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

In spinal nerve ligated Lewis strain neuropathic rats, pain behaviors and t he rate of ectopic discharges of injured sensory neurons were significantly reduced by systemic injection of phentolamine. A pharmacological study ind icated that this adrenergic dependency was mediated by al-adrenoceptors (al pha (1)-AR). The development of adrenergic sensitivity in injured sensory n eurons might have resulted from changes in adrenoceptor expression as a con sequence of changed expression of adrenoceptor genes. This possibility was examined by determining the changes in the mRNA expression of 3 subtypes of alpha (1)-ARs, alpha (1a)-, alpha (1b)-, and alpha (1d)-ARs, in the dorsal root ganglia (DRG) after spinal nerve ligation. The L4 and L5 spinal nerve s were tightly ligated in Lewis rats. One week later, the L4 and L5 DRG wer e collected and RNase protection assay (RPA) and in situ hybridization were performed, In the DRG of unoperated rats, a moderate amount of alpha (1a)- AR mRNA was present while the amount of either alpha (1b)-AR or alpha (1d)- AR mRNA was small. After spinal nerve ligation, there was a significant inc rease in the amount of alpha (1b)-AR mRNA in the nerve ligated DRG as measu red by RPA. The amount of alpha (1a)-AR mRNA was decreased to 20% of the no rmal level while that of alpha (1d)-AR mRNA did not change. The in situ hyb ridization study showed that the number of alb-AR mRNA positive neurons inc reased in spinal nerve ligated DRG, confirming the results of RPA study. Th ese data suggest that the up-regulated expression of alpha (1b)-AR rnRNA in axotomized DRG neurons may play an important role in the development of ad renergic sensitivity in injured sensory neurons and thus contribute to the sympathetically maintained pain in spinal nerve ligated neuropathic Lewis r ats. (C) 2001 Elsevier Science B V All rights reserved.