• Masahiro Suzuki, Kazuhide Inage, Yoshihiro Sakuma, Sumihisa Orita, Kazuyo Yamauchi, Takane Suzuki, Miyako Suzuki, Go Kubota, Yasuhiro Oikawa, Takeshi Sainoh, Jun Sato, Kazuki Fujimoto, Yasuhiro Shiga, Koki Abe, Hirohito Kanamoto, Kazuhisa Takahashi, and Seiji Ohtori.
• Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan.
• Injury. 2016 Mar 1; 47 (3): 609-12.

IntroductionAlthough muscle injury is a common source of pain, the mechanism causing such pain is not completely known. We have previously reported nerve growth factor (NGF) as a proinflammatory mediator involved in acute pain, and clinical trials have shown the effectiveness of anti-NGF antibodies for management of low back pain. Here, we aim to examine the effects of anti-NGF antibodies on muscle-derived pain by studying their effects on sensory innervation in a rat muscle injury model.MethodsA nervous system tracer, Fluoro-Gold, was applied to both gastrocnemius muscles of 24 male Sprague Dawley rats to stain the sensory nerves. Then, the drop-mass method was used to damage the right gastrocnemius muscle of the posterior limb. Anti-NGF antibodies (50μL) were injected into the injured muscles in 12 rats. Tissues were evaluated 1, 3, and 7 days post-injury by performing haematoxylin-and-eosin (HE) staining. The percentage of the total number of FG-positive cells that were also positive for a pain-related neuropeptide, calcitonin gene-related peptide (CGRP), was determined for the bilateral dorsal root ganglia from L1 to L6 7 days post-injury.ResultsHE staining showed active inflammation, indicated by increased basophil and eosinophil accumulation, at the injury site 1 and 3 days post-injury, as well as scar tissue formation 7 days post-injury. Injection of anti-NGF reduced muscle necrosis 1 and 3 days post-injury, and resulted in replacement of granulation tissue and muscle fibre regeneration 7 days post-injury. Anti-NGF also significantly inhibited CGRP among FG-positive cells (treatment group 38.2%, control group 49.6%; P<0.05).DiscussionThis study found active inflammation induced by NGF, which may contribute to pain after muscle injury. Anti-NGF antibodies successfully suppressed the pain mediator NGF and inhibited inflammation, suggesting NGF as a target for control in pain management.Copyright © 2015 Elsevier Ltd. All rights reserved.

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