Objective To determine whether activation and/or inhibition of α-adrenoreceptors influences substance P （SP） release from dorsal root ganglion （DRG） primary sensory neurons in vitro. Methods DRGs were dissected from 15-day embryonic Wistar rats. DRG neurons were dissociated and cultured for 2 d and then exposed to noradrenaline （NA） alone （1×10-4 mol/L）, or along with the α1-adrenoreceptor antagonist prazosin （1×10-6 mol/L） or the α2-adrenoreceptor antago- nist yohimbine （1×10-5 mol/L） for 4 d. Then, RT-PCR was used to determine the levels of preprotachykinin （PPT） mRNA encoding for SP and Western blot to assess the protein levels of SP. Basal and capsaicin （CAP）-evoked SP release were measured by enzyme-linked immunosorbent assay （ELISA）. Results CAP-evoked SP release was sensitized by NA and this effect was inhibited by pre-incubation with prazosin but not with yohimbine. The levels of PPT mRNA, SP peptide, and basal SP release did not change significantly in any of the experimental conditions. Conclusion NA may significantly increase CAP-evoked SP release through activation of α-adrenoreceptors, which may contribute to noradrenergic pain modulation.
