scholarly journals Electroacupuncture Alleviates Spared Nerve Injury-Induced Neuropathic Pain And Modulates HMGB1/NF-κB Signaling Pathway In The Spinal Cord

2019 ◽  
Vol Volume 12 ◽  
pp. 2851-2863 ◽  
Author(s):  
Yang-yang Xia ◽  
Meng Xue ◽  
Ying Wang ◽  
Zhi-hua Huang ◽  
Cheng Huang
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Nerve Injury ◽  
Spared Nerve Injury

scholarly journals Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats

2020 ◽  
Vol 21 (18) ◽  
pp. 6524
Author(s):  
Meng Xue ◽  
Ya-Lan Sun ◽  
Yang-Yang Xia ◽  
Zhi-Hua Huang ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Inhibitory Effect ◽  
Spared Nerve Injury ◽  
Mechanical Hypersensitivity ◽  
C Fiber ◽  
Wdr Neurons

Neuropathic pain is more complex and severely affects the quality of patients’ life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/TrκB cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and TrκB mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and TrκB expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.

Glucocorticoid receptor inhibit the activity of NF-κB through p38 signaling pathway in spinal cord in the spared nerve injury rats

Life Sciences ◽  
2018 ◽  
Vol 208 ◽  
pp. 268-275 ◽  
Author(s):  
Jinping Shao ◽  
Ruiyan Xu ◽  
Ming Li ◽  
Qingzan Zhao ◽  
Xiuhua Ren ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Glucocorticoid Receptor ◽  
Signaling Pathway ◽  
Nerve Injury ◽  
Spared Nerve Injury

scholarly journals Proteomic analysis of the dorsal spinal cord in the mouse model of spared nerve injury-induced neuropathic pain

2017 ◽  
Vol 31 (6) ◽  
pp. 494 ◽  
Author(s):  
Park Eun-sung ◽  
Ahn Jung-mo ◽  
Jeon Sang-min ◽  
Cho Hee-jung ◽  
Chung Ki-myung ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Mouse Model ◽  
Nerve Injury ◽  
Proteomic Analysis ◽  
Spared Nerve Injury ◽  
Dorsal Spinal Cord ◽  
Dorsal Spinal

scholarly journals Intrathecal IGF2 siRNA injection provides long-lasting anti-allodynic effect in a spared nerve injury rat model of neuropathic pain

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260887
Author(s):  
Wei-Hung Chan ◽  
Nian-Cih Huang ◽  
Yi-Wen Lin ◽  
Feng-Yen Lin ◽  
Chien-Sung Tsai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Protein Expression ◽  
Nerve Injury ◽  
Quantitative Polymerase Chain Reaction ◽  
Response Duration ◽  
Intrathecal Administration ◽  
Significant Inhibition ◽  
Spared Nerve Injury ◽  
Withdrawal Threshold

Previous studies have shown an increase of insulin-like growth factor-2 (IGF2) in animal models of neuropathic pain. We aimed to examine the hypothesis that reducing the expression of IGF2 using intrathecal IGF2 small-interfering RNA (siRNA) would attenuate the development of neuropathic pain in rats after spared nerve injury (SNI). Male Wistar rats were divided into three groups: sham-operated group, in which surgery was performed to cut the muscles without injuring the nerves; SNI group, in which SNI surgery was performed to sever the nerves; and SNI + siRNA IGF2 group, in which SNI surgery was performed, and IGF2-siRNA was administered intrathecally 1 day after SNI. The rats were assessed for mechanical allodynia and cold allodynia 1 day before surgery (baseline), and at 2, 4, 6, 8, and 10 days after siRNA treatment. The rat spinal cord was collected for quantitative polymerase chain reaction and western blot analysis. Compared with the SNI group, rats that received IGF2 siRNA showed a significantly increased SNI-induced paw-withdrawal threshold to metal filament stimulation from Day 4 to Day 10 after SNI surgery. IGF2 siRNA significantly decreased the response duration from the acetone test from Day 2 to Day 10 following SNI surgery. SNI increased IGF2 mRNA expression on Day 2 and increased IGF2 protein expression on Day 8 and Day 10 in the spinal cord of the SNI rats. However, the above-mentioned effects of IGF2 mRNA and protein expression were significantly inhibited in the SNI + IGF2 siRNA group. We demonstrated that intrathecal administration of IGF2 siRNA provided significant inhibition of SNI-induced neuropathic pain via inhibition of IGF2 expression in the spinal cord. The analgesic effect lasted for 10 days. Further exploration of intrathecal IGF2 siRNA administration as a potential therapeutic strategy for neuropathic pain is warranted.

