scholarly journals Three-dimensional analysis of the characteristics of joint motion and gait pattern in a rodent model following spinal nerve ligation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Takayuki Seto ◽  
Hidenori Suzuki ◽  
Tomoya Okazaki ◽  
Yasuaki Imajo ◽  
Norihiro Nishida ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Pain Intensity ◽  
Rat Model ◽  
Gait Pattern ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Joint Motion ◽  
Behavioral Reactions ◽  
Post Operation ◽  
The Right

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.

scholarly journals The Effect of Epidural Resiniferatoxin in the Neuropathic Pain Rat Model

2012 ◽  
Vol 4;15 (4;8) ◽  
pp. 287-296
Author(s):  
Mi Kyoung Lee
Keyword(s):  
Neuropathic Pain ◽  
Rat Model ◽  
Analgesic Effect ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Thermal Stimulation ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Epidural Administration ◽  
Mechanical Hypersensitivity

Background: Resiniferatoxin (RTX) is a potent synthetic agonist for transient receptor potential vanilloid subtype 1 (TRPV1), which has a selectivity for antinociception. The analgesic effect of epidural RTX in a rat model of neuropathic pain has not yet been studied. Objectives: The purpose of this study was to evaluate the analgesic effect of epidural RTX on neuropathic pain in a rat model to mechanical and thermal stimulation. The dose-related behavior changes and side effects were also studied. Study design: A randomized, experimental trial. Setting: Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital Methods: A spinal nerve ligation model was prepared using male Sprague-Dawley rats (7 weeks old, weight 230-250 g). An epidural catheter was placed at the L4-L5 level. Each study group (n = 6) received a different dose of RTX: 100 ng, 500 ng, 1 µg, 2 µg, 4 µg and 10 µg. All substances were administered in 20 µL volume doses. The control group (n = 6) received 20 µL of normal saline. We evaluated the response to mechanical and thermal stimuli as well as the sedation score at both short-term (3 hours) and long-term (20 days) after the epidural RTX injection. Results: Prolonged analgesia to thermal stimulation was preceded by a transient dose-dependent hyperalgesia (500 ng, 1 µg) or sedation (≥ 2 µg) during the initial 60 minutes after RTX administration. Marked sedation and hyperventilation were noted at higher doses (≥ 2 µg), while 2 out of 6 rats died with a 10 µg dose. ED50 for epidural RTX was 265 ng (95% confidence interval 216.1–324.9 ng). The increased latency to thermal stimulation continued for 20 days at RTX ≥ 1 µg. But the threshold to mechanical stimulation increased only in the acute period and returned to the baseline after 3-5 days, regardless of the administered dose. Limitations: A histological examination by electron-microscopic staining was not performed. The observation period was not very long (20 days). Conclusion: RTX has potential to be used in an epidural route for neuropathic pain in a rat model with a relatively small amount, which produces transitory improvement of mechanical hypersensitivity and prolonged thermal analgesic response. Key words: Epidural administration, mechanical allodynia, mechanical hypersensitivity, resiniferatoxin, sedation, spinal nerve ligation rat model, thermal hyperalgesia.

scholarly journals Biomarker Analysis of Orally Dosed, Dual Active, Matrix Metalloproteinase (MMP)-2 and MMP-9 Inhibitor, AQU-118, in the Spinal Nerve Ligation (SNL) Rat Model of Neuropathic Pain

2019 ◽  
Vol 20 (4) ◽  
pp. 811 ◽  
Author(s):  
Mei Kwan ◽  
Anthony Choo ◽  
Taleen Hanania ◽  
Afshin Ghavami ◽  
Jose Beltran ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Rat Model ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Caspase 3 ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Oral Dosing ◽  
Protein Levels

There is an unmet medical need for the development of non-addicting pain therapeutics with enhanced efficacy and tolerability. The current study examined the effects of AQU-118, an orally active inhibitor of metalloproteinase-2 (MMP-2) and MMP-9, in the spinal nerve ligation (SNL) rat model of neuropathic pain. Mechanical allodynia and the levels of various biomarkers were examined within the dorsal root ganglion (DRG) before and after oral dosing with AQU-118. The rats that received the SNL surgery exhibited significant mechanical allodynia as compared to sham controls. Animals received either vehicle, positive control (gabapentin), or AQU-118. After SNL surgery, the dorsal root ganglion (DRG) of those rats dosed with vehicle had elevated messenger RNA (mRNA) expression levels for MMP-2, IL1-β & IL-6 and elevated protein levels for caspase-3 while exhibiting decreased protein levels for myelin basic protein (MBP) & active IL-β as compared to sham controls. Rats orally dosed with AQU-118 exhibited significantly reduced mechanical allodynia and decreased levels of caspase-3 in the DRG as compared to vehicle controls. Results demonstrate that oral dosing with the dual active, MMP-2/-9 inhibitor, AQU-118, attenuated mechanical allodynia while at the same time significantly reduced the levels of caspase-3 in the DRG.

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 ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Kinase Activity ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation

Comprehensive Analysis of Differentially Expressed Genes and Key Pathways in Neuropathic Pain by Spinal Nerve Ligation

2020 ◽  
Author(s):  
Chao Xu ◽  
HuiFang Li ◽  
YunPeng Zhang ◽  
TianYu Liu ◽  
Yi Feng
Keyword(s):  
Functional Analysis ◽  
Neuropathic Pain ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Long Term Treatment

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.

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