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.

Abstract

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.

• Authors: Yusuke Matsuura, Nahoko Iwakura, Seiji Ohtori, Takane Suzuki, Kazuki Kuniyoshi, Kenichi Murakami, Ryo Hiwatari, Ken Hashimoto, Seiji Okamoto, Masataka Shibayama, Tomoko Kobayashi, Yasufumi Ogawa, Kouji Sukegawa, Kazuhisa Takahashi
• Journal: Spine (Spine (Phila Pa 1976)) Vol. 38 Issue 6 Pg. E332-8 (Mar 15 2013) ISSN: 1528-1159 [Electronic] United States
• PMID: 23324933 (Publication Type: Journal Article)

Chemical References

• Aif1 protein, mouse
• Antibodies
• Calcium-Binding Proteins
• Glial Fibrillary Acidic Protein
• Microfilament Proteins
• Nerve Tissue Proteins
• Receptors, Growth Factor
• Receptors, Nerve Growth Factor
• Ngfr protein, rat

Topics

• Animals
• Antibodies (immunology, pharmacology)
• Astrocytes (drug effects, metabolism)
• Brachial Plexus Neuropathies (metabolism, physiopathology)
• Calcium-Binding Proteins (metabolism)
• Disease Models, Animal
• Gait (drug effects, physiology)
• Ganglia, Spinal (drug effects, metabolism, physiopathology)
• Glial Fibrillary Acidic Protein (metabolism)
• Hyperalgesia (physiopathology, prevention & control)
• Immunohistochemistry
• Male
• Microfilament Proteins (metabolism)
• Microglia (drug effects, metabolism, physiology)
• Nerve Tissue Proteins
• Pain (physiopathology, prevention & control)
• Rats
• Rats, Wistar
• Receptors, Growth Factor
• Receptors, Nerve Growth Factor (antagonists & inhibitors, immunology, metabolism)
• Walking (physiology)