scholarly journals Nefopam downregulates autophagy and c-Jun N-terminal kinase activity in the regulation of neuropathic pain development following spinal nerve ligation

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Seon-Hee Oh ◽  
Myung Ha Yoon ◽  
Kyung Joon Lim ◽  
Byung Sik Yu ◽  
In Gook Jee ◽  
...  
2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Takayuki Seto ◽  
Hidenori Suzuki ◽  
Tomoya Okazaki ◽  
Yasuaki Imajo ◽  
Norihiro Nishida ◽  
...  

Abstract Background The spinal nerve ligation (SNL) rat is well known as the most common rodent model of neuropathic pain without motor deficit. Researchers have performed analyses using only the von Frey and thermal withdrawal tests to evaluate pain intensity in the rat experimental model. However, these test are completely different from the neurological examinations performed clinically. We think that several behavioral reactions must be observed following SNL because the patients with neuropathic pain usually have impaired coordination of the motions of the right–left limbs and right–left joint motion differences. In this study, we attempted to clarify the pain behavioral reactions in SNL rat model as in patients. We used the Kinema-Tracer system for 3D kinematics gait analysis to identify new characteristic parameters of each joint movement and gait pattern. Results The effect of SNL on mechanical allodynia was a 47 ± 6.1% decrease in the withdrawal threshold during 1–8 weeks post-operation. Sagittal trajectories of the hip, knee and ankle markers in SNL rats showed a large sagittal fluctuation of each joint while walking. Top minus bottom height of the left hip and knee that represents instability during walking was significantly larger in the SNL than sham rats. Both-foot contact time, which is one of the gait characteristics, was significantly longer in the SNL versus sham rats: 1.9 ± 0.15 s vs. 1.03 ± 0.15 s at 4 weeks post-operation (p = 0.003). We also examined the circular phase time to evaluate coordination of the right and left hind-limbs. The ratio of the right/left circular time was 1.0 ± 0.08 in the sham rats and 0.62 ± 0.15 in the SNL rats at 4 weeks post-operation. Conclusions We revealed new quantitative parameters in an SNL rat model that are directly relevant to the neurological symptoms in patients with neuropathic pain, in whom the von Frey and thermal withdrawal tests are not used at all clinically. This new 3D analysis system can contribute to the analysis of pain intensity of SNL rats in detail similar to human patients’ reactions following neuropathic pain.


2020 ◽  
Author(s):  
Chao Xu ◽  
HuiFang Li ◽  
YunPeng Zhang ◽  
TianYu Liu ◽  
Yi Feng

Abstract Background: Neuropathic pain can cause significant physical and economic burden to people, and there are no effective long-term treatment methods for this condition. We conducted a bioinformatics analysis of microarray data to identify related mechanisms to determine strategies for more effective treatments of neuropathic pain.Methods: GSE24982 and GSE63442 microarray datasets were extracted from the Gene Expression Omnibus (GEO) database to analyze transcriptome differences of neuropathic pain in the dorsal root ganglions caused by spinal nerve ligation. We filtered the differentially expressed genes (DEGs) in the two datasets and Webgestalt was applied to conduct GeneOntology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the shared DEGs. String Database and Cytoscape software were used to construct the Protein-Protein Interaction (PPI) network to determine the hub genes, which were subsequently verified in the GSE30691 dataset. Finally, miRDB and miRWalk Databases were used to predict potential miRNA of the selected DEGs.Results: A total of 182 overlapped DEGs were found between GSE24982 and GSE63442 datasets. The GO functional analysis and KEGG enrichment analysis showed that the selected DEGs were mainly enriched in infection, transmembrane transport of ion channels, and synaptic transmission. Combining the results of PPI analysis and the verification of the GSE30691 dataset, we identified seven hub genes related to neuropathic pain (Atf3, Aif1, Ctss, Gfap, Scg2, Jun, and Vgf). Predicted miRNA targeting each selected hub genes were identified.Conclusion: Seven hub genes related to the pathogenesis of neuropathic pain and potential targeting miRNA were identified, expanding understanding of the mechanism of neuropathic pain and facilitating treatment development.


2006 ◽  
Vol 104 (2) ◽  
pp. 328-337 ◽  
Author(s):  
Darren D. O’Rielly ◽  
Christopher W. Loomis

Background Spinal prostaglandins seem to be important in the early pathogenesis of experimental neuropathic pain. Here, the authors investigated changes in the expression of cyclooxygenase and nitric oxide synthase (NOS) isoforms in the lumbar, thoracic, and cervical spinal cord and the pharmacologic sensitivity to spinal prostaglandin E2 (PGE2) after L5-L6 spinal nerve ligation (SNL). Methods Male Sprague-Dawley rats, fitted with intrathecal catheters, underwent SNL or sham surgery 3 days before experimentation. Paw withdrawal threshold was monitored for up to 20 days. Immunoblotting, spinal glutamate release, and behavioral testing were examined 3 days after SNL. Results Allodynia (paw withdrawal threshold < or = 4 g) was evident 1 day after SNL and remained stable for 20 days. Paw withdrawal threshold was unchanged (P > 0.05) from baseline (> 15 g) after sham surgery except for a small but significant decrease on day 20. Cyclooxygenase 2, neuronal NOS, and inducible NOS were significantly increased in the ipsilateral lumbar dorsal horn after SNL. Expression in the contralateral dorsal horn and ventral horns (lumbar segments) or bilaterally (thoracic and cervical segments) was unchanged from sham controls. This was accompanied by a significant decrease in both the EC50 of PGE2-evoked glutamate release and the ED50 of PGE2 on brush-evoked allodynia. Enhanced sensitivity to PGE2 was localized to lumbar segments of SNL animals and attenuated by SC-51322 or S(+)-ibuprofen, but not R(-)-ibuprofen (100 mum). Conclusion The increased expression of cyclooxygense-2, neuronal NOS, and inducible NOS and the enhanced sensitivity to PGE2 in spinal segments affected by SNL support the hypothesis that spinal prostanoids play an early pathogenic role in experimental neuropathic pain.


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