Involvement of Wnt/β-catenin signaling in the development of neuropathic pain

Itokazu, Takahide; Hayano, Yasufumi; Takahashi, Ryōsuke; Yamashita, Toshio

doi:10.1016/j.neures.2013.12.002

Cited by 53 publications

(52 citation statements)

References 38 publications

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“…Previous studies highlight the vital role of spinal β-catenin in neuropathic pain 16 24 25. Neuropathic pain upregulates spinal β-catenin, and the blockade of Wnt/β-catenin signals attenuates the induction of neuropathic pain 24. In the present study, we have demonstrated that both PRF-DRG and PRF-SN could downregulate the expression of β-catenin, indicating the involvement of β-catenin signal pathway in PRF’s analgesic action.…”

Section: Discussionsupporting

confidence: 59%

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal β-catenin in chronic constriction injury rats

Jiang

et al. 2019

Reg Anesth Pain Med

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Background and objectivesPulsed radiofrequency (PRF) is a minimal neurodestructive interventional pain therapy. However, its analgesic mechanism remains largely unclear. We aimed to investigate the peripheral and spinal mechanisms of PRF applied either adjacent to the ipsilateral L5 dorsal root ganglion (PRF-DRG) or PRF to the sciatic nerve (PRF-SN) in the neuropathic pain behavior induced by chronic constriction injury (CCI) in rats.MethodsOn day 0, CCI or sham surgeries were performed. Rats then received either PRF-DRG, PRF-SN, or sham PRF treatment on day 4. Pain behavioral tests were conducted before surgeries and on days 1, 3, 5, 7, 9, 11, 13, and 14. After the behavioral tests, the rats were sacrificed. The venous blood or sciatic nerve samples were collected for ELISAs and the dorsal horns of the L4–L6 spinal cord were collected for western blot examination.ResultsThe mechanical allodynia and the thermal hyperalgesia has been relieved by a single PRF-DRG or PRF-SN application. In addition, the analgesic effect of PRF-DRG was superior to PRF-SN on CCI-induced neuropathic pain. Either PRF-DRG or PRF-SN reversed the enhancement of interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels in the blood of CCI rats. PRF-DRG or PRF-SN also downregulated spinal β-catenin expression.ConclusionsPRF treatment either to DRG or to sciatic nerve reduced neuropathic pain behavior, and reduced peripheral levels of pro-inflammatory cytokines and spinal β-catenin expression in CCI rats. PRF to DRG has a better analgesic effect than PRF to the nerve.

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Section: Discussionsupporting

confidence: 59%

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal β-catenin in chronic constriction injury rats

Jiang

et al. 2019

Reg Anesth Pain Med

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“…6). Wnt signaling has been shown to influence spinal cord dorsal horn and dorsal root ganglia patterning during the pathogenesis and the development of neuropathic pain (Itokazu et al 2014;Zhang et al 2013). Based on these, we speculate that TCF4 may be involved in the maintenance of neuropathic pain through mediating the activation of Wnt/β-catenin pathway following peripheral nerve injury in rats.…”

Section: Activation Of Wnt/β-catenin Signaling In the Dorsal Root Ganmentioning

confidence: 77%

“…Previous studies have shown that Wnt/β-catenin signaling was activated in the spinal cord in the partial sciatic nerve ligation (PSL) model (Itokazu et al 2014). Nevertheless, it is little known how TCF4 plays an important Fig.…”

Section: Activation Of Wnt/β-catenin Signaling In the Dorsal Root Ganmentioning

confidence: 99%

“…Recent studies have shown that Wnt/β-catenin signaling is involved in the development of neuropathic pain. For example, after PSL, expression of Wnt3a, a prototypic Wnt ligand that activates the Wnt/β-catenin pathway, is upregulated in the dorsal horn, which leads to the activation of microglial cells, then triggers BDNF secretion that is responsible for the establishment of neuropathic pain (Itokazu et al 2014). In addition, in postsynaptic neurons, the activation of Wnt/β-catenin signaling could give rise to the cytoplasmic β-catenin accumulation.…”

