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Efficacy of anti-nerve growth factor therapy for discogenic neck pain in rats
Takeshi Sainoh1, Yoshihiro Sakuma, Masayuki Miyagi
1*Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan †Department of Orthopaedic Surgery, Kitasato University, Kanagawa, Japan ‡Department of Orthopaedic Surgery, Chiba Cancer Center, Chiba, Japan §Department of Orthopaedic Surgery, Sammu Medical Center, Chiba, Japan ¶Department of Orthopaedic Surgery, Toho University Sakura Medical Center, Chiba, Japan; and ‖Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.
Study Design:
Immunohistological analysis of the cervical dorsal root ganglia (DRG).
Objective:
To investigate immunohistologically in rats whether intradiscal administration of anti-nerve growth factor (NGF) antibody in injured cervical intervertebral discs (IVDs) suppresses pain-related peptide expression in DRG neurons.
Summary Of Background Data:
Neck pain can involve the entire neck and become chronic and intractable. Cervical disc degeneration is a primary cause of neck pain, and pain-related mediators, such as NGF, have been correlated with discogenic pain.
Methods:
We examined Sprague-Dawley rats that received 10 punctures in the C5-C6 IVD, and were treated with saline (puncture group) or an anti-NGF antibody (anti-NGF group). The retrograde neurotracer Fluoro-Gold (FG) was then injected into the C5-C6 IVD. In addition, we examined a sham group that did not receive punctures (disc nonpuncture). The C2-C7 DRG were harvested 1 week after surgery and immunostained for calcitonin gene-related peptide (CGRP), a marker for peptide-containing neurons. We determined for each group the percentages of FG-labeled DRG neurons that were CGRP-immunoreactive (CGRP-ir).
Results:
FG-labeled neurons innervating the C5-C6 IVD were found in all C2-C7 DRG examined. The percentage of FG-labeled CGRP-ir DRG neurons in the puncture group was significantly higher than that observed in the sham (P < 0.001) and anti-NGF groups (P < 0.001), but there was no significant difference between the sham and anti-NGF groups (P > 0.05). Therefore, intradiscal administration of anti-NGF antibody suppressed CGRP expression the cervical DRG.
Conclusion:
Neurons located in the C2-C7 DRG innervated the C5-C6 IVD. These findings indicate that neck pain may be derived from degenerated IVDs. Furthermore, intradiscal administration of anti-NGF antibody suppressed CGRP expression in the cervical DRG innervating the injured IVD. Therefore, inhibiting NGF upregulation in the cervical IVD may be an efficient treatment for discogenic neck pain.
Level Of Evidence:
N/A.
