Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: relation to central neuropathic pain.
Spinal cord injury (SCI) often leads to the generation of chronic intractable neuropathic pain. The mechanisms that lead to chronic central neuropathic pain (CNP) following SCI are not well understood, resulting in ineffective treatments for pain relief. Studies have demonstrated persistent hyperexcitability of dorsal horn neurons which may provide a substrate for CNP. We propose a number of similarities between CNP mechanisms and mechanisms that occur in long-term potentiation, in which hippocampal neurons are hyperexcitable. One biochemical similarity may be activation of the transcription factor, cyclic AMP response element-binding protein (CREB), via phosphorylation (pCREB). The current study was designed to examine whether tactile allodynia that develops in segments rostral to SCI (at-level pain) correlates with an increase in CREB phosphorylation in specific neurons known to be involved in allodynia, the spinothalamic tract (STT) cells. This study determined that, in animals experiencing at-level allodynia 35 days after SCI, pCREB was upregulated in the spinal cord segment rostral to the injury. In addition, pCREB was found to be upregulated specifically in STT cells in the rostral segment 35 days after SCI. These findings suggest one mechanism of maintained central neuropathic pain following SCI involves persistent upregulation of pCREB expression within STT cells.
Crown
E D
ED
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Blvd, Route 1043, Galveston, TX 77555-1043, USA.
Ye
Z
Z
Johnson
K M
KM
Xu
G-Y
GY
McAdoo
D J
DJ
Westlund
K N
KN
Hulsebosch
C E
CE
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D013133:Spinothalamic Tracts / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013266:Stilbamidines / Q000378:metabolism; D015854:Up-Regulation
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D017362:Cyclic AMP Response Element-Binding Protein; D013266:Stilbamidines