The role of ionotropic glutamate receptors in chronic central pain after spinal cord injury
| dc.contributor.advisor | Claire Hulsebosch, Ph.D. | en_US |
| dc.contributor.committeeMember | William D. Willis, M.D./Ph.D. | en_US |
| dc.contributor.committeeMember | Volker E. Neugebauer, M.D./Ph.D. | en_US |
| dc.contributor.committeeMember | Martin Grabois, M.D. | en_US |
| dc.contributor.committeeMember | B. Mark Evers, M.D. | en_US |
| dc.creator | Huaiyu Tan | en_US |
| dc.date.accessioned | 2011-12-20T16:05:45Z | |
| dc.date.available | 2009-06-09 | en_US |
| dc.date.available | 2011-12-20T16:05:45Z | |
| dc.date.created | 2005-12-21 | en_US |
| dc.date.issued | 2005-12-12 | en_US |
| dc.description.abstract | Spinal cord injury (SCI) results in both loss of function and chronic central pain syndromes. In the clinical population, pain is characterized based on anatomical location: 1) Below-level pain – located at dermatomes corresponding to spinal segments caudal to the injury site, 2) At-level pain – located at dermatomes corresponding to spinal segments immediately adjacent to the injury site, 3) Above-level pain – located at segments rostral to the injury site (in area of sensory preservation). \r\n A contusion model of SCI was first characterized behaviorally and electrophysiologically. A contusion at spinal segment T10 at 150 kdynes of force and a 1 second dwell time resulted in the pain like behavior in the hindlimbs, thoracic region, and forelimbs 35 days post-injury. These contused animals exhibited spinal hyperexcitability during extracellular single-unit electrophysiological spinal recordings from the dorsal horn of the lumbar enlargement (below-level), thoracic cord (at-level; immediately rostral to injury site), and brachial enlargement (above level). \r\n In models of peripheral injury, increased ionotropic glutamate receptor mediated activity results in spinal central sensitization. Extracellular single-unit recordings from all three regions of the spinal cord (lumbar enlargement, thoracic cord, and brachial enlargement) were made on both contused and non-contused animals during ionotropic glutamate antagonist treatment (D-AP5 or NBQX). The thoracic cord, which is nearest to the site of injury, showed the greatest increase in ionotropic glutamate receptor mediated activity. \r\n Calcium-calmodulin protein kinase II (CaMKII) has been shown to be responsible for enhancing ionotropic glutamate receptor mediated activity. CaMKII also has been shown to be a molecular intermediate in both long-term potentiation (LTP) and peripherally induced central sensitization. After contusive SCI, the segments immediately rostral to the injury site show an increase in activated CaMKII. Application of CaMKII inhibitor, KN-93, during recording 35 days post injury, reduces spinal hyperexcitability induced by SCI. \r\n | en_US |
| dc.format.medium | electronic | en_US |
| dc.identifier.other | etd-12212005-164154 | en_US |
| dc.identifier.uri | http://hdl.handle.net/2152.3/298 | |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. | en_US |
| dc.subject | NBQX | en_US |
| dc.subject | KN-93 | en_US |
| dc.subject | D-AP5 | en_US |
| dc.title | The role of ionotropic glutamate receptors in chronic central pain after spinal cord injury | en_US |
| dc.type.genre | dissertation | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Neuroscience | en_US |
| thesis.degree.grantor | The University of Texas Medical Branch | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | PhD | en_US |