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The p75 receptor is associated with inflammatory thermal hypersensitivity
Author(s) -
Watanabe Tomoko,
Ito Toshinori,
Inoue Gen,
Ohtori Seiji,
Kitajo Keiko,
Doya Hideo,
Takahashi Kazuhisa,
Yamashita Toshihide
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21808
Subject(s) - nerve growth factor , hyperalgesia , inflammation , medicine , receptor , pharmacology , nociception , tropomyosin receptor kinase a , calcitonin gene related peptide , neurotrophin , immunology , neuropeptide
Inflammatory pain, characterized by a decrease in the nociceptive threshold, arises through the actions of inflammatory mediators, and one of the key molecules is nerve growth factor (NGF). Here we report that the administration of neutralizing antibody to the neurotrophin receptor p75 (p75 NTR ) blocks hyperalgesia, which develops with complete Freund's adjuvant (CFA)‐induced inflammation or with an intraplantar injection of NGF. Although CFA injection results in the up‐regulation of calcitonin gene‐related peptide (CGRP) levels in the primary sensory neurons, blocking p75 NTR abolishes this effect. We further demonstrate that pro‐NGF is the predominant ligand of p75 NTR in vivo. Plasmin treatment, which is intended to decompose pro‐NGF, ameliorates CFA‐induced hyperalgesia. In addition, an intraplantar injection of pro‐NGF induces hyperalgesia. These data together suggest that pro‐NGF, as well as mature NGF, binding to p75 NTR plays an important role in inflammation‐induced hyperalgesia. Interference in the binding may provide a therapeutic approach for the treatment of inflammatory pain. © 2008 Wiley‐Liss, Inc.