title: 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: METHODS
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  Our results suggest that p75NTR contributes to neuropathic pain associated with BPA, and that inhibition of p75NTR reduces neuropathic pain.
  
  
  METHODS
  N/A.
authors: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. y-m-1211@khaki.plala.or.jp
authors: Yusuke
authors: Y
authors: Matsuura
authors: Nahoko
authors: N
authors: Iwakura
authors: Seiji
authors: S
authors: Ohtori
authors: Takane
authors: T
authors: Suzuki
authors: Kazuki
authors: K
authors: Kuniyoshi
authors: Kenichi
authors: K
authors: Murakami
authors: Ryo
authors: R
authors: Hiwatari
authors: Ken
authors: K
authors: Hashimoto
authors: Seiji
authors: S
authors: Okamoto
authors: Masataka
authors: M
authors: Shibayama
authors: Tomoko
authors: T
authors: Kobayashi
authors: Yasufumi
authors: Y
authors: Ogawa
authors: Kouji
authors: K
authors: Sukegawa
authors: Kazuhisa
authors: K
authors: Takahashi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D020516:Brachial Plexus Neuropathies / Q000378:metabolism / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005684:Gait / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D016138:Walking / Q000502:physiology
chemical_list: C491049:Aif1 protein, mouse; D000906:Antibodies; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat