@article{oai:kanazawa-u.repo.nii.ac.jp:00013295,
 author = {Xie, Xinmin and Wisor, Jonathan P. and Hara, Junko and Crowder, Tara L. and LeWinter, Robin and Khroyan, Taline V. and Yamanaka, Akihiro and Diano, Sabrina and Horvath, Takeshi L. and Sakurai, Takeshi and Toll, Lawrence and Kilduff, Thomas S.},
 issue = {7},
 journal = {Journal of Clinical Investigation},
 month = {Jul},
 note = {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., 金沢大学医薬保健研究域医学系},
 pages = {2471--2481},
 title = {Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia},
 volume = {118},
 year = {2008}
}