Changes in VGLUT2 expression and function in pain-related supraspinal regions correlate with the pathogenesis of neuropathic pain in a mouse spared nerve injury model.

Abstract

Vesicular glutamate transporters (VGLUTs) control the storage and release of glutamate, which plays a critical role in pain processing. The VGLUT2 isoform has been found to be densely distributed in the nociceptive pathways in supraspinal regions, and VGLUT2-deficient mice exhibit an attenuation of neuropathic pain; these results suggest a possible involvement of VGLUT2 in neuropathic pain. To further examine this, we investigated the temporal changes in VGLUT2 expression in different brain regions as well as changes in glutamate release from thalamic synaptosomes in spared nerve injury (SNI) mice. We also investigated the effects of a VGLUT inhibitor, Chicago Sky Blue 6B (CSB6B), on pain behavior, c-Fos expression, and depolarization-evoked glutamate release in SNI mice. Our results showed a significant elevation of VGLUT2 expression up to postoperative day 1 in the thalamus, periaqueductal gray, and amygdala, followed by a return to control levels. Consistent with the changes in VGLUT2 expression, SNI enhanced depolarization-induced glutamate release from thalamic synaptosomes, while CSB6B treatment produced a concentration-dependent inhibition of glutamate release. Moreover, intracerebroventricular administration of CSB6B, at a dose that did not affect motor function, attenuated mechanical allodynia and c-Fos up-regulation in pain-related brain areas during the early stages of neuropathic pain development. These results demonstrate that changes in the expression of supraspinal VGLUT2 may be a new mechanism relevant to the induction of neuropathic pain after nerve injury that acts through an aggravation of glutamate imbalance.

• Authors: Zhi-Tong Wang, Gang Yu, Hong-Sheng Wang, Shou-Pu Yi, Rui-Bin Su, Ze-Hui Gong
• Journal: Brain research (Brain Res) Vol. 1624 Pg. 515-524 (Oct 22 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 26300222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Coloring Agents
• Proto-Oncogene Proteins c-fos
• Vesicular Glutamate Transport Protein 2
• pontamine sky blue
• Glutamic Acid
• Trypan Blue

Topics

• Animals
• Brain (metabolism, pathology)
• Coloring Agents (pharmacology)
• Disease Models, Animal
• Gene Expression Regulation (drug effects, physiology)
• Glutamic Acid (metabolism)
• Hyperalgesia (physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Motor Activity (drug effects)
• Neuralgia (pathology, physiopathology)
• Proto-Oncogene Proteins c-fos (metabolism)
• Spinal Cord (metabolism, pathology)
• Statistics, Nonparametric
• Synaptosomes (metabolism, pathology)
• Tibial Nerve (injuries, physiopathology)
• Trypan Blue (pharmacology)
• Vesicular Glutamate Transport Protein 2 (antagonists & inhibitors, metabolism)