Effect of artemisinin on neuropathic pain mediated by P2X4 receptor in dorsal root ganglia

Ying, Mofeng; Liu, Hui; Zhang, Tengling; Jiang, Chenxu; Gong, Yingxin; Wu, Bing; Zou, Lifang; Yi, Zhihua; Rao, Shenqiang; Li, Guilin; Zhang, Chunping; Jia, Tianyu; Zhao, Shanhong; Yuan, Huilong; Shi, Liran; Li, Lin; Liang, Shangdong; Liu, Shuangmei

doi:10.1016/j.neuint.2017.02.004

Cited by 46 publications

(41 citation statements)

References 29 publications

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“…In the CNS, P2X4 receptor plays a role in modulating synaptic transmission and communication between neurons and neighboring glial cells . Our previous study confirmed that P2X4 receptor expressed in the satellite glial cells (SGCs) of dorsal root ganglia and involved in the neuropathic pain …”

Section: Introductionsupporting

confidence: 67%

Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia

Zhu

Chen

Dai

et al. 2018

Environmental Toxicology

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Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG). Rats were given lead acetate through drinking water freely at doses of 0 g/L (control group), 0.5 g/L (low lead group), and 2 g/L (high lead group) for 1 year. Our results demonstrated that lead exposure caused autonomic nervous dysfunction, including blood pressure and heart rate increased and heart rate variability (HRV) decreased. Western blotting results indicated that after lead exposure, the protein expression levels in the SG of P2X4 receptor, IL-1β and Cx43 were up-regulated, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was activated. Real-time PCR results showed that the mRNA expression of P2X4 receptor in the SG was higher in lead exposure group than that in the control group. Double-labeled immunofluorescence results showed that P2X4 receptor was co-expressed with glutamine synthetase (GS), the marker of satellite glial cells (SGCs). These changes were positively correlated with the dose of lead exposure. The up-regulated expression of P2X4 receptor in SGCs of the SG maybe enhance the sympathoexcitatory response induced by chronic lead exposure.

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Section: Introductionsupporting

confidence: 67%

Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia

Zhu

Chen

Dai

et al. 2018

Environmental Toxicology

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“…It was demonstrated that artemisinin attenuates portal hypertension in rodents with hepatic fibrosis by inhibiting the activation and contraction of hepatic stellate cells via farnesoid X receptor (FXR) ( Xu W. et al, 2017 ). Artemisinin was also proven to inhibit nociceptive transmission by downregulating the P2X4 receptors and glial fibrillary acidic proteins in satellite glial cells of the dorsal root ganglia, thus relieving neuropathic pain in the chronic constriction injury rat model ( Ying et al, 2017 ).…”

Section: Artemisinin Targets Receptors Impacting On Signaling Cascadementioning

confidence: 99%

Artemisinin: A Panacea Eligible for Unrestrictive Use?

et al. 2017

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Although artemisinin has been used as anti-malarial drug, accumulating evidence on the extended therapeutic potential of artemisinin emerges. Apart from anti-malaria and anti-tumor, artemisinin can also exert beneficial effects on some metabolic disorders, such as obesity, diabetes, and aging-related diseases. However, whether artemisinin should be applied to treatment of the wide-spectrum diseases is debating. Here, we discuss the predisposition of a raised risk of malarial resistance to artemisinin from consideration of the multi-target and non-specific features of artemisinin.

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“…Damage causes SGCs to contribute to neuropathic pain [12,13,15,30]. GFAP was elevated in DRG SGCs after gp120+ddC treatment since GFAP is considered a marker of SGCs activation, the finding suggested the activation of SGCs Fig.…”

Section: Discussionmentioning

confidence: 93%

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine

Xie

Zhou

et al. 2017

Purinergic Signalling

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The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y 12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y 12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2′,3′-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIVgp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y 12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca 2+ ] i activated by the P2Y 12 receptor agonist 2-(Methylthio) adenosine 5′-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y 12 receptor shRNA treatment inhibited 2-MeSADPinduced [Ca 2+ ] i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y 12 receptor in DRG SGCs reduced the release of proinflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y 12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

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Effect of artemisinin on neuropathic pain mediated by P2X4 receptor in dorsal root ganglia

Cited by 46 publications

References 29 publications

Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia

Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia

Artemisinin: A Panacea Eligible for Unrestrictive Use?

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine

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