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

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. 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. Tanezumab (anti-nerve growth factor antibody) treatment is associated with pain reduction and improvement in function, but with several complications. 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. 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. Our results suggest that p75NTR contributes to neuropathic pain associated with BPA, and that inhibition of p75NTR reduces neuropathic pain. N/A.