Nocistatin and nociceptin exert opposite effects on the excitability of central amygdala nucleus-periaqueductal gray projection neurons

Ying Ling Chen, Allen H. Li, Tu Hsueh Yeh, An Hsun Chou, Hung Li Wang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

26 Scopus citations

Abstract

Central amygdala nucleus (CeA)-periaqueductal gray (PAG) pathway is the component of descending antinociceptive circuitry. Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) produce supraspinal pronociceptive and antinociceptive effects, respectively. We hypothesized that opposite effects of N/OFQ and NST on supraspinal pain modulation result from their opposing effects on the excitability of CeA-PAG projection neurons. This hypothesis was tested by investigating electrophysiological effects of N/OFQ and NST on medial CeA neurons that project to PAG (CeAM-PAG). N/OFQ hyperpolarized CeAM-PAG projection neurons by enhancing inwardly rectifying potassium conductance. In contrast, NST depolarized CeAM-PAG neurons by causing the opening of TRPC cation channels via Gαq/11-PLC-PKC pathway. CeAM-PAG neurons hyperpolarized by N/OFQ express CRF or neurotensin mRNA. NST-responsive CeAM-PAG neurons contain CRF or substance P mRNA. Our study provides the evidence that the molecular and cellular basis for opposite effects of N/OFQ and NST on supraspinal pain regulation is their opposing effects on the excitability of peptidergic CeAM-PAG neurons.

Original languageEnglish
Pages (from-to)76-88
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume40
Issue number1
DOIs
StatePublished - 05 01 2009

Keywords

  • CeA-PAG projection neurons
  • Central amygdala nucleus
  • Nociceptin/orphanin FQ
  • Nocistatin
  • Periaqueductal gray

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