Screening of differentially expressed genes in the hypothalamus of a rat neuropathic pain model following sciatic nerve injury.
BACKGROUND
Neuropathic pain is induced by injury or disease of the nervous system. Most studies have so far focused only on a few known molecules and signaling pathways among neurons. However, all signal transmissions involved in neuropathic pain appear to be an integral system at different molecular levels. This study was designed to screen the differentially expressed genes of the hypothalamus in chronic constriction injury (CCI) rats and analyze their functions in developing neuropathic pain.


METHODS
Ten adult female Sprague-Dawley rats ((200 +/- 10) g) were used in experimental group and sham group (n = 5 in each group). Mechanical allodynia tests were performed to ensure that the CCI rat model was constructed successfully. Total hypothalamus RNAs were isolated from each group. Forward suppression subtractive hybridization (SSH) library of rat hypothalamus was constructed and up-regulated cDNA clones at neuropathic pain states were obtained via suppressed subtractive hybridization technique and the functions of these genes were analyzed bioinformatically.


RESULTS
Mechanical allodynia tests showed that the experimental rats had a significantly reduced mechanical allodynia threshold 3 to 13 days after CCI vs sham surgery rats (P < 0.01), indicating that the model was successful. Forward SSH library of the rat hypothalamus was constructed successfully and 26 over-expressed expression sequence tags (ESTs) were obtained from these up-regulated cDNA clones.


CONCLUSIONS
Twenty-six up-regulated genes, involved in the regulation of cell cycle and apoptosis, signal transduction, and neuroprotection, may play key roles in decreasing mechanical withdraw thresholds in CCI rats, which implicates a multidimensional and integrated molecular mechanism at gene level in developing neuropathic pain with the supraspinal contributions.
Tang
Yi
Y
Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Chu
Guang-yue
GY
He
Hong-xuan
HX
Yu
Cui-ping
CP
An
Jian-xiong
JX
Guo
Xiang-yang
XY
D000818:Animals; D019295:Computational Biology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D007031:Hypothalamus / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D009693:Nucleic Acid Hybridization; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism*
D009569:Nitric Oxide