Inhibiting nerve growth factor or its receptors downregulates calcitonin gene-related peptide expression in rat lumbar dorsal root ganglia innervating injured intervertebral discs
| Autor: | Kazuyo Yamauchi, Kazuhisa Takahashi, Yawara Eguchi, Masashi Takaso, Gen Inoue, Yasuchika Aoki, Tetsuhiro Ishikawa, Seiji Ohtori, Nobuyasu Ochiai, Maiko Nagata, Masaomi Yamashita, Gen Arai, Shunji Kishida, Munetaka Suzuki, Sumihisa Orita, Manato Horii, Masayuki Miyagi, Hiroto Kamoda |
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| Rok vydání: | 2010 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Calcitonin Gene-Related Peptide medicine.medical_treatment Down-Regulation Neuropeptide Nerve Tissue Proteins Intervertebral Disc Degeneration Receptors Nerve Growth Factor Tropomyosin receptor kinase A Calcitonin gene-related peptide Rats Sprague-Dawley Ganglia Spinal Internal medicine Nerve Growth Factor medicine Animals Low-affinity nerve growth factor receptor Receptors Growth Factor Orthopedics and Sports Medicine Intervertebral Disc Receptor Neurons Lumbar Vertebrae business.industry Growth factor Rats Nerve growth factor Endocrinology nervous system Calcitonin Female business |
| Zdroj: | Journal of Orthopaedic Research. 28:1614-1620 |
| ISSN: | 0736-0266 |
| Popis: | 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: naive, 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 naive 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. |
| Databáze: | OpenAIRE |
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