Inhibiting nerve growth factor or its receptors downregulates calcitonin gene-related peptide expression in rat lumbar dorsal root ganglia innervating injured intervertebral discs.
Nerve growth factor (NGF) and its dual structurally unrelated receptors, tropomyosin-related kinase A (TrkA) or p75 neurotrophin receptor (p75(NTR)), cause the pathogenesis of discogenic pain. To investigate the sensory innervation of injured rat lumbar intervertebral disc (IVD), we examined the expression of neuropeptides such as calcitonin gene-related peptide (CGRP) at dorsal root ganglia (DRG) by inhibiting NGF or its dual receptors. Sprague-Dawley rats with multiply punctured L5-L6 IVD were used. Six experimental groups were prepared: naïve, sham control, and four agent-treated groups with punctured IVD (vehicle, anti-NGF antibody, anti-TrkA antibody, and anti-p75(NTR) antibody). Retrograde neurotracer Fluoro-Gold (FG) was applied together except for the naïve group. Their lumbar DRG were harvested and immunolabeled for CGRP. FG-labeled DRG neurons were most prevalent at L1 and L2 DRG, and the proportion of FG-labeled CGRP-immunoreactive DRG neurons in the vehicle group was significantly elevated (p < 0.05) compared with the sham group, while those of antibody-treated groups, especially in the anti-p75(NTR) group, significantly decreased compared with the vehicle group (p < 0.05). Direct intradiscal application of antibody to NGF or its receptors suppressed CGRP expression, and p75(NTR) antagonism induced the most profound suppression.
Orita
Sumihisa
S
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. sumihisa@silver.email.ne.jp
Ohtori
Seiji
S
Nagata
Maiko
M
Horii
Manato
M
Yamashita
Masaomi
M
Yamauchi
Kazuyo
K
Inoue
Gen
G
Suzuki
Munetaka
M
Eguchi
Yawara
Y
Kamoda
Hiroto
H
Arai
Gen
G
Ishikawa
Tetsuhiro
T
Miyagi
Masayuki
M
Ochiai
Nobuyasu
N
Kishida
Shunji
S
Takaso
Masashi
M
Aoki
Yasuchika
Y
Takahashi
Kazuhisa
K
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D015536:Down-Regulation; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D007403:Intervertebral Disc / Q000294:innervation; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000294:innervation; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology
D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide