Objective To investigate the regulatory effects of nerve growth factor (NGF) on basal and capsaicin-induced release of neuropeptide substance P (SP) in primary cultured embryonic rat dorsal root ganglion (DRG) neurons. Methods DRGs were dissected from 15-day-old embryonic Wistar rats. DRG neurons were dissociated and cultured, and then exposed to different concentrations of NGF (10 ng/mL, 30 ng/mL, or 100 ng/mL) for 72 h. The neurons cultured in media without NGF served as control. RT-PCR were used for detecting the mRNAs of SP and vanilloid receptor 1 (VR1) in the DRG neurons. The SP basal and capsaicin (100 nmol/L)-induced release in the culture were measured by radioimmunoassay (RIA). Results SP mRNA and VR1 mRNA expression increased in primary cultured DRG neurons in a dose-dependent manner of NGF. Both basal release and capsaicin-evoked release of SP increased in NGF-treated DRG neurons compared with in control group. The capsaicin-evoked release of SP also increased in a dose-dependent manner of NGF. Conclusion NGF may promote both basal release and capsaicin-evoked release of SP. NGF might increase the sensitivity of nociceptors by increasing the SP mRNA or VR1 mRNA.