TY - JOUR
T1 - Differential expression of alpha1-adrenoceptor subtype mRNAs in the dorsal root ganglion after spinal nerve ligation
AU - Xie, Jiangang
AU - Ho Lee, Young
AU - Wang, Chen
AU - Mo Chung, Jin
AU - Chung, Kyungsoon
N1 - Funding Information:
This work was supported by NIH grants NS35057, NS31680 and NS11255.
PY - 2001/9/30
Y1 - 2001/9/30
N2 - In spinal nerve ligated Lewis strain neuropathic rats, pain behaviors and the rate of ectopic discharges of injured sensory neurons were significantly reduced by systemic injection of phentolamine. A pharmacological study indicated that this adrenergic dependency was mediated by α1-adrenoceptors (α1-AR). The development of adrenergic sensitivity in injured sensory neurons might have resulted from changes in adrenoceptor expression as a consequence of changed expression of adrenoceptor genes. This possibility was examined by determining the changes in the mRNA expression of 3 subtypes of α1-ARs, α1a-, α1b-, and α1d-ARs, in the dorsal root ganglia (DRG) after spinal nerve ligation. The L4 and L5 spinal nerves were tightly ligated in Lewis rats. One week later, the L4 and L5 DRG were collected and RNase protection assay (RPA) and in situ hybridization were performed. In the DRG of unoperated rats, a moderate amount of α1a-AR mRNA was present while the amount of either α1b-AR or α1d-AR mRNA was small. After spinal nerve ligation, there was a significant increase in the amount of α1b-AR mRNA in the nerve ligated DRG as measured by RPA. The amount of α1a-AR mRNA was decreased to 20% of the normal level while that of α1d-AR mRNA did not change. The in situ hybridization study showed that the number of α1b-AR mRNA positive neurons increased in spinal nerve ligated DRG, confirming the results of RPA study. These data suggest that the up-regulated expression of α1b-AR mRNA in axotomized DRG neurons may play an important role in the development of adrenergic sensitivity in injured sensory neurons and thus contribute to the sympathetically maintained pain in spinal nerve ligated neuropathic Lewis rats.
AB - In spinal nerve ligated Lewis strain neuropathic rats, pain behaviors and the rate of ectopic discharges of injured sensory neurons were significantly reduced by systemic injection of phentolamine. A pharmacological study indicated that this adrenergic dependency was mediated by α1-adrenoceptors (α1-AR). The development of adrenergic sensitivity in injured sensory neurons might have resulted from changes in adrenoceptor expression as a consequence of changed expression of adrenoceptor genes. This possibility was examined by determining the changes in the mRNA expression of 3 subtypes of α1-ARs, α1a-, α1b-, and α1d-ARs, in the dorsal root ganglia (DRG) after spinal nerve ligation. The L4 and L5 spinal nerves were tightly ligated in Lewis rats. One week later, the L4 and L5 DRG were collected and RNase protection assay (RPA) and in situ hybridization were performed. In the DRG of unoperated rats, a moderate amount of α1a-AR mRNA was present while the amount of either α1b-AR or α1d-AR mRNA was small. After spinal nerve ligation, there was a significant increase in the amount of α1b-AR mRNA in the nerve ligated DRG as measured by RPA. The amount of α1a-AR mRNA was decreased to 20% of the normal level while that of α1d-AR mRNA did not change. The in situ hybridization study showed that the number of α1b-AR mRNA positive neurons increased in spinal nerve ligated DRG, confirming the results of RPA study. These data suggest that the up-regulated expression of α1b-AR mRNA in axotomized DRG neurons may play an important role in the development of adrenergic sensitivity in injured sensory neurons and thus contribute to the sympathetically maintained pain in spinal nerve ligated neuropathic Lewis rats.
KW - Axotomized sensory neuron
KW - In situ hybridization
KW - Lewis strain of rats
KW - Neuropathic pain
KW - RNase protection assay
KW - Sympathetically maintained pain
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U2 - 10.1016/S0169-328X(01)00201-7
DO - 10.1016/S0169-328X(01)00201-7
M3 - Article
C2 - 11589993
AN - SCOPUS:0035975650
SN - 0169-328X
VL - 93
SP - 164
EP - 172
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 2
ER -