Bone mesenchymal stem cells attenuate resiniferatoxin-induced neuralgia via inhibiting TRPA1-PKCδ-P38/MAPK-p-P65 pathway in mice

Li, Nan-Qi; Peng, Zhe; Xu, Wenwen; An, Kai Nan; Wan, Li

doi:10.1016/j.brainresbull.2021.06.004

Cited by 13 publications

(13 citation statements)

References 35 publications

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“…MSCs can preserve regenerative function after cryopreservation, improving synaptic transmission and repairing neuronal networks 13,14 . In recent years, numerous reports have shown that MSCs attenuated hypersensitivity induced by neuropathic pain 15–18 . In addition to neuropathic pain that is commonly resulted from a lesion in the central or peripheral branches of nerves, inflammatory pain is characterized by high levels of inflammatory components, which are increased by activation of the immune system and/or by tissue injury or infection 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Bone marrow‐derived mesenchymal stem cells attenuate complete Freund's adjuvant‐induced inflammatory pain by inhibiting the expression of P2X3

et al. 2023

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Bone marrow‐derived mesenchymal stem cells (BMSCs) show a good property for pain treatment by modulating inflammatory response. However, the underlying therapeutic effect and related mechanism of BMSCs on inflammatory pain remain unclear. Therefore, we explored the function and potential mechanism of BMSCs performing in a complete Freund's adjuvant (CFA)‐induced inflammatory pain model in this study. Here, BMSCs were injected into the CFA‐treated rats, and we used behavioural tests to evaluate the changes in hypersensitivity. High‐throughput sequencing was used to screen out the hub genes. Molecular biology experiments were performed to detect the level of P2X3 or inflammatory mediators in rats and observed the distribution of P2X3 in neural cells. Furthermore, the function of the P2X3 was explored via inhibitor and activator experiments. Finally, we found that BMSCs alleviated hyperalgesia and spinal levels of pro‐inflammatory factors in CFA‐treated rats. High‐throughput sequencing showed that P2X3 and P2X7 were identified as hub genes, and only the expression level of P2X3 was significantly down‐regulated after BMSCs treatment. Immunohistochemistry showed that P2X3 mainly colocalized with microglia and astrocytes. The levels of P2X3 and pro‐inflammatory factors were all significantly reduced after BMSC injection. Moreover, similar attenuation was found in the CFA‐treated rats after injecting the P2X3 inhibitor, and a P2X3 antagonist reversed the attenuation induced by the BMSCs. These findings suggest that BMSCs exerted a therapeutic effect on inflammatory pain by inhibiting the expression of P2X3 and the excessive production of inflammatory mediators was associated with an increased P2X3 level and BMSC therapy reverse these effects.

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Section: Introductionmentioning

confidence: 99%

Bone marrow‐derived mesenchymal stem cells attenuate complete Freund's adjuvant‐induced inflammatory pain by inhibiting the expression of P2X3

et al. 2023

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“…On the other hand, inhibition of P2X7R of SGCs could decrease the concentration of intracellular Ca 2+ and inhibit the activity of PKC-ε in neurons. Studies have shown that blocking p38 MAPK does not affect PKC-phosphorylation, whereas blocking PKC-abolishes phosphorylation of p38 MAPK [31,63]. Therefore, p38 MAPK was identi ed as a downstream target of PKC-.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of P2X7 receptor downregulates neuronal TRPV1 expression in rat dorsal root ganglion

Wang

Chen

Xing

et al. 2022

Preprint

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The purinergic 2X7 receptor (P2X7R) is an ATP-gated ion channel that can conduct extracellular signals and induce corresponding biological effects. Transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel that maintains normal physiological functions. Numerous studies have shown that P2X7R and TRPV1 are strongly associated with inflammatory reactions, so we aimed to investigate the effect of knockdown of P2X7R in rat satellite glial cells (SGCs) on neuronal TRPV1 expression under a high glucose and high free-fat (HGHF) environment. We found that treatment with P2X7 short hairpin RNA (shRNA) reduced the expressions of the P2X7R protein and mRNA of SCGs in the dorsal root ganglion, downregulated the release of tumor necrosis factor-alpha and interleukin-1 beta via the Ca2+/p38 MAPK/NF-kB pathway. After coculture of neurons with SGCs, TRPV1 expression in neurons was reduced via Ca2+/PKC-ɛ/p38 MAPK pathway. These results suggest that reducing P2X7R on SCGs in an HGHF environment results in decreasing neuronal TRPV1 expression via the Ca2+/PKC-ɛ/p38 MAPK pathway.

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“…One noteworthy outcome of MAPK pathway activation in the context of TBIs is its impact on osteoblast activity. [74,75] Osteoblasts undergo a resurgence with regard to their functional capacity when stimulated by the MAPK signaling pathways. [75] This manifests as an upregulation in essential osteoblastic processes, including increased proliferation and differentiation.…”

Section: Mapk Signaling Pathwaymentioning

confidence: 99%

“…In response to TBIs, several MAPK signaling pathways are activated, including the extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase, and p38 MAPK pathways [74] . The activation of these pathways stimulates a cascade of intracellular events that culminate in cellular responses associated with bone healing.…”

Section: Signaling Pathways In Tbi‐induced Bone Healingmentioning

confidence: 99%

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The mechanism of bone healing after traumatic brain injury

Xiong,

Zhong,

2023

Brain-X

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A growing body of evidence suggests that patients who experience traumatic brain injuries (TBIs) exhibit significantly shorter healing periods compared to those with isolated fractures. However, the precise underlying mechanism behind this phenomenon remains unclear. Recent studies have shed light on the potential role of hormonal signals and neural circuits originating in the hypothalamus, which play vital roles in regulating the skeletal system. Despite these advances, there is a lack of comprehensive research summarizing the crucial role of bone healing in TBIs and the underlying mechanisms. This review aimed to explore the underlying mechanisms responsible for the accelerated bone healing observed in TBI patients, with a specific focus on the intricate crosstalk between TBI and bone remodeling. Additionally, we comprehensively discuss and summarize the beneficial effects of TBI on the skeletal system and examine the TBI‐induced signaling pathways that result in accelerated fracture healing and bone remodeling. By dissecting these pathways, we aim to identify potential targets for intervention and bone repair promotion.

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Bone mesenchymal stem cells attenuate resiniferatoxin-induced neuralgia via inhibiting TRPA1-PKCδ-P38/MAPK-p-P65 pathway in mice

Cited by 13 publications

References 35 publications

Bone marrow‐derived mesenchymal stem cells attenuate complete Freund's adjuvant‐induced inflammatory pain by inhibiting the expression of P2X3

Bone marrow‐derived mesenchymal stem cells attenuate complete Freund's adjuvant‐induced inflammatory pain by inhibiting the expression of P2X3

Inhibition of P2X7 receptor downregulates neuronal TRPV1 expression in rat dorsal root ganglion

The mechanism of bone healing after traumatic brain injury

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