title: Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.
abstract: BACKGROUND
  Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine.
  
  
  METHODS
  NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model.
  
  
  RESULTS
  Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6).
  
  
  CONCLUSIONS
  These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine.
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA.
authors.forename: Dipti
authors.initials: D
authors.lastname: Tillu
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Asiedu
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Weinstein
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA.
authors.forename: Ohannes
authors.initials: O
authors.lastname: Melemedjian
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA.
authors.forename: Theodore
authors.initials: T
authors.lastname: Price
authors.affiliation: Department of Pharmacology, The University of Arizona College of Medicine, USA School of Behavioral and Brain Sciences, The University of Texas at Dallas, USA gregory.dussor1@utdallas.edu.
authors.forename: Gregory
authors.initials: G
authors.lastname: Dussor
mesh_terms: D000344:Afferent Pathways; D000818:Animals; D001522:Behavior, Animal; D004388:Dura Mater / Q000378:metabolism* / Q000473:pathology*; D005347:Fibroblasts; D006261:Headache / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008578:Meninges / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000473:pathology
chemical_list: D009638:Norepinephrine
keywords: Migraine; dura mater; fibroblast; headache; norepinephrine; stress