scholarly journals Impact of gabapentin on neuronal high voltage-activated Ca2+ channel properties of injured-side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation

2017 ◽  
Vol 13 (3) ◽  
pp. 851-860 ◽  
Author(s):  
Minmin Zhu ◽  
Xiaodi Sun ◽  
Xiaodong Chen ◽  
Hang Xiao ◽  
Manlin Duan ◽  
...  
2019 ◽  
Vol 20 (4) ◽  
pp. 811 ◽  
Author(s):  
Mei Kwan ◽  
Anthony Choo ◽  
Taleen Hanania ◽  
Afshin Ghavami ◽  
Jose Beltran ◽  
...  

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.


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.


IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S348
Author(s):  
Jaisan Islam ◽  
Elina Kc ◽  
Hyeong Cheol Moon ◽  
Kyoung Ha So ◽  
Sang Hwan Hyun ◽  
...  

2008 ◽  
Vol 1219 ◽  
pp. 26-31 ◽  
Author(s):  
Megumi Omori ◽  
Masataka Yokoyama ◽  
Yoshikazu Matsuoka ◽  
Hiroyuki Kobayashi ◽  
Satoshi Mizobuchi ◽  
...  

2001 ◽  
Vol 93 (2) ◽  
pp. 164-172 ◽  
Author(s):  
Jiangang Xie ◽  
Young Ho Lee ◽  
Chen Wang ◽  
Jin Mo Chung ◽  
Kyungsoon Chung

Pain ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Tetsuo Fukuoka ◽  
Hiroki Yamanaka ◽  
Kimiko Kobayashi ◽  
Masamichi Okubo ◽  
Kan Miyoshi ◽  
...  

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