NORADRENALINE ENHANCES ATP P2X3 RECEPTOR EXPRESSION IN DORSAL ROOT GANGLION NEURONS OF RATS

Increasing evidence indicates that both the ATP P2X receptors and adrenergic systems play a very important role in the development of nociception. However, there is little information concerning the interactions between these two systems in the dorsal root ganglia (DRG). In the present study, we examined the effects of noradrenaline (NA) on the P2X3 receptor expression in the DRG of Sprague-Dawley rats. The direct effect of NA on the P2X3 mRNA and protein expression was determined in cultured DRG neurons. Treatment of neuronal cultures with NA (50 nM, 5 h) induced a two-fold increase in P2X3 expression, as detected with real-time RT-PCR and Western blots, but had no effect on P2X2 expression. In electrophysiological experiments, perfusion of neuronal cultures with the P2X3 agonist (alpha beta-methylene ATP) increased neuronal firing rate by 139% and 273% in neurons treated with either PBS (control) or NA, respectively, indicating that chronic NA treatment significantly enhanced the neuronal response to P2X3 activation. In behavior studies, combination of NA (2 or 20 nmol) with alpha beta-methylene ATP (10 nmol) produced a significant and long lasting augmentation of thermal hyperalgesia. These results indicate that NA stimulates P2X3 expression in DRG neurons, and this could contribute to the development of pain sensitization. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.