VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X2/3 receptor of primary sensory neurons

Lin, Jiari; Li, Guilin; Den, Xiaorong; Xu, Changshui; Liu, Shuangmei; Gao, Yun; Han, Lei; Zhang, Jun; Li, Xin; Liang, Shangdong

doi:10.1016/j.brainresbull.2010.08.002

Cited by 87 publications

(75 citation statements)

References 46 publications

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“…Consistent with this idea, VEGF-A administration increases phrenic nerve output in adult rats to regulate spinal respiratory functions (Dale-Nagle et al, 2011). In vivo, blocking VEGF-A activity by antibody administration also increases pain thresholds after chronic nerve constriction injury in rats (Lin et al, 2010).…”

Section: Reviewmentioning

confidence: 73%

Diverse roles for VEGF-A in the nervous system

2012

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Vascular endothelial growth factor A (VEGF-A) is best known for its essential roles in blood vessel growth. However, evidence has emerged that VEGF-A also promotes a wide range of neuronal functions, both in vitro and in vivo, including neurogenesis, neuronal migration, neuronal survival and axon guidance. Recent studies have employed mouse models to distinguish the direct effects of VEGF on neurons from its indirect, vessel-mediated effects. Ultimately, refining our knowledge of VEGF signalling pathways in neurons should help us to understand how the current use of therapeutics targeting the VEGF pathway in cancer and eye disease might be expanded to promote neuronal health and nerve repair.

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Section: Reviewmentioning

confidence: 73%

Diverse roles for VEGF-A in the nervous system

2012

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“…The P2X3 receptor is most highly expressed in a subpopulation of small diameter primary afferent neurons. The expression of P2X3 protein and messenger RNA (mRNA) is increased following chronic constriction injury (CCI) of the sciatic nerve [11][12][13][14][15][16][17][18]. The P2X3 receptor plays a crucial role in chronic neuropathic pain [11][12][13][15][16][17][18][19], and this receptor has been shown to mediate mechanical allodynia in diabetic neuropathic rats [20].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia

Xuan

Zhao

et al. 2017

Purinergic Signalling

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Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). More than 90% of all cases of DM belong to type 2 diabetes mellitus (T2DM). Emodin is the main active component of Radix et rhizoma rhei and has anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. Nanoparticle encapsulation of drugs is beneficial for drug targeting and bioavailability as well as for lowering drug toxicity side effects. The aim of this study was to investigate the effects of nanoparticleencapsulated emodin (nano emodin) on diabetic neuropathic pain (DNP) mediated by the Purin 2X3 (P2X3) receptor in the dorsal root ganglia (DRG). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with nano emodin were higher compared with those in T2DM rats. Expression levels of P2X3 protein and messenger RNA (mRNA) in the DRG of T2DM rats were higher than those of controls, while levels in T2DM rats treated with nano emodin were significantly lower than those of the T2DM rats. Phosphorylation and activation of ERK1/2 in the T2DM DRG were decreased by nano emodin treatment. Nano emodin significantly inhibited currents activated by the P2X3 agonist α,β-meATP in HEK293 cells transfected with the P2X3 receptor. Therefore, nano emodin treatment may relieve DNP by decreasing excitatory transmission mediated by the DRG P2X3 receptor in T2DM rats.

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“…It is released upon cell stress, stimulation, or damage, thus activating P2XRs present in sensory afferent endings to produce pain (15). Purinergic P2X ligand-gated ion channel 3 receptors (P2X3Rs) and P2X2Rs/P2X3Rs are preferentially expressed in DRG neurons and are upregulated under neuropathic (16)(17)(18), inflammatory (19), and visceral pain hypersensitivity conditions (20). However, the underlying mechanism by which p2xr gene expression is upregulated remains unknown under diabetic conditions.…”

mentioning

confidence: 99%

Promoted Interaction of Nuclear Factor-κB With Demethylated Purinergic P2X3 Receptor Gene Contributes to Neuropathic Pain in Rats With Diabetes

Zhang

Zhou

et al. 2015

Diabetes

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Painful diabetic neuropathy is a common complication of diabetes produced by mechanisms that as yet are incompletely defined. The aim of this study was to investigate the roles of nuclear factor-kB (NF-kB) in the regulation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3R) plasticity in dorsal root ganglion (DRG) neurons of rats with painful diabetes. Here, we showed that hindpaw pain hypersensitivity in streptozocininduced diabetic rats was attenuated by treatment with purinergic receptor antagonist suramin or A-317491. The expression and function of P2X3Rs was markedly enhanced in hindpaw-innervated DRG neurons in diabetic rats. The CpG (cytosine guanine dinucleotide) island in the p2x3r gene promoter region was significantly demethylated, and the expression of DNA methyltransferase 3b was remarkably downregulated in DRGs in diabetic rats. The binding ability of p65 (an active form of NF-kB) with the p2x3r gene promoter region and p65 expression were enhanced significantly in diabetes. The inhibition of p65 signaling using the NF-kB inhibitor pyrrolidine dithiocarbamate or recombinant lentiviral vectors designated as lentiviral vector-p65 small interfering RNA remarkably suppressed P2X3R activities and attenuated diabetic pain hypersensitivity. Insulin treatment significantly attenuated pain hypersensitivity and suppressed the expression of p65 and P2X3Rs. Our findings suggest that the p2x3r gene promoter DNA demethylation and enhanced interaction with p65 contributes to P2X3R sensitization and diabetic pain hypersensitivity.

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VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X2/3 receptor of primary sensory neurons

Cited by 87 publications

References 46 publications

Diverse roles for VEGF-A in the nervous system

Diverse roles for VEGF-A in the nervous system

Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia

Promoted Interaction of Nuclear Factor-κB With Demethylated Purinergic P2X3 Receptor Gene Contributes to Neuropathic Pain in Rats With Diabetes

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