Oxytocin-induced membrane hyperpolarization in pain-sensitive dorsal root ganglia neurons mediated by Ca2+/nNOS/NO/KATP pathway Academic Article uri icon

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abstract

  • Oxytocin (OT) plays an important role in pain modulation and antinociception in the central nervous system. However, little is known about its peripheral effects. This study was conducted to investigate the effect of OT on the electrical properties of neurons in the dorsal root ganglia (DRG) and the underlying mechanisms. DRG neurons from adult rats were acutely dissociated and cultured. Intracellular Ca(2+) was determined by fluorescent microscopy using an indicator dye. The electrical properties of DRG neurons were tested by patch-clamp recording. The oxytocin receptor (OTR) and neuronal nitric oxide synthase (nNOS) on DRG neurons were assessed with immunofluorescence assays. OTR co-localized with nNOS in most of Isolectin B4 (IB4)-binding cultured DRG neurons in rats. OT decreased the excitability, increased the outward current, and evoked the membrane hyperpolarization in cultured DRG neurons. Sodium nitroprusside (SNP), the donor of nitric oxide (NO), exerted similar effects as OT on the membrane potential of cultured DRG neurons. OT increased the production of NO in DRGs and cultured DRG neurons. Pre-treatment of the OTR antagonist atosiban or the selective nNOS inhibitor N-Propyl-l-arginine (NPLA) significantly attenuated the hyperpolarization effect evoked by OT. OT produced a concentration-dependent increase in intracellular Ca(2+) in DRG neurons that responds to capsaicin, which can be attenuated by atosiban, but not by NPLA. OT-evoked membrane hyperpolarization and increase of outward current were distinctly attenuated by glibenclamide, a blocker of ATP-sensitive K(+) (KATP) channel. OT might be an endogenous antinociceptive agent and the peripheral antinociceptive effects of OT are mediated by activation of the Ca(2+)/nNOS/NO/KATP pathway in DRG neurons.

authors

  • Gong, L
  • Gao, F
  • Li, J
  • Li, J
  • Yu, X
  • Ma, X
  • Zheng, W
  • Cui, S
  • Liu, K
  • Zhang, M
  • Kunze, Wolfgang
  • Liu, CY

publication date

  • March 2015