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Minocycline prevents impaired glial glutamate uptake in the spinal sensory synapses of neuropathic rats.
- Source :
-
Neuroscience [Neuroscience] 2010 Oct 27; Vol. 170 (3), pp. 901-12. Date of Electronic Publication: 2010 Aug 03. - Publication Year :
- 2010
-
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.<br /> (Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Transport System X-AG metabolism
Animals
Disease Models, Animal
Down-Regulation drug effects
Glial Fibrillary Acidic Protein metabolism
Hyperalgesia physiopathology
Ligation
Male
Neuroglia metabolism
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Sciatic Nerve surgery
Sensory Receptor Cells pathology
Spinal Cord metabolism
Spinal Cord physiopathology
Synapses physiology
Hyperalgesia prevention & control
Minocycline pharmacology
Minocycline therapeutic use
Neuralgia drug therapy
Neuroglia drug effects
Sensory Receptor Cells physiology
Spinal Cord drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 170
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 20678556
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2010.07.049