The Effects of Generally Administered Anti–Nerve Growth Factor Receptor (p75NTR) Antibody on Pain-Related Behavior, Dorsal Root Ganglia, and Spinal Glia Activation in a Rat Model of Brachial Plexus Avulsion

• Published in: The Journal of hand surgery (American ed.) Vol. 40; no. 10; pp. 2017 - 2025
• Main Authors: Kobayashi, Tomoko, MD, PhD, Yamauchi, Kazuyo, MD, PhD, Matsuura, Yusuke, MD, PhD, Kuniyoshi, Kazuki, MD, PhD, Takahashi, Kazuhisa, MD, PhD, Ohtori, Seiji, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015
• Subjects: Animals; Behavior, Animal - drug effects; Brachial Plexus - drug effects; Brachial Plexus - injuries; Brachial plexus avulsion; Brachial Plexus Neuropathies - diagnosis; Brachial Plexus Neuropathies - drug therapy; Disease Models, Animal; DRG; glial cell; Injections, Intraperitoneal; Male; Neuralgia - drug therapy; Neuroglia - drug effects; neuropathic pain; Orthopedics; p75NTR; Pain Measurement; Pain Threshold - drug effects; Random Allocation; Rats; Rats, Wistar; Receptor, Nerve Growth Factor - administration & dosage; Receptor, Nerve Growth Factor - antagonists & inhibitors; Sensitivity and Specificity; Spinal Nerve Roots - drug effects; Statistics, Nonparametric; DRG; p75NTR; neuropathic pain; glial cell; Brachial plexus avulsion
• ISSN: 0363-5023; 1531-6564
• DOI: 10.1016/j.jhsa.2015.06.008

Purpose To investigate the effect of intraperitoneal administration of an anti-p75 neurotrophin receptor (p75NTR) antibody on reducing neuropathic pain in a rat model of brachial plexus avulsion (BPA). Methods We randomly assigned 40 male Wistar rats to 4 groups. In the BPA group, the C8-T1 roots were avulsed from the spinal cord at the lower trunk level, and saline was administered intraperitoneally. In the anti-p75NTR groups, 1 μL or 50 μL anti-p75NTR antibody was administered intraperitoneally after avulsion. In the sham-operated group, the lower trunk level was exposed, and saline was administered intraperitoneally. Mechanical hyperalgesia and pain-induced walking patterns were measured using von Frey filaments and CatWalk gait analysis at various time points until 15 days after administration. At 3 and 15 days after administration, sensory neurons involved in pain perception and satellite glial cells in the ipsilateral C7 dorsal root ganglia were immunolabeled with antibodies against calcitonin gene-related peptide and glial fibrillary acidic protein (GFAP), respectively. At both time points, microglial and astrocyte activation, indicative of spinal pain transmission, were immunohistochemically examined in the ipsilateral dorsal horn of the spinal cord (C7) using anti-ionized calcium-binding adaptor molecule 1 and anti-GFAP antibodies, respectively. Results The gait pattern was significantly improved in both anti-p75NTR groups compared with the BPA group. There were significantly fewer calcitonin gene-related peptide-immunoreactive (IR) neurons, neurons encircled by GFAP-IR satellite glial cells, and GFAP-IR astrocytes in both anti-p75NTR groups compared with the BPA group at both time points. Fewer ionized calcium-binding adaptor molecule 1-IR microglia were quantified in both anti-p75NTR groups compared with the BPA group, but this was only significant at 15 days after administration. Conclusions Systemic application of the p75NTR inhibitory antibody suppressed neuropathic pain after BPA. Clinical relevance p75NTR may be a potential therapeutic target for the clinical treatment of neuropathic pain in BPA injury.