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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.

Authors: Matsuura, Y  Iwakura, N  Ohtori, S  Suzuki, T  Kuniyoshi, K  Murakami, K  Hiwatari, R  Hashimoto, K  Okamoto, S  Shibayama, M  Kobayashi, T  Ogawa, Y  Sukegawa, K  Takahashi, K 
Citation: Matsuura Y, etal., Spine (Phila Pa 1976). 2013 Mar 15;38(6):E332-8. doi: 10.1097/BRS.0b013e318285ee20.
Pubmed: (View Article at PubMed) PMID:23324933
DOI: Full-text: DOI:10.1097/BRS.0b013e318285ee20

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 muL of saline was applied locally (n = 10). In the anti-p75NTR group, the C8-T1 roots were avulsed and 10 muL 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.

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RGD Object Information
RGD ID: 10413898
Created: 2015-11-30
Species: All species
Last Modified: 2015-11-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.