• Peter Thornton, Jon P Hatcher, Ian Robinson, Becky Sargent, Bo Franzén, Giovanni Martino, Lisa Kitching, Colin P Glover, Dina Anderson, Heidi Forsmo-Bruce, Choon Pei Low, Fiona Cusdin, Bhupinder Dosanjh, Wendy Williams, Ann-Charlott Steffen, Simon Thompson, Malin Eklund, Chris Lloyd, Iain Chessell, and Jane Hughes.
• MedImmune, Granta Park, Cambridge CB21 6GH, UK. thorntonp@medimmune.com
• Neurosci. Lett. 2013 Jun 17;545:23-8.

AbstractThe 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.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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