Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice

2015 ◽  
Vol 20 (3) ◽  
pp. 341-352 ◽  
Author(s):  
B. Álvarez-Pérez ◽  
J. Homs ◽  
M. Bosch-Mola ◽  
T. Puig ◽  
F. Reina ◽  
...  
2008 ◽  
Vol 15 (2) ◽  
pp. 27-30
Author(s):  
Sharad Rajpal ◽  
Michael P Steinmetz ◽  
Ahmed A Cheema ◽  
Christopher J Seebruck ◽  
Tiffany A Gerovac ◽  
...  

2007 ◽  
Vol 6 (5) ◽  
pp. 420-424 ◽  
Author(s):  
Sharad Rajpal ◽  
Tiffany A. Gerovac ◽  
Nicholas A. Turner ◽  
Jessica I. Tilghman ◽  
Bradley K. Allcock ◽  
...  

Object The authors previously discovered that genes for the bradykinin-1 (B1) receptor and the transient receptor potential vanilloid subtype 1 (TRPV1) were overexpressed in animals exhibiting thermal hyperalgesia (TH) following spinal cord injury (SCI). They now report the effect of TRPV1 (AMG9810) and B1 (Lys-[Des-Arg9, Leu8]-bradykinin) antagonists on TH in animals following SCI. Methods The rats were subjected to contusion SCI and then divided into groups in which TH did or did not develop. The animals from both groups were given either AMG9810, Lys-(Des-Arg9, Leu8)-bradykinin, or the drug-specific vehicle (control groups). Animals were tested for TH preinjury and at regular intervals after SCI by using the hindlimb withdrawal latency test. Conclusions The administration of AMG9810 likely improves TH as a result of a generalized analgesic effect, whereas the effect of Lys-(Des-Arg9, Leu8)-bradykinin appears more specific to the reversal of TH. This information has potential usefulness in the development of treatment strategies for post-SCI neuropathic pain.


2011 ◽  
Vol 2011 ◽  
pp. 1-24 ◽  
Author(s):  
Mary J. Eaton ◽  
Eva Widerström-Noga ◽  
Stacey Quintero Wolfe

Transplant of cells which make biologic agents that can modulate the sensory and motor responses after spinal cord injury (SCI) would be useful to treat pain and paralysis. To address this need for clinically useful human cells, a unique neuronal cell line that synthesizes and secretes/releases the neurotransmitter serotonin (5HT) was isolated. Hind paw tactile allodynia and thermal hyperalgesia induced by severe contusive SCI were potently reversed after lumbar subarachnoid transplant of differentiated cells, but had no effect on open field motor scores, stride length, foot rotation, base of support, or gridwalk footfall errors associated with the SCI. The sensory effects appeared 1 week after transplant and did not diminish during the 8-week course of the experiment when grafts were placed 2 weeks after SCI. Many grafted cells were still present and synthesizing 5HT at the end of the study. These data suggest that the human neuronal serotonergic hNT2.19 cells can be used as a biologic minipump for receiving SCI-related neuropathic pain, but likely requires intraspinal grafts for motor recovery.


2016 ◽  
pp. 145-153 ◽  
Author(s):  
H. WEI ◽  
Y. WEI ◽  
F. TIAN ◽  
T. NIU ◽  
G. YI

Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Especially, neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effectively therapeutic agents and treatment strategies. Proteinase-activated receptors (PARs) are a family member of G-protein-coupled receptors and are activated by a proteolytic mechanism. One of its subtypes PAR2 has been reported to be engaged in mechanical and thermal hyperalgesia. Thus, in this study we specifically examined the underlying mechanisms responsible for SCI evoked-neuropathic pain in a rat model. Overall, we demonstrated that SCI increases PAR2 and its downstream pathways TRPV1 and TRPA1 expression in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal PAR2 by intrathecal injection of FSLLRY-NH2 significantly inhibits neuropathic pain responses induced by mechanical and thermal stimulation whereas FSLLRY-NH2 decreases the protein expression of TRPV1 and TRPA1 as well as the levels of substance P and calcitonin gene-related peptide. Results of this study have important implications, i.e. targeting one or more of these signaling molecules involved in activation of PAR2 and TRPV1/TRPA1 evoked by SCI may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Rocio Puentes ◽  
Eric P. Knott ◽  
Jaclyn F. Hechtman ◽  
...  

Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain.


2014 ◽  
Vol 14 (6) ◽  
pp. 984-989 ◽  
Author(s):  
Hung Tae Kim ◽  
Taehee Kim ◽  
Brianna Novotny ◽  
Nayab Khan ◽  
James Aksamit ◽  
...  

2017 ◽  
Vol 95 (12) ◽  
pp. 1389-1395 ◽  
Author(s):  
Yan Lv ◽  
Liang Zhang ◽  
Na Li ◽  
Naiken Mai ◽  
Yu Zhang ◽  
...  

Geraniol, a plant-derived monoterpene, has been extensively studied and showed a wide variety of beneficial effects. The aim of this study was to investigate the therapeutic effect of geraniol on functional recovery and neuropathic pain in rats with spinal cord injury (SCI). Rats received a clip-compression SCI and were treated with geraniol 6 h following SCI. Treatment of SCI rats with geraniol markedly improved locomotor function, and reduced sensitivity to the mechanical allodynia and thermal hyperalgesia. Treatment of SCI rats with geraniol increased NeuN-positive cells, suppressed expression of glial fibrillary acidic protein, and reduced activity of caspase-3 in the injured region. Treatment of SCI rats with geraniol reduced levels of malondialdehyde and 3-nitrotyrosine, upregulated protein expression of nuclear factor-erythroid 2-related factor 2 and heme oxygenase 1, and suppressed expression of inducible nitric oxide synthase in the injured region. In addition, treatment of SCI rats with geraniol downregulated protein expression of N-methyl-d-aspartate receptor 1 and reduced the number of CD68-positive cells and protein levels of TNF-α in the injured region. In conclusion, geraniol significantly promoted the recovery of neuronal function and attenuated neuropathic pain after SCI.


2019 ◽  
Vol 27 (3) ◽  
pp. 74-80
Author(s):  
sogol yousefi ◽  
Vida Hojati ◽  
farinaz nasirinezhad ◽  
Fatemeh Ramezani ◽  
Gholamhassan vaezi ◽  
...  

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