Nerve growth factor augments neuronal responsiveness to noradrenaline in cultured dorsal root ganglion neurons of rats

Abstract

Increasing evidence indicates that both the nerve growth factor (NGF) and adrenergic systems play a very important role in the development of nociception. However, there is little information concerning the functional interactions between these two systems in the dorsal root ganglion (DRG). The present study tested the hypothesis that NGF could affect neuronal responsiveness to noradrenaline (NA) on the nociceptive DRG neurons, thus enhancing the nociceptive signals. To investigate this issue, spontaneous action potentials were recorded in cultured DRG neurons using current-clamp recording. When NGF (50 ng/ml, 24 h) was administered in the neuronal cultures, the neuronal firing response to NA (10 μM) was augmented in TrkA-positive neurons (3.02±0.28 Hz with NGF treatment vs. 1.36±0.14 Hz in control, P<0.05), indicating that chronic NGF treatment significantly enhanced the neuronal response to NA. Pretreatment of neurons with either the α-adrenergic receptor (AR) antagonist phentolamine (100 μM) or α1-AR antagonist prazosin (50 μM) significantly inhibited the enhanced firings of DRG neurons induced by NA. In addition, treatment of neuronal cultures with NGF (50 ng/ml, 24 h) induced a two-fold increase in α1b-AR expression, as detected with real-time reverse transcription PCR (RT-PCR) and Western blots, but had no effect on α2-AR expression. These observations indicate that NGF augmented neuronal responsiveness to NA in DRG neurons via increasing α1b-AR expression, and this could contribute to the development of pain sensitization.