Up-Regulation of Anterior Cingulate Cortex NR2B Receptors Contributes to Visceral Pain Responses in Rats

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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Author(s)

  • Jing Fan
  • Xiaoyin Wu
  • Zhijun Cao
  • Shengliang Chen
  • Chung Owyang

Detail(s)

Original languageEnglish
Journal / PublicationGastroenterology
Volume136
Issue number5
Publication statusPublished - May 2009
Externally publishedYes

Abstract

Background & Aims: Electrophysiologic and behavioral studies have shown that increased N-methyl-D-aspartate (NMDA)-receptor activation of anterior cingulate cortex (ACC) neurons has a critical role in modulating visceral pain responses in viscerally hypersensitive (VH) rats. This study aimed to identify the NMDA receptor subtypes in perigenual ACC (pACC) neurons involved in the facilitation of visceral nociception. Methods: We performed in vivo electrophysiologic recordings of pACC neurons and examined the visceromotor response (VMR) to colorectal distention (CRD) in normal and VH rats induced by colonic anaphylaxis. The NR2A-subtype-receptor antagonist [(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid (NVP-AAM077) and the NR2B-receptor-antagonist Ro25-6981 were microinjected into the pACC. To down-regulate NR2B-receptor gene expression, an NR2B-specific small interfering RNA (siRNA) and a plasmid (pEGFP-N1) that expressed the green fluorescent protein were administered into ACC neurons by electroporation. Results: Reverse microdialysis of NVP-AAM077 had no effect on basal and CRD-induced ACC neuronal firing in VH and control groups. In VH rats, Ro25-6981 (500 μmol/L) inhibited ACC neuronal firing, evoked by 30 and 50 mm Hg CRD, by 98% and 52%, respectively. NVP-AAM077 did not affect the VMR in either group. Ro25-6981 significantly suppressed the VMR in VH but not normal rats. Immunoblot analysis showed increased NR2B-receptor expression in the pACC of VH rats. NR2B siRNA-treated VH rats showed a significant reduction in the VMR, compared with controls. Conclusions: The NR2B subunit of the NMDA receptor has a critical role in the modulation of ACC sensitization and visceral pain responses in VH rats. © 2009 AGA Institute.

Citation Format(s)

Up-Regulation of Anterior Cingulate Cortex NR2B Receptors Contributes to Visceral Pain Responses in Rats. / Fan, Jing; Wu, Xiaoyin; Cao, Zhijun; Chen, Shengliang; Owyang, Chung; Li, Ying.

In: Gastroenterology, Vol. 136, No. 5, 05.2009.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review