scholarly journals Analysis of Crucial Genes and Pathways Associated with Spared Nerve Injury-Induced Neuropathic Pain

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Dong Mao ◽  
Huang Zhai ◽  
Gang Zhao ◽  
Jingyi Mi ◽  
Yongjun Rui
Keyword(s):  
Transcription Factor ◽  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Nerve Injury ◽  
Microarray Data ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Functional Enrichment ◽  
Spared Nerve Injury ◽  
Ppi Network

Purpose. The study was aimed at elucidating the molecular mechanism underlying neuropathic pain induced by spared nerve injury (SNI). Methods. The microarray data of GSE30691 were downloaded from the Gene Expression Omnibus database, including sciatic nerve lesion samples at 3, 7, 21, and 40 days after SNI and sham control samples at 3, 7, and 21 days. Differential analysis along with Mfuzz clustering analysis was performed to screen crucial clusters and cluster genes. Subsequently, comprehensive bioinformatic analyses were performed, including functional enrichment analysis, protein-protein interaction (PPI) network and module analysis, and transcription factor- (TF-) gene and miRNA-target interaction predictions. Moreover, the screened differentially expressed genes (DEGs) were corroborated using two other microarray datasets. Results. Three clusters with different change trends over time after SNI were obtained. Protein kinase CAMP-activated catalytic subunit beta (Prkacb), complement C3 (C3), and activating transcription factor 3 (Atf3) were hub nodes in the PPI network, and fibroblast growth factor 9 (Fgf9) was found to interact with more TFs. Prkacb and Fgf9 were significantly enriched in the MAPK signaling pathway. Moreover, rno-miR-3583-5p was targeted by Fgf9, and rno-miR-1912-3p was targeted by neuregulin 1 (Nrg1). Key genes like Nrg1 and Fgf9 in cluster 1, Timp1 in cluster 2, and Atf3 and C3 in cluster 3 were screened out after corroborating microarray data with other microarray data. Conclusions. Key pathways like the MAPK signaling pathway and crucial genes like Prkacb, Nrg1, Fgf9, Timp1, C3, and Atf3 may contribute to SNI-induced neuropathic pain development in rats.

scholarly journals Spinal cord stimulation using differential target multiplexed programming modulates neural cell-specific transcriptomes in an animal model of neuropathic pain

2020 ◽  
Vol 16 ◽  
pp. 174480692096436
Author(s):  
David L Cedeño ◽  
William J Smith ◽  
Courtney A Kelley ◽  
Ricardo Vallejo
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Neural Cell ◽  
High Rate ◽  
Spared Nerve Injury ◽  
Expression Levels ◽  
Injury Model ◽  
Low Rate

Spinal cord stimulation is a proven effective therapy for treating chronic neuropathic pain. Previous work in our laboratory demonstrated that spinal cord stimulation based on a differential target multiplexed programming approach provided significant relief of pain-like behavior in rodents subjected to the spared nerve injury model of neuropathic pain. The relief was significantly better than obtained using high rate and low rate programming. Furthermore, transcriptomics-based results implied that differential target multiplexed programming modulates neuronal–glial interactions that have been perturbed by the pain process. Although differential target multiplexed programming was developed to differentially target neurons and glial cells, our previous work did not address this. This work presents transcriptomes, specific to each of the main neural cell populations (neurons, microglia, astrocytes, and oligodendrocytes), obtained from spinal cord subjected to continuous spinal cord stimulation treatment with differential target multiplexed programming, high rate programming, or low rate programming compared with no spinal cord stimulation treatment, using the spared nerve injury model. To assess the effect of each spinal cord stimulation treatment on these cell-specific transcriptomes, gene expression levels were compared with that of healthy animals, naïve to injury and interventional procedures. Pearson correlations and cell population analysis indicate that differential target multiplexed programming yielded strong and significant correlations to expression levels found in the healthy animals across every evaluated cell-specific transcriptome. In contrast, high rate programming only yielded a strong correlation for the microglia-specific transcriptome, while low rate programming did not yield strong correlations with any cell types. This work provides evidence that differential target multiplexed programming distinctively targeted and modulated the expression of cell-specific genes in the direction of the healthy state thus supporting its previously established action on regulating neuronal–glial interaction processes in a pain model.

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