View : 154 Download: 0

HYP-17, a novel voltage-gated sodium channel blocker, relieves inflammatory and neuropathic pain in rats

Title
HYP-17, a novel voltage-gated sodium channel blocker, relieves inflammatory and neuropathic pain in rats
Authors
Lee, Jee YounKam, Yoo LimOh, JungaeKim, Dong HyunChoi, Jin-SungChoi, Hae YoungHan, SungminYoun, InchanChoo, Hea-Young ParkYune, Tae Young
Ewha Authors
박혜영
SCOPUS Author ID
박혜영scopus
Issue Date
2017
Journal Title
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
ISSN
0091-3057JCR Link
Citation
vol. 153, pp. 116 - 129
Keywords
Sodium channel inhibitorSpinal cord injuryTail nerve injuryNeuropathic painMicrogliaAstrocyte
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Clinical and experimental studies suggest that voltage-gated sodium channels (VGSCs) play a key role in the pathogenesis of neuropathic pain and that blocking agents against these channels can be potentially therapeutic. In the current study, we investigated whether a novel compound, (-)-2-Amino-1-(4-( (4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-propan-1-one(HYP-17), binds to VGSCs and evaluated its inhibitory effect on Na+ currents of the rat dorsal root ganglia (DRG) sensory neurons and its analgesic effect on inflammatory and neuropathic pain. HYP-17 (10 mu M) reduced both the tetrodotoxin-sensitive (TTX-S) and the TTX-resistant (TTX-R) currents in DRG sensory neurons. However, neither the voltage-dependent activation curves nor the steady-state inactivation curves for TTX-S and TTX-R currents were changed by HYP-17. In rats injected with 5% formalin under the plantar surface of the hind paw, HYP-17 (10 mu g) significantly reduced both the early and late phase spontaneous pain behaviors. Systemic injection with HYP-17 (60 mg/kg, i.p.) also significantly relieved the mechanical, cold, and warm allodynia induced by rat tail nerve injury. Furthermore, HYP-17 (60 mg/kg, i.p.) significantly relieved the central neuropathic pain induced by spinal cord injury (SCI), and inhibited c-Fos expression in lumbar (L) 4-L5 spinal segments. Electrophysiological study showed that HYP-17 significantly attenuated the hyper-responsiveness of lumbar dorsal horn neurons. In addition, HYP-17 significantly reduced the levels of pp38MAPK and p-JNK in microglia and astrocytes, respectively, in the L4-L5 spinal dorsal horn. Therefore, our results indicate that HYP-17 has potential analgesic activities against nociceptive, inflammatory and neuropathic pain. (C) 2016 Published by Elsevier Inc.
DOI
10.1016/j.pbb.2016.12.013
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE