| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lee, Jee Youn Kam, Yoo Lim Oh, Jungae Kim, Dong Hyun Choi, Jin-Sung Choi, Hae Young Han, Sungmin Youn, Inchan Choo, Hea-Young Park Yune, Tae Young |
| Description |
Author Affiliation: Lee JY ( Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Republic of Korea.); Kam YL ( School of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.); Oh J ( School of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.); Kim DH ( College of Pharmacy, The Catholic University of Korea, Gyeonggi-do, 14662, Republic of Korea.); Choi JS ( College of Pharmacy, The Catholic University of Korea, Gyeonggi-do, 14662, Republic of Korea.); Choi HY ( Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Republic of Korea.); Han S ( Department of Biomedical Science, College of Medicine, Korea University, Seoul, 02841, Republic of Korea.); Youn I ( Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.); Choo HP ( School of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address: hypark@ewha.ac.kr.); Yune TY ( Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Republic of Korea) |
| 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 (10µM) 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 (10µg) significantly reduced both the early and late phase spontaneous pain behaviors. Systemic injection with HYP-17 (60mg/kg, i.p.) also significantly relieved the mechanical, cold, and warm allodynia induced by rat tail nerve injury. Furthermore, HYP-17 (60mg/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. |
| File Format |
HTM / HTML |
| ISSN |
00913057 |
| Journal |
Pharmacology Biochemistry and Behavior |
| Volume Number |
153 |
| e-ISSN |
18735177 |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2017-02-01 |
| Publisher Place |
United States |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Behavioral Sciences Discipline Biochemistry Discipline Pharmacology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Biological Psychiatry Behavioral Neuroscience Biochemistry Clinical Biochemistry Toxicology Pharmacology |
