Low affinity NGF receptor (p75 neurotrophin receptor) inhibitory antibody reduces pain behavior and CGRP expression in DRG in the mouse sciatic nerve crush model.
Nerve growth factor (NGF) and its low-affinity receptor, p75 neurotrophin receptor (p75 NTR), are important mediators of pain. To explore further the mechanisms involved, we examined suppression of pain behavior and expression of neuropeptides such as calcitonin gene-related peptide (CGRP) using a p75 NTR inhibitory antibody, in a mouse sciatic nerve crush model. In the nerve-injured model, 150 microg of a p75 NTR inhibitory antibody or 10 microl of saline were applied. The sciatic nerve in the sham-operated group was uninjured. Mechanical allodynia was measured for 2 weeks. CGRP and p75 NTR expression in L5 dorsal root ganglions (DRGs) was examined immunohistochemically. Mechanical allodynia was found in the two nerve injured groups, but not in the sham-operated group (p < 0.05). However, the magnitude of the mechanical allodynia was significantly decreased after application of p75 NTR inhibitory antibody (p < 0.05). CGRP and p75 NTR immunoreactivity in the L5 DRG neurons was upregulated in the injured nerve groups compared with the sham-operated group; however, p75 NTR inhibitory antibody decreased the CGRP and p75 NTR expression (p < 0.01). Application of the p75 NTR inhibitory antibody to the pinched sciatic nerve suppressed CGRP and p75 NTR expression and pain behavior.
Fukui
Yu
Y
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Ohtori
Seiji
S
Yamashita
Masaomi
M
Yamauchi
Kazuyo
K
Inoue
Gen
G
Suzuki
Munetaka
M
Orita
Sumihisa
S
Eguchi
Yawara
Y
Ochiai
Nobuyasu
N
Kishida
Shunji
S
Takaso
Masashi
M
Wakai
Ken
K
Hayashi
Yasushi
Y
Aoki
Yasuchika
Y
Takahashi
Kazuhisa
K
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors*; D005727:Ganglia, Spinal / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009409:Nerve Crush; D010146:Pain / Q000523:psychology*; D017288:Pain Threshold; D020800:Receptor, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D014110:Touch
D000906:Antibodies; D020800:Receptor, Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide