Biomol Ther.  2017 May;25(3):259-265. 10.4062/biomolther.2016.137.

Intravenous Administration of Substance P Attenuates Mechanical Allodynia Following Nerve Injury by Regulating Neuropathic Pain-Related Factors

• Chung E
• Yoon TG
• Kim S
• Kang M
• Kim HJ
• Son Y

• KMID: 2378803
• DOI: http://doi.org/10.4062/biomolther.2016.137

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.

Keyword

Mechanical allodynia; GFAP; IL-10; Neuropathic pain; Substance P; Glial inactivation

MeSH Terms

Administration, Intravenous*
Animals
Behavior Rating Scale
Biomarkers
Constriction
Glial Fibrillary Acidic Protein
Humans
Hyperalgesia*
Interleukin-10
Mice
Mice, Inbred ICR
Models, Animal
Models, Theoretical
Neuralgia
Neuroglia
Spinal Cord
Spinal Cord Dorsal Horn
Substance P*
Biomarkers
Glial Fibrillary Acidic Protein
Interleukin-10
Substance P