Peripheral nerve injury induces trans-synaptic modification of channels, receptors and signal pathways in rat dorsal spinal cord.
Peripheral tissue injury-induced central sensitization may result from the altered biochemical properties of spinal dorsal horn. However, peripheral nerve injury-induced modification of genes in the dorsal horn remains largely unknown. Here we identified strong changes of 14 channels, 25 receptors and 42 signal transduction related molecules in Sprague-Dawley rat dorsal spinal cord 14 days after peripheral axotomy by cDNA microarray. Twenty-nine genes were further confirmed by semiquantitative RT-PCR, Northern blotting, in situ hybridization and immunohistochemistry. These regulated genes included Ca2+ channel alpha1E and alpha2/delta1 subunits, alpha subunits for Na+ channel 1 and 6, Na+ channel beta subunit, AMAP receptor GluR3 and 4, GABAA receptor alpha5 subunit, nicotinic acetylcholine receptor alpha5 and beta2 subunits, PKC alpha, betaI and delta isozymes, JNK1-3, ERK2-3, p38 MAPK and BatK and Lyn tyrosine-protein kinases, indicating that several signal transduction pathways were activated in dorsal spinal cord by peripheral nerve injury. These results demonstrate that peripheral nerve injury causes phenotypic changes in spinal dorsal horn. Increases in Ca2+ channel alpha2/delta1 subunit, GABAA receptor alpha5 subunit, Na+ channels and nicotinic acetylcholine receptors in both dorsal spinal cord and dorsal root ganglia indicate their potential roles in neuropathic pain control.
Laboratory of Sensory System, Institute of Neurosciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Liang
L
Yang
Fang-Xiong
FX
Zhang
Fen
F
Huang
Yin-Jing
YJ
Lu
Guo-Dong
GD
Li
Lan
L
Bao
Hua-Sheng
HS
Xiao
Xu
X
Zhang
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D007473:Ion Channels / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D007473:Ion Channels; D011956:Receptors, Cell Surface