title: Artemin-GFRα3 interactions partially contribute to acute inflammatory hypersensitivity.
abstract: The expression of artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF) family ligand, increases in pre-clinical models of nociception and recent evidence suggests this growth factor may play a causative role in inflammatory pain mechanisms. The aim of this study was to demonstrate functional inhibition of ARTN with monoclonal antibodies and to determine whether ARTN neutralisation could reverse inflammatory pain in mice. We show that monoclonal antibodies with high affinity to ARTN, completely inhibit ARTN-induced Ret and ERK activation in a human neuroblastoma cell line, and block capsaicin-induced CGRP secretion from primary rat DRG cultures. In addition, administration of anti-ARTN antibodies to mice provides a transient, partial reversal (41%) of FCA-induced mechanical hypersensitivity. Anti-ARTN antibodies had no effect on hypersensitivity in response to partial nerve ligation in mice. These data suggest that ARTN-GFRα3 interactions partially mediate early stage nociceptive signalling following an inflammatory insult.
authors.affiliation: MedImmune, Granta Park, Cambridge CB21 6GH, UK. thorntonp@medimmune.com
authors.forename: Peter
authors.initials: P
authors.lastname: Thornton
authors.forename: Jon P
authors.initials: JP
authors.lastname: Hatcher
authors.forename: Ian
authors.initials: I
authors.lastname: Robinson
authors.forename: Becky
authors.initials: B
authors.lastname: Sargent
authors.forename: Bo
authors.initials: B
authors.lastname: Franzén
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martino
authors.forename: Lisa
authors.initials: L
authors.lastname: Kitching
authors.forename: Colin P
authors.initials: CP
authors.lastname: Glover
authors.forename: Dina
authors.initials: D
authors.lastname: Anderson
authors.forename: Heidi
authors.initials: H
authors.lastname: Forsmo-Bruce
authors.forename: Choon Pei
authors.initials: CP
authors.lastname: Low
authors.forename: Fiona
authors.initials: F
authors.lastname: Cusdin
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Dosanjh
authors.forename: Wendy
authors.initials: W
authors.lastname: Williams
authors.forename: Ann-Charlott
authors.initials: AC
authors.lastname: Steffen
authors.forename: Simon
authors.initials: S
authors.lastname: Thompson
authors.forename: Malin
authors.initials: M
authors.lastname: Eklund
authors.forename: Chris
authors.initials: C
authors.lastname: Lloyd
authors.forename: Iain
authors.initials: I
authors.lastname: Chessell
authors.forename: Jane
authors.initials: J
authors.lastname: Hughes
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: C490887:Artn protein, rat; C494995:Gfra3 protein, rat; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009419:Nerve Tissue Proteins