Decreased calcitonin gene-related peptide expression in the dorsal root ganglia of TNF-deficient mice in a monoiodoacetate-induced knee osteoarthritis model.

Abstract

BACKGROUND:

The detailed mechanisms of knee osteoarthritis (OA) pain have not been clarified, but involvement of inflammatory cytokines such as tumor necrosis factor-alpha (TNF) has been suggested. The present study aimed to investigate the more detailed neurological involvement of TNF in joint pain using a TNF-knockout mouse OA model.

METHODS:

The right knees of twelve-week-old C57BL/6J wild and TNF-deficient knockout (TNF-ko) mice (n=15, each group) were given a single intra-articular injection of 10 µg monoiodoacetate in 10 mL sterile saline. The left knees were only punctured as the control. Evaluations were performed immediately after the injection (baseline) and at 7, 14, and 28 days after the injection with a subsequent intra-articular injection of neurotracer into both knees. The animals were evaluated for immunofluorescence of the lumbar dorsal root ganglia (DRG) innervating the knee joints. The injected knees were observed macroscopically and mouse pain-related behaviors were scored.

RESULTS:

Macroscopic observation showed similar knee OA development in both wild and TNF-ko mice. Calcitonin gene-related peptide (CGRP, a neuropeptide identified as a inflammatory pain-related biomarker) was significantly increased in DRG neurons innervating OA-induced knee joints with significantly less CGRP expression in TNF-ko animals. Pain-related behavior scoring showed a significant increase in pain in OA-induced joints, but there was no significant difference in pain observed between the wild and TNF-ko mice.

CONCLUSIONS:

The result of the present study indicates the possible association of TNF-alpha in OA pain but not OA development.

• Authors: Aya Taniguchi, Tetsuhiro Ishikawa, Masayuki Miyagi, Hiroto Kamoda, Yoshihiro Sakuma, Yasuhiro Oikawa, Go Kubota, Kazuhide Inage, Takeshi Sainoh, Junichi Nakamura, Yasuchika Aoki, Tomoaki Toyone, Gen Inoue, Miyako Suzuki, Kazuyo Yamauchi, Takane Suzuki, Kazuhisa Takahashi, Seiji Ohtori, Sumihisa Orita
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 10 Pg. 12967-71 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26722492 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Tumor Necrosis Factor-alpha
• Calcitonin Gene-Related Peptide
• Iodoacetic Acid

Topics

• Animals
• Arthritis, Experimental (chemically induced, complications, metabolism)
• Calcitonin Gene-Related Peptide (biosynthesis)
• Disease Models, Animal
• Enzyme Inhibitors (toxicity)
• Fluorescent Antibody Technique
• Ganglia, Spinal (metabolism)
• Iodoacetic Acid (toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Osteoarthritis, Knee (chemically induced, complications, metabolism)
• Pain (etiology, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)