Artemin–GFRα3 interactions partially contribute to acute inflammatory hypersensitivity

•Artemin antibodies block its binding to GFRα3 and inhibit pRet signalling.•Artemin-induced CGRP secretion from rat DRG cultures is reduced by monoclonal antibodies.•Delayed administration of anti-artemin antibodies partially reverse inflammatory hypersensitivity in mice. 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.