Section: Activation Of Wnt/β-catenin Signaling In the Dorsal Root Ganmentioning

confidence: 99%

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TCF4 Mediates the Maintenance of Neuropathic Pain Through Wnt/β-Catenin Signaling Following Peripheral Nerve Injury in Rats

Chen

Jiang

et al. 2015

J Mol Neurosci

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Neuropathic pain is elicited after a serious disorder of the nervous system and is along with the neural damage. It is usually chronic and challenging to treat. Transcription factor 4 (TCF4) is a key transcription factor of Wnt signaling system. Recent studies have shown that TCF4 interacts with β-catenin in the Wnt signaling pathway and coactivates downstream target genes in diverse systems. However, it is not well elucidated in the pathogenesis of neuropathic pain. In the present study, we investigated the role of TCF4 in the maintenance of neuropathic pain after chronic constriction injury (CCI) in rats. CCI induced persistent TCF4 upregulation in the dorsal root ganglion and spinal cord. Interestingly, TCF4 was mainly colocalized with neurons in the injured dorsal root ganglion and spinal cord on CCI day 7. Moreover, the expression patterns of β-catenin and glycogen synthase kinase-3β (GSK-3β) were parallel with that of TCF4 in vivo studies. Intrathecal injection of Wnt/β-catenin pathway inhibitor IWR-1-endo and TCF4 small interfering RNA (siRNA) significantly attenuated CCI-induced mechanical allodynia and heat hyperalgesia. The results suggest that TCF4 in the dorsal root ganglion and spinal cord is involved in the maintenance of CCI-induced neuropathic pain. Targeting TCF4 or Wnt/β-catenin signaling may be a potential treatment for chronic neuropathic pain.

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“…BDNF has also been implicated in the etiology of diverse types of neurological disorders (Harte-Hargrove et al 2013), such as depression (Manosso et al 2015; Stuke et al 2012), schizophrenia (Notaras et al 2015; Reinhart et al 2015; Zhang et al 2016), Alzheimer’s disease (AD) (Phillips et al 1991; Tapia-Arancibia et al 2008), Huntington’s disease (HD) (Borrell-Pages et al 2006), and Parkinson’s disease (PD) (L’Episcopo et al 2014). Remarkably, many recent studies have shown that BDNF is emerging as a particularly important player in neuropathic pain (Coull et al 2005; Inoue 2009; Itokazu et al 2014). Chronic pain is a common neurological comorbidity of HIV-1 infection, but the etiological cause and its underlying mechanism remain elusive (Yuan et al 2014).…”

Section: Instructionmentioning

confidence: 99%

HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway

et al. 2017

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HIV-1 gp120 plays a critical role in the pathogenesis of HIV-associated pain, but the underlying molecular mechanisms are incompletely understood. This study aims to determine the effect and possible mechanism of HIV-1 gp120 on BDNF expression in BV2 cells (a murine-derived microglial cell line). We observed that gp120 (10 ng/ml) activated BV2 cells in cultures and upregulated proBDNF/mBDNF. Furthermore, gp120-treated BV2 also accumulated Wnt3a and β-catenin, suggesting the activation of the Wnt/β-catenin pathway. We demonstrated that activation of the pathway by Wnt3a upregulated BDNF expression. In contrast, inhibition of the Wnt/β-catenin pathway by either DKK1 or IWR-1 attenuated BDNF upregulation induced by gp120 or Wnt3a. These findings collectively suggest that gp120 stimulates BDNF expression in BV2 cells via the Wnt/β-catenin signaling pathway.

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Involvement of Wnt/β-catenin signaling in the development of neuropathic pain

Cited by 53 publications

References 38 publications

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal β-catenin in chronic constriction injury rats

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal β-catenin in chronic constriction injury rats

TCF4 Mediates the Maintenance of Neuropathic Pain Through Wnt/β-Catenin Signaling Following Peripheral Nerve Injury in Rats

HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway

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