title: Potentiation of excitatory transmission in substantia gelatinosa neurons of rat spinal cord by inhibition of estrogen receptor alpha.
abstract: BACKGROUND
  It 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Zhong
authors.forename: Kai-Cheng
authors.initials: KC
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009413:Nerve Fibers, Myelinated; D036421:Nerve Fibers, Unmyelinated; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000502:physiology; D013376:Substantia Gelatinosa / Q000166:cytology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: C524478:1,3-bis(4-hydroxyphenyl)-4-methyl-5-(4-(2-piperidinylethoxy)phenol)-1H-pyrazole; D047628:Estrogen Receptor alpha; D010880:Piperidines; D011720:Pyrazoles