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Intrathecal Injection of the [final sigma]1 Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression during the Induction Phase of Rodent Neuropathic Pain

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Authors
Roh, Dae-Hyun; Kim, Hyun-Woo; Yoon, Seo Yeon; Seo, Hyoung-Sig; Kwon, Young-Bae; Kim, Kee-Won; Han, Ho-Jae; Beitz, Alvin J.; Na, Heung-Sik; Lee, Jang-Hern
Issue Date
2008
Publisher
Lippincott, Williams & Wilkins
Citation
Anesthesiology 2008; 109:879-89
Abstract
Background: Selective blockade of spinal 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.
ISSN
0003-3022
Language
English
URI
http://hdl.handle.net/10371/8595
DOI
https://doi.org/10.1097/ALN.0b013e3181895a83
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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