scholarly journals The Wnt/β-Catenin Pathway Regulated Cytokines for Pathological Neuropathic Pain in Chronic Compression of Dorsal Root Ganglion Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ye Zhang ◽  
Dan Zhao ◽  
Xutong Li ◽  
Beiyao Gao ◽  
Chengcheng Sun ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Critical Role ◽  
Spinal Cord Dorsal Horn ◽  
Rat Serum ◽  
Tnf Α ◽  
Spinal Cord Dorsal ◽  
Factor Α ◽  
Necrosis Factor

Neuropathic pain is one of the important challenges in the clinic. Although a lot of research has been done on neuropathic pain (NP), the molecular mechanism is still elusive. We aimed to investigate whether the Wnt/β-catenin pathway was involved in NP caused by sustaining dorsal root ganglion (DRG) compression with the chronic compression of dorsal root ganglion model (CCD). Our RNA sequencing results showed that several genes related to the Wnt pathway have changed in DRG and spinal cord dorsal horn (SCDH) after CCD surgery. Therefore, we detected the activation of the Wnt/β-catenin pathway in DRG and SCDH and found active β-catenin significantly upregulated in DRG and SCDH 1 day after CCD surgery and peaked on days 7-14. Immunofluorescence results also confirmed nuclear translocalization of active β-catenin in DRG and SCDH. Additionally, rats had obvious mechanical induced pain after CCD surgery and the pain was significantly alleviated after the application of the Wnt/β-catenin pathway inhibitor XAV939. Furthermore, we found that the levels of proinflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were significantly elevated in CCD rat serum, while the levels of them were correspondingly decreased after the Wnt/β-catenin pathway being inhibited. The results of Spearman correlation coefficient analysis showed that the levels of TNF-α and IL-18 were negatively correlated with the mechanical withdrawal thresholds (MWT) after CCD surgery. Collectively, our findings suggest that the Wnt/β-catenin pathway plays a critical role in the pathogenesis of NP and may be an effective target for the treatment of NP.

scholarly journals Blocking TRPA1 and TNF-α Signal Improves Bortezomib-Induced Neuropathic Pain

2018 ◽  
Vol 51 (5) ◽  
pp. 2098-2110 ◽  
Author(s):  
Chunrui Li ◽  
Taoran Deng ◽  
Zhen Shang ◽  
Di Wang ◽  
Yi Xiao
Keyword(s):  
Neuropathic Pain ◽  
Tumor Necrosis Factor ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Tumor Necrosis ◽  
Cold Sensitivity ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background/Aims: Bortezomib (BTZ) is largely used as a chemotherapeutic agent for the treatment of multiple myeloma. However, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. The purpose of this study was to examine the underlying mechanisms leading to neuropathic pain induced by BTZ. Methods: ELISA and western blot analysis were used to examine the levels of tumor necrosis factor alpha (TNF-α) and its receptor, transient receptor potential ankyrin 1 (TRPA1) and intracellular p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical pain and cold sensitivity in a rat model. Results: Systemic injection of BTZ significantly increased mechanical pain and cold sensitivity as compared with control animals (P< 0.05 vs. control rats). Our data also showed that protein expression of TRPA1 was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical pain and cold sensitivity in control rats and BTZ rats (P< 0.05 vs. vehicle control). Notably, the inhibitory effect of blocking TRPA1 on mechanical pain and cold sensitivity was smaller in BTZ rats than that in control rats. In addition, a blockade of TNF-α attenuated intracellular p38-MAPK and JNK signal in the dorsal root ganglion. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. Conclusion: We revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ. The data also suggest that blocking TRPA1 and tumor necrosis factor alpha is beneficial to alleviate neuropathic pain during BTZ intervention.

scholarly journals Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Javier Sábado ◽  
Anna Casanovas ◽  
Olga Tarabal ◽  
Marta Hereu ◽  
Lídia Piedrafita ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Ventral Horn ◽  
Spinal Cord Dorsal Horn ◽  
Spinal Cord Dorsal ◽  
Neuronal Types ◽  
Misfolded Sod1 ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs). Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations ofsuperoxide dismutase 1(SOD1) gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used theSOD1G93Amouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG) proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

