title: Nociceptin/orphanin FQ modulates cortical activity and trigeminal nociception.
abstract: BACKGROUND
  Alterations in the levels of nociceptin/orphanin FQ (N/OFQ) have been reported in patients with primary headaches, including migraines and cluster headaches. These clinical observations suggest that N/OFQ is involved in the pathogenesis of primary headaches.
  
  
  OBJECTIVE
  The present study was conducted to determine the role of N/OFQ in the control of trigeminal nociception and cortical excitation.
  
  
  METHODS
  Cortical spreading depression (CSD) was elicited in Wistar rats by cortical application of potassium chloride, and electrocorticograms were recorded. N/OFQ was administered via an intracisternal injection. The presence of CSD-evoked trigeminal nociception was determined with Fos and transient receptor potential vanilloid 1 (TRPV1) immunoreactivity.
  
  
  RESULTS
  Nociceptin/orphanin FQ produced a biphasic effect on CSD generation, characterized by an initial attenuation followed by delayed potentiation. The amplitude of CSD waves were lower in the initial period but increased in the later period. The total number of CSD waves recorded in 1 hour was greater in the N/OFQ-treated group. Exposure to N/OFQ significantly increased the number of Fos-immunoreactive cells in the trigeminal nucleus caudalis and the number of TRPV1-immunoreactive cells in the trigeminal ganglia, indicating the enhancement of trigeminal nociception.
  
  
  CONCLUSIONS
  These results indicate that N/OFQ can lead to biphasic effect characterized by an initial inhibition, and delay potentiation that eventually intensify CSD-evoked trigeminal nociception.
authors.affiliation: Department of Physiology, Faculty of Medicine, Chulalongkorn University, Patumwan, Bangkok, Thailand.
authors.forename: Saknan
authors.initials: S
authors.lastname: Bongsebandhu-Phubhakdi
authors.forename: Thas
authors.initials: T
authors.lastname: Phisonkulkasem
authors.forename: Anan
authors.initials: A
authors.lastname: Srikiatkhachorn
mesh_terms: D000818:Animals; D019540:Area Under Curve; D013181:Cortical Spreading Depression / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D059225:Nociception / Q000502:physiology*; D018847:Opioid Peptides / Q000627:therapeutic use*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000378:metabolism; D014276:Trigeminal Nerve / Q000503:physiopathology*; D014277:Trigeminal Neuralgia; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D016760:Proto-Oncogene Proteins c-fos; D011957:Receptors, Opioid; D050916:TRPV Cation Channels; D000097629:Nociceptin; C493922:Trpv1 protein, rat