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Inhibiting nerve growth factor or its receptors downregulates calcitonin gene‐related peptide expression in rat lumbar dorsal root ganglia innervating injured intervertebral discs
Author(s) -
Orita Sumihisa,
Ohtori Seiji,
Nagata Maiko,
Horii Manato,
Yamashita Masaomi,
Yamauchi Kazuyo,
Inoue Gen,
Suzuki Munetaka,
Eguchi Yawara,
Kamoda Hiroto,
Arai Gen,
Ishikawa Tetsuhiro,
Miyagi Masayuki,
Ochiai Nobuyasu,
Kishida Shunji,
Takaso Masashi,
Aoki Yasuchika,
Takahashi Kazuhisa
Publication year - 2010
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21170
Subject(s) - calcitonin gene related peptide , nerve growth factor , tropomyosin receptor kinase a , receptor , calcitonin , medicine , endocrinology , dorsal root ganglion , substance p , neuropeptide , anatomy , dorsum
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. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1614–1620, 2010