Tumor Necrosis Factor-α-Dependent Infiltration of Macrophages Into the Dorsal Root Ganglion in a Rat Disc Herniation Model

Spine ◽  
2013 ◽  
Vol 38 (23) ◽  
pp. 2003-2007 ◽  
Author(s):  
Changcheng You ◽  
Kai Zhu ◽  
Xiaoqi Liu ◽  
Chunyang Xi ◽  
Zhipeng Zhang ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Dorsal Root Ganglion ◽  
Disc Herniation ◽  
Dorsal Root ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Distribution and Appearance of Tumor Necrosis Factor-α in the Dorsal Root Ganglion Exposed to Experimental Disc Herniation in Rats

Spine ◽  
2004 ◽  
Vol 29 (20) ◽  
pp. 2235-2241 ◽  
Author(s):  
Yasuaki Murata ◽  
Akira Onda ◽  
Björn Rydevik ◽  
Kazuhisa Takahashi ◽  
Kjell Olmarker
Keyword(s):  
Tumor Necrosis Factor ◽  
Dorsal Root Ganglion ◽  
Disc Herniation ◽  
Dorsal Root ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Pulsed Radiofrequency on Dorsal Root Ganglion Improves Neuropathic Pain-induced Depression in SNI Rats by Regulating Hippocampal BDNF and Neuroinflammation via Spinal IRF8 Inactivation

2021 ◽  
Author(s):  
Xueru Xu ◽  
Zhisen Dai ◽  
Chun Lin ◽  
Fan Lin ◽  
Rongguo Liu
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Intrathecal Injection ◽  
Free Water ◽  
Sucrose Preference ◽  
Pulsed Radiofrequency ◽  
Tnf Α ◽  
Immobility Time

Abstract Background: Increasing evidence suggests that neuroglia, neuroimmune, and neuroinflammatory processes are involved in the development of nerve injury-induced pain and depression. Interferon regulatory factor 8 (IRF8), a crucial factor for microglial activation, is essential for the development of neuropathic pain. The brain-derived neurotrophic factor (BDNF) and inflammatory mediators (IL-1β, IL-6, and TNF-α) in the hippocampus contribute to the pathophysiology of neuropathic pain-depression comorbidity. Our previous study found that depressive-like behaviors induced by spared nerve injury (SNI) could be improved by applying pulsed radiofrequency (PRF) to the dorsal root ganglion (DRG) (PRF-DRG). However, the anti-depressive mechanisms of PRF-DRG therapy remain largely unknown. Methods: All rats (except for those in the sham group) were subjected to SNI. The nuclease-free water group and the IRF8 siRNA group were intrathecally injected with nuclease-free water and IRF8 siRNA on days 5 and 6 after SNI, respectively. PRF therapy on the L5 DRG was performed in the PRF group on day 7 after SNI, whereas no PRF current was delivered in the Sham-PRF group. The 50% paw withdrawal threshold, forced swimming test, and sucrose preference test were performed. The expression levels of spinal IRF8 and hippocampal BDNF were tested by molecular biochemistry, while IL-1β, IL-6, and TNF-α were tested by ELISA.Results: The depressive-like behaviors induced by SNI were remarkably developed in rats, which was indicated by a significant reduction in the sucrose preference rate and prolonged immobility time on day 42 after SNI. Mechanical allodynia and depression-like behaviors of rats with SNI were remarkably improved after PRF-DRG or intrathecal IRF8 siRNA. Spinal IRF8 overexpression, hippocampal BDNF downregulation, and increased hippocampal IL-1β and TNF-α levels were reversed by PRF-DRG, similar to the intrathecal injection of IRF8 siRNA. Conclusions: PRF-DRG therapy could regulate neuroimmune and neuroinflammatory responses to improve pain-induced depressive-like behaviors. The beneficial effect was correlated with the upregulation of BDNF and inhibition of IL-1β and TNF-α in the hippocampus via spinal IRF8 inactivation.

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