Minocycline prevents impaired glial glutamate uptake in the spinal sensory synapses of neuropathic rats.

Abstract

Activation of glutamate receptors and glial cells in the spinal dorsal horn are two fundamental processes involved in the pathogenesis of various pain conditions, including neuropathic pain induced by injury to the peripheral or central nervous systems. Numerous studies have demonstrated that minocycline treatment attenuates allodynic and hyperalgesic behaviors induced by tissue inflammation or nerve injury. However, the synaptic mechanisms by which minocycline prevents hyperalgesia are not fully understood. We recently reported that deficient glutamate uptake by glial glutamate transporters (GTs) is key for the enhanced activation of N-methyl-d-aspartate (NMDA) receptors in the spinal sensory synapses of rats receiving partial sciatic nerve ligation (pSNL). In this study, we investigated how minocycline affects activation of NMDA receptors in the spinal sensory synapses in rats with pSNL by whole cell recordings of NMDA currents in spinal laminea I and II neurons from spinal slices. The effects of minocycline treatments on the dorsal horn expression of glial GTs and astrocyte marker glial fibrillary acidic protein (GFAP) were analyzed by immunohistochemistry. We demonstrated that normalized activation of NMDA receptors in synapses activated by both weak and strong peripheral input in the spinal dorsal horn is temporally associated with attenuated mechanical allodynia in rats with pSNL receiving intraperitoneal injection of minocycline. Minocycline ameliorated both the downregulation of glial GT expression and the activation of astrocytes induced by pSNL in the spinal dorsal horn. We further revealed that preventing deficient glial glutamate uptake at the synapse is crucial for preserving the normalized activation of NMDA receptors in the spinal sensory synapses in pSNL rats treated with minocycline. Our studies suggest that glial GTs may be a potential target for the development of analgesics.

• Authors: H Nie, H Zhang, H R Weng
• Journal: Neuroscience (Neuroscience) Vol. 170 Issue 3 Pg. 901-12 (Oct 27 2010) ISSN: 1873-7544 [Electronic] United States
• PMID: 20678556 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Amino Acid Transport System X-AG
• Glial Fibrillary Acidic Protein
• Minocycline

Topics

• Amino Acid Transport System X-AG (metabolism)
• Animals
• Disease Models, Animal
• Down-Regulation (drug effects)
• Glial Fibrillary Acidic Protein (metabolism)
• Hyperalgesia (physiopathology, prevention & control)
• Ligation
• Male
• Minocycline (pharmacology, therapeutic use)
• Neuralgia (drug therapy)
• Neuroglia (drug effects, metabolism)
• Patch-Clamp Techniques
• Rats
• Rats, Sprague-Dawley
• Sciatic Nerve (surgery)
• Sensory Receptor Cells (pathology, physiology)
• Spinal Cord (drug effects, metabolism, physiopathology)
• Synapses (physiology)