Microglia-derived TNF-α inhibiting GABAergic neurons in the anterior lateral bed nucleus of the stria terminalis precipitates visceral hypersensitivity induced by colorectal distension in rats

Ji, Ningfei; Meng, Qingxiang; Wang, Ying; Zhou, Ziming; Song, Yu; Hua, Rong; Zhang, Yongmei

doi:10.1016/j.ynstr.2022.100449

Cited by 8 publications

(8 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some animal studies have successfully targeted microglia using the eliminator PLX5622 and the inhibitor minocycline to inhibit central inflammatory responses to treat CNS diseases, including chronic pain ( 14 - 16 ). For example, our previous study found that the injection of the microglia inhibitor minocycline into the PVN alleviated irritable bowel syndrome (IBS)-like visceral pain ( 8 ). Similarly, in this study, we found that PCVP was alleviated by the microinjection of minocycline to inhibit PVN microglia, which provides further evidence that microglia are effective targets for chronic pain treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Neuroinflammation in the central nervous system (CNS) primarily manifests through the activation of various glial cells, particularly microglia and astrocytes, which facilitate the release of inflammatory mediators leading to chronic pain ( 8 - 10 ). The close proximity between glia (astrocytes and microglia) neurons facilitates glial activation via neurotransmission, as glia express a diverse array of functional neurotransmitter receptors ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, this cascade further contributes to the initiation and maintenance of chronic pain ( 12 , 13 ). The eliminator PLX5622 (C 21 H 19 F 2 N 5 O) and the inhibitor minocycline have been successfully used to target microglia to inhibit central sensitization to relieve chronic pain in animals ( 8 , 14 - 16 ). Additionally, studies have also explored emerging chemogenetic methods to inhibit astrocytes and thus regulate central inflammation ( 17 - 19 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neuroinflammation in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

Ji,

Li,

Cao

et al. 2024

J Gastrointest Oncol

View full text Add to dashboard Cite

Background Given the pivotal role of neuroinflammation in chronic pain and that the paraventricular nucleus of the hypothalamus (PVN) is a crucial brain region involved in visceral pain regulation, we sought to investigate whether the targeted modulation of microglia and astrocytes in the PVN could ameliorate pancreatic cancer-induced visceral pain (PCVP) in mice. Methods Using a mouse model of PCVP, achieved by tumor cell injection at the head of the pancreas, we measure the number of glial cells, and at the same time we employed minocycline to inhibit microglia and chemogenetic methods to suppress astrocytes in order to investigate the respective roles of microglia and astrocytes within the PVN in PCVP. Results Mice exhibited visceral pain at 12, 15 and 18 days post-tumor cell injection. We observed a significant increase in the population of both microglia and astrocytes. Inhibition of microglial activity through minocycline microinjection into the PVN resulted in alleviation of visceral pain within 30 and 60 min. Similarly, chemogenetic inhibition of astrocyte function at 14 and 21 days post-injection also led to relief from visceral pain. Conclusions This study found that PVN microglia and astrocytes were involved in regulating PCVP. Our results suggest that targeting glia may be a potential approach for alleviating visceral pain in patients with pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroinflammation in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

Ji,

Li,

Cao

et al. 2024

J Gastrointest Oncol

View full text Add to dashboard Cite

show abstract

“…Moreover, in the stress-induced irritable bowel syndrome rat model, minocycline infusion reversed stress-induced microgliosis via inhibiting the p38-MAPK pathway, abolishing visceral hypersensitivity as in stress-naive rats (Yuan et al 2020 ). In the colorectal distension rat model of irritable bowel syndrome, minocycline curbed the activated microglia-dependent suppression of GABAergic neuronal activity which increased the visceral pain threshold (Ji et al 2022 ). In context, cannabidiol has been demonstrated to attenuate pain sensation through its microglia modulatory effects.…”

Section: Targeting Microglia As a New Therapeutic Strategy In Treatin...mentioning

confidence: 99%

Microglia polarization in nociplastic pain: mechanisms and perspectives

et al. 2023

View full text Add to dashboard Cite

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.

show abstract

“…Although there is a lack of evidence for microglial activation in population cohort studies, various animal models of visceral hypersensitivity in IBS support this hypothesis. In animal models of IBS visceral hypersensitivity, the number of microglial cells in the dorsal horn of the spinal cord and brain increases, and is substantially activated ( Zhang et al, 2016 ; Lucarini et al, 2020 ; Yuan et al, 2020 ; Atmani et al, 2022 ; Ji et al, 2022 ). The number of microglia in the dorsal horn of the L6-S1 spinal cord increased in a mouse model of visceral hypersensitivity, induced by intravesical perfusion of acetic acid ( Atmani et al, 2022 ).…”

Section: Microglia Play An Important Role In Gut–brain Interactionsmentioning

confidence: 99%

“Sentinel or accomplice”: gut microbiota and microglia crosstalk in disorders of gut–brain interaction

Zheng

Zhang

et al. 2023

Protein &Amp; Cell

View full text Add to dashboard Cite

Abnormal brain-gut interaction is considered the core pathological mechanism behind the disorders of gut-brain interaction, in which the intestinal microbiota plays an important role. Microglia are the “sentinels” of the central nervous system, which participate in tissue damage caused by traumatic brain injury, resist central infection and participate in neurogenesis, and are involved in the occurrence of various neurological diseases. With in-depth research on disorders of gut-brain interaction, we could find an interaction between the intestinal microbiota and microglia and that they are jointly involved in the occurrence of disorders of gut-brain interaction, especially in individuals with comorbidities of mental disorders, such as irritable bowel syndrome. This bidirectional regulation of microbiota and microglia provides a new direction for the treatment of disorders of gut-brain interaction. In this review, we focus on the role and underlying mechanism of the interaction between gut microbiota and microglia in disorders of gut-brain interaction, especially irritable bowel syndrome, and the corresponding clinical application prospects and highlight its potential to treat disorders of gut-brain interaction in individuals with psychiatric comorbidities.

show abstract

Microglia-derived TNF-α inhibiting GABAergic neurons in the anterior lateral bed nucleus of the stria terminalis precipitates visceral hypersensitivity induced by colorectal distension in rats

Cited by 8 publications

References 54 publications

Neuroinflammation in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

Neuroinflammation in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

Microglia polarization in nociplastic pain: mechanisms and perspectives

“Sentinel or accomplice”: gut microbiota and microglia crosstalk in disorders of gut–brain interaction

Contact Info

Product

Resources

About