title: Oxytocin receptor: Expression in the trigeminal nociceptive system and potential role in the treatment of headache disorders.
abstract: OBJECTIVE
  Our studies investigated the location of oxytocin receptors in the peripheral trigeminal sensory system and determined their role in trigeminal pain.
  
  
  METHODS
  Oxytocin receptor expression and co-localization with calcitonin gene-related peptide was investigated in rat trigeminal ganglion using immunohistochemistry. Enzyme-linked immunosorbent assay was used to determine the effects of facial electrocutaneous stimulation and adjuvant-induced inflammation of the temporomandibular joint on oxytocin receptor expression in the trigeminal ganglion. Finally, the effects of oxytocin on capsaicin-induced calcitonin gene-related peptide release from dural nociceptors were investigated using isolated rat dura mater.
  
  
  RESULTS
  Oxytocin receptor immunoreactivity was present in rat trigeminal neurons. The vast majority of oxytocin receptor immunoreactive neurons co-expressed calcitonin gene-related peptide. Both electrocutaneous stimulation and adjuvant-induced inflammation led to a rapid upregulation of oxytocin receptor protein expression in trigeminal ganglion neurons. Oxytocin significantly and dose-dependently decreased capsaicin-induced calcitonin gene-related peptide release from dural nociceptors.
  
  
  CONCLUSIONS
  Oxytocin receptor expression in calcitonin gene-related peptide containing trigeminal ganglion neurons, and the blockade of calcitonin gene-related peptide release from trigeminal dural afferents suggests that activation of these receptors may provide therapeutic benefit in patients with migraine and other primary headache disorders.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tzabazis
authors.affiliation: Trigemina, Inc., Moraga, CA, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Mechanic
authors.affiliation: Trigemina, Inc., Moraga, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Miller
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Klukinov
authors.affiliation: Trigemina, Inc., Moraga, CA, USA.
authors.forename: Conrado
authors.initials: C
authors.lastname: Pascual
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Manering
authors.affiliation: Trigemina, Inc., Moraga, CA, USA Department of Psychiatry, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Dean S
authors.initials: DS
authors.lastname: Carson
authors.affiliation: Trigemina, Inc., Moraga, CA, USA.
authors.forename: Allon
authors.initials: A
authors.lastname: Jacobs
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Cuellar
authors.affiliation: HealthPartners Center for Memory and Aging, Regions Hospital, St. Paul, MN, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Frey
authors.affiliation: Trigemina, Inc., Moraga, CA, USA Department of Plastic Surgery, Kaiser Permanente Medical Center, San Jose, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jacobs
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA Trigemina, Inc., Moraga, CA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Angst
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, USA Trigemina, Inc., Moraga, CA, USA dcyeomans@stanford.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D020773:Headache Disorders / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009619:Nociceptors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome; D012668:Trigeminal Ganglion / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018045:Receptors, Oxytocin; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; Oxytocin; headache; inflammation; pain; trigeminal