Differential expression of alpha1-adrenoceptor subtype mRNAs in the dorsal root ganglion after spinal nerve ligation

Abstract

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 α 1-adrenoceptors (α 1-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 α 1-ARs, α 1a-, α 1b-, and α 1d-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 α 1a-AR mRNA was present while the amount of either α 1b-AR or α 1d-AR mRNA was small. After spinal nerve ligation, there was a significant increase in the amount of α 1b-AR mRNA in the nerve ligated DRG as measured by RPA. The amount of α 1a-AR mRNA was decreased to 20% of the normal level while that of α 1d-AR mRNA did not change. The in situ hybridization study showed that the number of α 1b-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 α 1b-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.