scholarly journals Electroacupuncture Treatment Suppresses Transcription Factor IRF8 in Spinal Cord of Rats with Spared Nerve Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Wang ◽  
Meng Xue ◽  
Yang-yang Xia ◽  
Qian Jiang ◽  
Zhi-hua Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Transcription Factor ◽  
Neuropathic Pain ◽  
Protein Expression ◽  
Nerve Injury ◽  
Microglial Activation ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Spared Nerve Injury ◽  
Mrna And Protein Expression

Objective. Neuropathic pain with complex mechanisms has become a major public health problem that greatly impacts patients’ quality of life. Therefore, novel and more effective strategies against neuropathic pain need further investigation. Electroacupuncture (EA) has an ameliorating effect on neuropathic pain following spared nerve injury (SNI), but the underlying mechanism remains to be fully clarified. Interferon regulatory factor 8 (IRF8), a critical transcription factor, was reported to be involved in the modulation of neuropathic pain. Here, we focused on exploring whether 2 Hz EA stimulation exerts an inhibitory action on spinal IRF8 in SNI rats. Methods. In this study, SNI rats were treated with 2 Hz EA once every other day for 21 days. Paw withdrawal threshold (PWT) was applied to determine the analgesic effect of 2 Hz EA on SNI rats. The spinal IRF8 and CX3CRl expressions were detected with qRT-PCR and western blot, and immunofluorescence staining was used to evaluate colocation of IRF8 or CX3CRl with microglial activation marker CD11b in the spinal cord. Results. It was found that SNI induced significant elevation of spinal IRF8 and CX3CRl mRNA and protein expression. Additionally, immunofluorescence results showed that SNI elicited the coexpression of IRF8 with CD11b, as well as CX3CRl with CD11b in the spinal cord. Meanwhile, 2 Hz EA treatment of SNI rats not only reduced IRF8 and CX3CRl mRNA and protein expression, but also reversed the coexpression of IRF8 or CX3CRl with CD11b in the spinal cord, along with an attenuation of SNI-evoked mechanical hypersensitivity. Conclusion. This experiment highlighted that 2 Hz EA can inhibit IRF8 expression and microglial activation in the spinal cord of SNI rats. Hence, targeting IRF8 may be a promising therapeutic strategy for 2 Hz EA treatment of neuropathic pain.

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 Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

2020 ◽  
Vol 21 (7) ◽  
pp. 2390
Author(s):  
Masamichi Shinoda ◽  
Satoshi Fujita ◽  
Shiori Sugawara ◽  
Sayaka Asano ◽  
Ryo Koyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Microglial Activation ◽  
In Vivo Optical Imaging ◽  
Stimulation Of

We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following 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 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.

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.

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