The critical role of spinal ceramide in the development of partial sciatic nerve ligation-induced neuropathic pain in mice.

Abstract

Recent observations indicate that peripheral nerve injury induces central sensitization through microglial activation and the release of inflammatory cytokines, resulting in the development of neuropathic pain. However, the underlying mechanisms of this phenomenon remain to be fully elucidated. In this study, we examined the involvement of spinal ceramide, a bioactive lipid, in the development of neuropathic pain induced by partial sciatic nerve ligation (PSL). We found that the mRNA expression levels for ceramide synthase and neutral sphingomyelinase, which are enzymes of ceramide biosynthesis, were up-regulated in the spinal cord from 3h to 1 day after PSL. The mRNA expressions of cytokines (interleukin-1β and tumor necrosis factor-α) and the microglial specific molecules (Iba-1 and CD11b) were also increased in the spinal cord after PSL. In the von Frey test, intrathecal injection of the ceramide biosynthesis inhibitors Fumonisin B1 and GW4869 at 3h and day 3 after PSL significantly attenuated PSL-induced tactile allodynia. By immunohistochemistry, microglial activation in the dorsal horn was suppressed by Fumonisin B1 and GW4869. Therefore, we conclude that spinal ceramide may play a crucial role in PSL-induced neuropathic pain through the activation of microglia.

• Authors: Yuka Kobayashi, Norikazu Kiguchi, Takehiko Maeda, Masanobu Ozaki, Shiroh Kishioka
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 421 Issue 2 Pg. 318-22 (May 04 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22503971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Aniline Compounds
• Benzylidene Compounds
• Ceramides
• Cytokines
• Fumonisins
• GW 4869
• RNA, Messenger
• fumonisin B1
• Oxidoreductases
• dihydroceramide desaturase
• Sphingomyelin Phosphodiesterase

Topics

• Aniline Compounds (pharmacology)
• Animals
• Benzylidene Compounds (pharmacology)
• Ceramides (metabolism)
• Cytokines (biosynthesis)
• Fumonisins (pharmacology)
• Hyperalgesia (metabolism)
• Ligation
• Male
• Mice
• Mice, Inbred ICR
• Microglia (drug effects, metabolism)
• Neuralgia (metabolism)
• Oxidoreductases (antagonists & inhibitors, genetics, metabolism)
• Peripheral Nerve Injuries (metabolism)
• RNA, Messenger (genetics, metabolism)
• Sciatic Nerve (injuries, metabolism)
• Sphingomyelin Phosphodiesterase (antagonists & inhibitors, genetics, metabolism)
• Spinal Cord (drug effects, metabolism)