Transcriptional profiling of spinal cord injury-induced central neuropathic pain.
Central neuropathic pain (CNP) is an important problem following spinal cord injury (SCI), because it severely affects the quality of life of SCI patients. As in the patient population, the majority of rats develop significant allodynia (CNP rats) after moderate SCI. However, about 10% of SCI rats do not develop allodynia, or develop significantly less allodynia than CNP rats (non-CNP rats). To identify transcriptional changes underlying CNP development after SCI, we used Affymetrix DNA microarrays and RNAs extracted from the spinal cords of CNP and non-CNP rats. DNA microarry analysis showed significantly increased expression of a number of genes associated with inflammation and astrocytic activation in the spinal cords of rats that developed CNP. For example, mRNA levels of glial fibrilary acidic protein (GFAP) and Aquaporin 4 (AQP4) significantly increased in CNP rats. We also found that GFAP, S100beta and AQP4 protein elevation persisted for at least 9 months throughout contused spinal cords, consistent with the chronic nature of CNP. Thus, we hypothesize that CNP development results, in part, from dysfunctional, chronically "over-activated" astrocytes. Although, it has been shown that activated astrocytes are associated with peripheral neuropathic pain, this has not previously been demonstrated in CNP after SCI.
Nesic
Olivera
O
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555-1072, USA.
Lee
Julieann
J
Johnson
Kathia M
KM
Ye
Zaiming
Z
Xu
Guo-Ying
GY
Unabia
Geda C
GC
Wood
Thomas G
TG
McAdoo
David J
DJ
Westlund
Karin N
KN
Hulsebosch
Claire E
CE
Regino Perez-Polo
J
J
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D009414:Nerve Growth Factors / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation / Q000502:physiology*
D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins