Chronic NGF treatment of rat nociceptive DRG neurons in culture facilitates desensitization and deactivation of GABAA receptor-mediated currents.

摘要

The present study tested the hypothesis that nerve growth factor (NGF) could affect presynaptic inhibition mediated by GABA(A) (GABA-sensitive ionotropic receptors) receptors on the afferents of nociceptive dorsal root ganglia (DRG) neurons, thus reducing the filtering of central nociceptive signals. To investigate this issue, small-diameter, nociceptive DRG neurons were cultured for 48-72 h either in the normal medium or in the presence of NGF (50 ng ml(-1)). After 15 min washout, cells were patch clamped with Cs(+) containing electrodes to block GABA(B) (GABA-sensitive metabotropic receptors) receptor-activated currents. Chronically treated DRG neurons showed no difference in the peak amplitude of GABA-induced currents. However, NGF-treated cells exhibited increased fading of the response to continuous GABA application, with faster desensitization onset, decreased residual current at the end of agonist application and slower recovery from desensitization. Moreover, the deactivation phase after brief agonist pulses was also accelerated. Unlike responses to GABA, chronic NGF treatment had no effect on the desensitization process to the excitatory transmitter ATP, as no difference in peak amplitude, fast and slow time constants of current decay was found. Experimental tests indicated that the observed effects on GABA currents were not a reactive process triggered by washing out NGF after its long application. Acutely applied NGF did not change GABA(A) receptor-mediated responses. NGF-treated neurons showed decreased sensitivity to the antagonist picrotoxin. The action of pentobarbitone, midazolam, bicuculline or gabazine was, however, unchanged. These observations suggest that the modulation of GABA(A) receptor function of DRG nociceptors by NGF may contribute to the algogenic action of this neurotrophin.British Journal of Pharmacology (2004) 142, 425-434. doi:10.1038/sj.bjp.0705813