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Changes in electrophysiological properties and sodium channel Nav1.3 expression in thalamic neurons after spinal cord injury.
- Source :
-
Brain : a journal of neurology [Brain] 2005 Oct; Vol. 128 (Pt 10), pp. 2359-71. Date of Electronic Publication: 2005 Aug 18. - Publication Year :
- 2005
-
Abstract
- Spinal cord contusion injury (SCI) is known to induce pain-related behaviour, as well as hyperresponsiveness in lumbar dorsal horn nociceptive neurons associated with the aberrant expression of Na(v)1.3, a rapidly repriming voltage-gated sodium channel. Many of these second-order dorsal horn neurons project to third-order neurons in the ventrobasal complex of the thalamus. In this study we hypothesized that, following SCI, neurons in the thalamus undergo electrophysiological changes linked to aberrant expression of Na(v)1.3. Adult male Sprague-Dawley rats underwent contusion SCI at the T9 thoracic level. Four weeks post-SCI, Na(v)1.3 protein was upregulated within thalamic neurons in ventroposterior lateral (VPL) and ventroposterior medial nuclei, where extracellular unit recordings revealed increased spontaneous discharge, afterdischarge, hyperresponsiveness to innocuous and noxious peripheral stimuli, and expansion of peripheral receptive fields. Altered electrophysiological properties of VPL neurons persisted after interruption of ascending spinal barrage by spinal cord transection above the level of the injury. Lumbar intrathecal administration of specific antisense oligodeoxynucleotides generated against Na(v)1.3 caused a significant reduction in Na(v)1.3 expression in thalamic neurons and reversed electrophysiological alterations. These results show, for the first time, a change in sodium channel expression within neurons in the thalamus after injury to the spinal cord, and suggest that these changes contribute to altered processing of somatosensory information after SCI.
- Subjects :
- Action Potentials physiology
Animals
Behavior, Animal
Evoked Potentials physiology
Immunohistochemistry methods
Lateral Thalamic Nuclei metabolism
Male
NAV1.3 Voltage-Gated Sodium Channel
Nerve Tissue Proteins analysis
Oligonucleotides, Antisense genetics
Rats
Rats, Sprague-Dawley
Sodium Channels analysis
Spinal Cord Injuries genetics
Spinal Cord Injuries metabolism
Thoracic Vertebrae
Up-Regulation
Ventral Thalamic Nuclei metabolism
Nerve Tissue Proteins metabolism
Neurons metabolism
Sodium Channels metabolism
Spinal Cord Injuries physiopathology
Thalamus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2156
- Volume :
- 128
- Issue :
- Pt 10
- Database :
- MEDLINE
- Journal :
- Brain : a journal of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 16109750
- Full Text :
- https://doi.org/10.1093/brain/awh623