Journal article
Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia
The Journal of clinical investigation, Vol.118(7), pp.2471-2481
07/01/2008
Handle:
https://hdl.handle.net/2376/106701
PMCID: PMC2423866
PMID: 18551194
Abstract
Stress-induced analgesia (SIA) is a key component of the defensive behavioral “fight-or-flight” response. Although the neural substrates of SIA are incompletely understood, previous studies have implicated the hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ (N/OFQ) peptidergic systems in the regulation of SIA. Using immunohistochemistry in brain tissue from wild-type mice, we identified N/OFQ-containing fibers forming synaptic contacts with Hcrt neurons at both the light and electron microscopic levels. Patch clamp recordings in GFP-tagged mouse Hcrt neurons revealed that N/OFQ hyperpolarized, decreased input resistance, and blocked the firing of action potentials in Hcrt neurons. N/OFQ postsynaptic effects were consistent with opening of a G protein–regulated inwardly rectifying K
+
(GIRK) channel. N/OFQ also modulated presynaptic release of GABA and glutamate onto Hcrt neurons in mouse hypothalamic slices.
Orexin/ataxin-3
mice, in which the Hcrt neurons degenerate, did not exhibit SIA, although analgesia was induced by i.c.v. administration of Hcrt-1. N/OFQ blocked SIA in wild-type mice, while coadministration of Hcrt-1 overcame N/OFQ inhibition of SIA. These results establish what is, to our knowledge, a novel interaction between the N/OFQ and Hcrt systems in which the corticotropin-releasing factor and N/OFQ systems coordinately modulate the Hcrt neurons to regulate SIA.
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Details
- Title
- Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia
- Creators
- Xinmin Xie - Biosciences Division, SRI International, Menlo Park, California, USAJonathan P Wisor - Biosciences Division, SRI International, Menlo Park, California, USAJunko Hara - Biosciences Division, SRI International, Menlo Park, California, USATara L Crowder - Biosciences Division, SRI International, Menlo Park, California, USARobin LeWinter - Biosciences Division, SRI International, Menlo Park, California, USATaline V Khroyan - Biosciences Division, SRI International, Menlo Park, California, USAAkihiro Yamanaka - Biosciences Division, SRI International, Menlo Park, California, USASabrina Diano - Biosciences Division, SRI International, Menlo Park, California, USATamas L Horvath - Biosciences Division, SRI International, Menlo Park, California, USATakeshi Sakurai - Biosciences Division, SRI International, Menlo Park, California, USALawrence Toll - Biosciences Division, SRI International, Menlo Park, California, USAThomas S Kilduff - Biosciences Division, SRI International, Menlo Park, California, USA
- Publication Details
- The Journal of clinical investigation, Vol.118(7), pp.2471-2481
- Academic Unit
- Biomedical Sciences, Department of
- Publisher
- American Society for Clinical Investigation
- Identifiers
- 99900546817301842
- Language
- English
- Resource Type
- Journal article