IRF3, IFNs, p-eIF4E peripheral nerves. Supporting our hypothesis, vinorelbine failed induce IRF3-IFNs-MNK-eIF4E StingGt/Gt and, subsequently, pain. The vinorelbine-elicited was not observed Mknk1−/− (MNK1 knockout) nerves consistent attenuated pro-nociceptive effect these Our findings show activation periphery causes through nociceptors.

Language: Английский

Citations

7
STING signaling in the brain: Molecular threats, signaling activities, and therapeutic challenges DOI Creative Commons
Kun Yang, Zhen Tang, Cong Xing

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(4), P. 539 - 557

Published: Nov. 8, 2023

Language: Английский

Citations

17
The bidirectional roles of the cGAS-STING pathway in pain processing: Cellular and molecular mechanisms DOI Open Access

Yingjie Hu,

Yuye Chen, Tongtong Liu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114869 - 114869

Published: May 12, 2023

Pain is a common clinical condition. However, the mechanisms underlying pain are not yet fully understood. It known that neuroimmune system plays critical role in pathogenesis of pain. Recent studies indicated cyclic-GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway can activate innate immune by sensing both extrinsic and intrinsic double-stranded DNA cytoplasm, which involved processing. In this review, we summarise (1) roles cGAS-STING different models, (2) effect cells during regulation, (3) downstream molecular regulation. This review provides evidence has pro- anti-nociceptive effects models. functions neuron, microglia, macrophage, T cells. Its molecules include IFN-I, NF-κB, NLRP3, eIF2α. The bidirectional processing mediated regulating nociceptive neuronal sensitivity neuroinflammatory responses. their special brain regions, activation astrocytes, phases require further exploration.

Language: Английский

Citations

16
Understanding the initiation, delivery and processing of bone cancer pain from the peripheral to the central nervous system DOI
Lei Yang, Beibei Liu,

Zheng Shang

et al.

Neuropharmacology, Journal Year: 2023, Volume and Issue: 237, P. 109641 - 109641

Published: June 30, 2023

Language: Английский

Citations

12
The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases DOI Creative Commons
Yuxin Zhang, Meijuan Zou, Hao Wu

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 202, P. 106710 - 106710

Published: Oct. 28, 2024

Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by damage to specific cell populations in the nervous system, ultimately leading disability or death. Effective treatments for these still lacking, due limited understanding their pathogeneses, which involve multiple cellular and molecular pathways. The triggering an immune response is feature neurodegenerative disorders. A critical challenge intricate interplay between neuroinflammation, neurodegeneration, responses, not yet fully characterized. In recent years, cyclic GMP-AMP synthase (cGAS)-stimulator interferon gene (STING) pathway, crucial intracellular DNA sensing, has gradually gained attention. However, roles this pathway within types such as cells, glial neuronal its contribution ND pathogenesis, remain elucidated. review, we systematically explore how cGAS-STING signaling links various with related effector pathways under context NDs multifaceted therapeutic directions. We emphasize discovery condition-dependent heterogeneity integral diverse responses potential targets. Additionally, review pathogenic role activation Parkinson's disease, ataxia-telangiectasia, amyotrophic lateral sclerosis. focus on complex bidirectional Alzheimer's Huntington's sclerosis, revealing double-edged nature disease progression. objective elucidate pivotal pathogenesis catalyze new insights facilitating development novel strategies.

Language: Английский

Citations

4
Mechanisms of Cancer-Induced Bone Pain DOI Creative Commons
Xuejuan Wang, Li Li, Yun Wang

et al.

Journal of Pain Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 315 - 326

Published: Jan. 1, 2025

Bone is a common site of advanced cancer metastasis, second only to the lungs and liver.Cancer-induced bone pain (CIBP) persistent intense that caused by combination inflammatory neuropathic factors.As CIBP progresses, degree intensifies.Despite advancements in medical technology, treatment outcomes patients with remain unsatisfactory, severe can typically be controlled opioid medications.However, treated medications often develop tolerance.Therefore, they may require dose increases, which increase severity opioid-induced side effects, turn influencing quality life.The peripheral mechanisms primarily involve tissue damage, tumor microenvironment formation, changes dorsal root ganglion.The central usually biochemical electrophysiological spinal cord brain.The main processing center for nociceptive signals.When cells produce mediators acidify or damage nerve endings, becomes excessively stimulated, resulting increased prolonged signals propagate higher nervous system through ascending pathway.There are substantial differences generation between pain.Therefore, understanding underpinning development at level crucial optimizing management.This study explores pathogenesis describes recently proposed methods CIBP.

Language: Английский

Citations

0
Unraveling the PVTGlu-mPFCGlu Circuit: A New Frontier in Chronic Pain Management for Bone Cancer Pain DOI Creative Commons
Liqun Duan, Qianliang Wang, Jianpeng Chen

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 222, P. 111235 - 111235

Published: Feb. 6, 2025

Bone cancer pain (BCP) is a type of ongoing or breakthrough caused by primary bone tumor metastasis. BCP impairs patients' quality life. Depending upon clinical observations, the administration centrally acting analgesic has been associated with alleviation symptoms patients. Central nervous system sensitization performs crucial role in pain-regulating perception BCP. Nevertheless, precise neural circuitry and mechanism action remain enigmatic. In present study, we observed activation glutamatergic neurons Prelimbic cortex (mPFC) paraventricular thalamus (PVT) mice. Experimental validation using viral tracers confirmed existence projection pathway between PVT mPFC. Inhibition input from to mPFC alleviates chronic BCP, whereas PVTGlu-mPFCGlu induces These findings imply pivotal for circuit regulation

Language: Английский

Citations

0
Decoding STING’s roles in cancer: immunity, pain, dormancy, and autophagy DOI
Huan‐Xin Lin, Ya‐ling Tang,

Xinhua Liang

et al.

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

Citations

0