scholarly journals Astrocyte-neuron interaction in the substantia gelatinosa of the spinal cord dorsal horn via P2X7 receptor-mediated release of glutamate and reactive oxygen species

Glia ◽  
2014 ◽  
Vol 62 (10) ◽  
pp. 1671-1686 ◽  
Author(s):  
Christoph Ficker ◽  
Katalin Rozmer ◽  
Erzsébet Kató ◽  
Rómeó D. Andó ◽  
Luisa Schumann ◽  
...  
2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hee Young Kim ◽  
Inhyung Lee ◽  
Sang Woo Chun ◽  
Hee Kee Kim

Our previous studies suggest that reactive oxygen species (ROS) scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing eitherOH∙,OCl-, or H2O2were examined on pain behaviors. Following treatment witht-BOOH (OH∙donor), dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG) neurons using whole-cell patch clamping recordings. Intrathecal administration oft-BOOH or NaOCl (OCl-donor), but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application oft-BOOH. Thet-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especiallyOH∙, in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats.


Neuron ◽  
2014 ◽  
Vol 81 (6) ◽  
pp. 1443 ◽  
Author(s):  
Rita Bardoni ◽  
Vivianne L. Tawfik ◽  
Dong Wang ◽  
Amaury François ◽  
Carlos Solorzano ◽  
...  

2007 ◽  
Vol 55 (2) ◽  
pp. 158-166 ◽  
Author(s):  
D SINISCALCO ◽  
C FUCCIO ◽  
C GIORDANO ◽  
F FERRARACCIO ◽  
E PALAZZO ◽  
...  

2008 ◽  
Vol 109 (5) ◽  
pp. 879-889 ◽  
Author(s):  
Dae-Hyun Roh ◽  
Hyun-Woo Kim ◽  
Seo-Yeon Yoon ◽  
Hyoung-Sig Seo ◽  
Young-Bae Kwon ◽  
...  

Background Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain. Methods Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats. Results BD1047 administered on postoperative days 0-5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation. Conclusions These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.


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