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Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia
- Source :
- Journal of Clinical Investigation.
- Publication Year :
- 2008
- Publisher :
- American Society for Clinical Investigation, 2008.
-
Abstract
- 金沢大学医薬保健研究域医学系<br />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.
- Subjects :
- Male
Pain Threshold
Cytoplasm
medicine.medical_specialty
Hypothalamus, Posterior
Narcotic Antagonists
Presynaptic Terminals
Neuropeptide
Mice, Transgenic
Tetrodotoxin
Nociceptin Receptor
Membrane Potentials
Mice
Stress, Physiological
Postsynaptic potential
Internal medicine
Reaction Time
medicine
Animals
G protein-coupled inwardly-rectifying potassium channel
Patch clamp
Ataxin-3
Opioid peptide
Neurons
Orexins
Behavior, Animal
Chemistry
Neuropeptides
Intracellular Signaling Peptides and Proteins
Glutamate receptor
Brain
Nuclear Proteins
General Medicine
Immunohistochemistry
Orexin
Electrophysiology
Mice, Inbred C57BL
Nociceptin receptor
Endocrinology
Opioid Peptides
nervous system
Receptors, Opioid
Calcium
Female
Analgesia
Neuroscience
Research Article
Transcription Factors
Subjects
Details
- ISSN :
- 00219738
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....1c54149037dd596e7ef567b305999be1