Paeonol alleviates neuropathic pain by modulating microglial <scp>M1</scp> and <scp>M2</scp> polarization via the <scp>RhoA</scp>/<scp>p38MAPK</scp> signaling pathway

Li, Xin; Shi, Huimei; Zhang, Di; Jing, Bei; Chen, Zhenni; Zheng, Yipeng; Chang, Shiquan; Gao, Li; Zhao, Guoping

doi:10.1111/cns.14211

Cited by 12 publications

(3 citation statements)

References 39 publications

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“…An NP model of chronic compression injury (CCI) of the sciatic nerve in rats was established according to our previous study (Li et al, 2023). First, we injected the rats with sodium pentobarbital (2%; 50 mg/kg), after which the rats were fixed, and the right sciatic nerve was exposed.…”

Section: Np Modelmentioning

confidence: 99%

Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate neuropathic pain

Si,

Li,

Jing

et al. 2023

Phytotherapy Research

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Abstract(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme‐linked immunosorbent assay, hematoxylin‐esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT‐PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL‐1β and IL‐8 levels and increased serum IL‐4 and TGF‐β levels in CCI rats. Stigmasterol reduced IL‐1β, COX‐2, and TLR4 expression in the right sciatic nerve and IL‐1β expression in the spinal cord. Stigmasterol reduced the expression of Iba‐1, TLR4, MyD88, pNF‐κB, pP38 MAPK, pJNK, pERK, COX‐2, IL‐1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL‐10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)‐induced microglia and decreased the expression of Iba‐1, TLR4, MyD88, pNF‐κB, pP38 MAPK, pJNK, pERK, iNOS, COX‐2, and IL‐1β in LPS‐treated microglia while increasing the expression of Arg‐1 and IL‐10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate NP.

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Section: Np Modelmentioning

confidence: 99%

Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate neuropathic pain

Si,

Li,

Jing

et al. 2023

Phytotherapy Research

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“…Microglia are resident macrophage‐like immune cells in the CNS and are thought to be crucial in nerve pain. 72 Among the three types of glial cells in the CNS, although oligodendrocytes and astrocytes are closely related to neurons, microglia have received more attention due to the fact that nerve injury‐induced changes in microglia are more intense than in oligodendrocytes and astrocytes. Nerve injury induces massive proliferation of spinal cord microglia, 73 which release proinflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) and a range of chemokines (including, but not limited to, monocyte chemotactic protein‐1 (MCP‐1), CCL20, CCL5, CXCL1, CXCL9, and CXCL10).…”

Section: Roles Of Mapk In the Treatment Of Scimentioning

confidence: 99%

Advances of the MAPK pathway in the treatment of spinal cord injury

Huang,

Zhang,

Shu

et al. 2024

CNS Neurosci Ther

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Spinal cord injury (SCI) represents a complex pathology within the central nervous system (CNS), leading to severe sensory and motor impairments. It activates various signaling pathways, notably the mitogen‐activated protein kinase (MAPK) pathway. Present treatment approaches primarily focus on symptomatic relief, lacking efficacy in addressing the underlying pathophysiological mechanisms. Emerging research underscores the significance of the MAPK pathway in neuronal differentiation, growth, survival, axonal regeneration, and inflammatory responses post‐SCI. Modulating this pathway post‐injury has shown promise in attenuating inflammation, minimizing apoptosis, alleviating neuropathic pain, and fostering neural regeneration. Given its pivotal role, the MAPK pathway emerges as a potential therapeutic target in SCI management. This review synthesizes current knowledge on SCI pathology, delineates the MAPK pathway's characteristics, and explores its dual roles in SCI pathology and therapeutic interventions. Furthermore, it addresses the existing challenges in MAPK research in the context of SCI, proposing solutions to overcome these hurdles. Our aim is to offer a comprehensive reference for future research on the MAPK pathway and SCI, laying the groundwork for targeted therapeutic strategies.

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“…The evidence mentioned above indicates a strong connection between microglia and neuroinflammation. Consequently, modulating the polarization phenotype of microglia serves as a means to impede the inflammatory response, thus exerting a protective influence on the nervous system [ 36 , 37 , 38 ]. Overall, microglia serve as a double-edged sword in neuroinflammation after neuropathic pain.…”

Section: Neuroinflammationmentioning

confidence: 99%

New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation

Luo,

Huang

2024

IJMS

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Neuropathic pain, which refers to pain caused by a lesion or disease of the somatosensory system, represents a wide variety of peripheral or central disorders. Treating neuropathic pain is quite demanding, primarily because of its intricate underlying etiological mechanisms. The central nervous system relies on microglia to maintain balance, as they are associated with serving primary immune responses in the brain next to cell communication. Ferroptosis, driven by phospholipid peroxidation and regulated by iron, is a vital mechanism of cell death regulation. Neuroinflammation can be triggered by ferroptosis in microglia, which contributes to the release of inflammatory cytokines. Conversely, neuroinflammation can induce iron accumulation in microglia, resulting in microglial ferroptosis. Accumulating evidence suggests that neuroinflammation, characterized by glial cell activation and the release of inflammatory substances, significantly exacerbates the development of neuropathic pain. By inhibiting microglial ferroptosis, it may be possible to prevent neuroinflammation and subsequently alleviate neuropathic pain. The activation of the homopentameric α7 subtype of the neuronal nicotinic acetylcholine receptor (α7nAChR) has the potential to suppress microglial activation, transitioning M1 microglia to an M2 phenotype, facilitating the release of anti-inflammatory factors, and ultimately reducing neuropathic pain. Recent years have witnessed a growing recognition of the regulatory role of α7nAChR in ferroptosis, which could be a potential target for treating neuropathic pain. This review summarizes the mechanisms related to α7nAChR and the progress of ferroptosis in neuropathic pain according to recent research. Such an exploration will help to elucidate the relationship between α7nAChR, ferroptosis, and neuroinflammation and provide new insights into neuropathic pain management.

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Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA/p38MAPK signaling pathway

Cited by 12 publications

References 39 publications

Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate neuropathic pain

Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate neuropathic pain

Advances of the MAPK pathway in the treatment of spinal cord injury

New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation

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