The p75 receptor is associated with inflammatory thermal hypersensitivity.
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.
Watanabe
Tomoko
T
Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ito
Toshinori
T
Inoue
Gen
G
Ohtori
Seiji
S
Kitajo
Keiko
K
Doya
Hideo
H
Takahashi
Kazuhisa
K
Yamashita
Toshihide
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D018836:Inflammation Mediators; D008024:Ligands; D020800:Receptor, Nerve Growth Factor; D005620:Freund's Adjuvant; D020932:Nerve Growth Factor; D005341:Fibrinolysin; D015740:Calcitonin Gene-Related Peptide