Potentiation of Excitatory Transmission in Substantia Gelatinosa Neurons of Rat Spinal Cord by Inhibition of Estrogen Receptor Alpha

Yan-Qing Zhong,Kai-Cheng Li,Xu Zhang

doi:10.1186/1744-8069-6-92

Yan-Qing Zhong, Kai-Cheng Li + Show 1 more

Open Access

https://doi.org/10.1186/1744-8069-6-92

Copy DOI

Abstract

BackgroundIt has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission. One of the estrogen receptor (ER) subtypes, estrogen receptor alpha (ERα), is expressed in the spinal laminae I-V, including substantia gelatinosa (SG, lamina II). However, it is unclear how ERs are involved in the modulation of nociceptive transmission.ResultsIn the present study, a selective ERα antagonist, methyl-piperidino-pyrazole (MPP), was used to test the potential functional roles of spinal ERα in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of MPP on SG neurons in the dorsal root-attached spinal cord slice prepared from adult rats. We found that MPP increased glutamatergic excitatory postsynaptic currents (EPSCs) evoked by the stimulation of either Aδ- or C-afferent fibers. Further studies showed that MPP treatment dose-dependently increased spontaneous EPSCs frequency in SG neurons, while not affecting the amplitude. In addition, the PKC was involved in the MPP-induced enhancement of synaptic transmission.ConclusionsThese results suggest that the selective ERα antagonist MPP pre-synaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive transmission evoked by Aδ- and C-fiber stimulation could be potentiated by blocking ERα in the spinal neurons. Thus, the spinal estrogen may negatively regulate the nociceptive transmission through the activation of ERα.

Highlights

It has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission
We found that superfusion of MPP (10 μM) resulted in a reversible enhancement in spontaneous EPSC (sEPSC) frequency (Figure 2A and 2B; 234 ± 9% of control at 3 min following its application, n = 8; P < 0.001)
We found that the frequency of sEPSC was reduced by bath-applied 17bestradiol (1 μM), and this effect could be reversed by MPP (Figure 3A, n = 6)

Summary

Introduction

It has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission. Estrogen may modulate nociceptive responses through the increase of glutamateinduced currents, the inhibition of g-aminobutyric acid (GABA) and glycine (Gly) receptors, or the modulation of the opioid receptors in the spinal dorsal horn [9,10,11]. Considering that the superficial dorsal horn of the spinal cord, especially substantia gelatinosa (SG, lamina II), plays an important role in the modulation of synaptic transmission of fine myelinated A (Aδ)- and unmyelinated C-afferent fibers [21,22], we used a selective ERa antagonist, methylpiperidino-pyrazole (MPP) [23], to examine the function of spinal ERa in nociceptive transmission in SG neurons.

Results

Conclusion