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.
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Cellular and Molecular Neuroscience
Chen, Y. L., Li, A. H. L., Yeh, T. H., Chou, A. H., & Wang, H. L. (2009). Nocistatin and nociceptin exert opposite effects on the excitability of central amygdala nucleus-periaqueductal gray projection neurons. Molecular and Cellular Neuroscience, 40(1), 76-88. https://doi.org/10.1016/j.mcn.2008.09.003