The Effect of Anti-NGF Receptor (p75 Neurotrophin Receptor) Antibodies on Nociceptive Behavior and Activation of Spinal Microglia in the Rat Brachial Plexus Avulsion Model
| Autor: | Yasufumi Ogawa, Nahoko Iwakura, Yusuke Matsuura, Ken Hashimoto, Masataka Shibayama, Kenichi Murakami, Seiji Okamoto, Kouji Sukegawa, Kazuhisa Takahashi, Tomoko Kobayashi, Ryo Hiwatari, Takane Suzuki, Kazuki Kuniyoshi, Seiji Ohtori |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Tanezumab Pain Nerve Tissue Proteins Receptors Nerve Growth Factor Walking Antibodies chemistry.chemical_compound Ganglia Spinal Internal medicine Glial Fibrillary Acidic Protein medicine Animals Low-affinity nerve growth factor receptor Receptors Growth Factor Orthopedics and Sports Medicine Rats Wistar Brachial Plexus Neuropathies Gait Microglia Glial fibrillary acidic protein biology business.industry Calcium-Binding Proteins Microfilament Proteins Spinal cord Immunohistochemistry Rats Disease Models Animal medicine.anatomical_structure Nociception Endocrinology chemistry Hyperalgesia Astrocytes Anesthesia Neuropathic pain biology.protein sense organs Neurology (clinical) medicine.symptom business |
| Zdroj: | Spine. 38:E332-E338 |
| ISSN: | 0362-2436 |
| DOI: | 10.1097/brs.0b013e318285ee20 |
| Popis: | Study design We measured the response of the behavior and spinal glial activation to anti-nerve growth factor receptor (p75 neurotrophin receptor [p75NTR]) antibodies in the rat brachial plexus avulsion (BPA) model. Objective The aim of this study was to investigate the effect of anti-p75NTR antibodies on nociceptive behavior and activation of spinal microglia in the rat BPA model. Summary of background data Tanezumab (anti-nerve growth factor antibody) treatment is associated with pain reduction and improvement in function, but with several complications. Methods Thirty male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level and 10 μL of saline was applied locally (n = 10). In the anti-p75NTR group, the C8-T1 roots were avulsed and 10 μL of anti-p75NTR antibody was applied locally (n = 10). In a sham-operated group, the lower trunk was simply exposed (n = 10). Mechanical hyperalgesia and pain-induced walking patterns were measured using von Frey filaments (Stoelting, Wood Dale, IL) and the CatWalk gait analysis (Noldus Information Technology, the Netherlands) system every third day for 3 weeks. Activation of astrocytes and microglia was immunohistochemically examined in the spinal cord using anti-glial fibrillary acidic protein (GFAP) and anti-Iba1 antibodies both 7 and 21 days after surgery. Results Animals in the BPA group displayed significant mechanical hyperalgesia that continued through day 21 compared with animals in the sham-operated group, and mechanical hyperalgesia in the anti-p75NTR group was significantly improved 6 days after the operation. Regarding pain-induced gait analysis via CatWalk, animals in the BPA group displayed a significantly greater pain-like gait pattern than the p75 group for up to 3 weeks. Levels of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia in the anti-p75NTR group were significantly reduced compared with the BPA group. Conclusion Our results suggest that p75NTR contributes to neuropathic pain associated with BPA, and that inhibition of p75NTR reduces neuropathic pain. Level of evidence N/A. |
| Databáze: | OpenAIRE |
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