Biomol Ther (Seoul)  
Intravenous Administration of Substance P Attenuates Mechanical Allodynia Following Nerve Injury by Regulating Neuropathic Pain-Related Factors
Eunkyung Chung1,†, Tae Gyoon Yoon2,†, Sumin Kim3, Moonkyu Kang4, Hyun Jeong Kim4,* and Youngsook Son3,*
1BIO R&D Center, L&K BIOMED CO., LTD., Seoul 08512,
2Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul 05030,
3Department of Genetic Engineering, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yongin 17104,
4Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea
E-mail: dentane@snu.ac.kr (Kim HJ), ysson@khu.ac.kr (Son Y)
Tel: +82-2-2072-3847 (Kim HJ), +82-31-201-2151 (Son Y)
Fax: +82-2-766-9427 (Kim HJ), +82-31-204-8117 (Son Y)
The first two authors contributed equally to this work.
Received: June 23, 2016; Revised: August 19, 2016; Accepted: October 13, 2016; Published online: December 16, 2016.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey’s test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4-L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.
Keywords: Mechanical allodynia, GFAP, IL-10, Neuropathic pain, Substance P, Glial inactivation


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