• Miyako Suzuki, Sumihisa Orita, Masayuki Miyagi, Tetsuhiro Ishikawa, Hiroto Kamoda, Yawara Eguchi, Gen Arai, Kazuyo Yamauchi, Yoshihiro Sakuma, Yasuhiro Oikawa, Go Kubota, Kazuhide Inage, Takeshi Sainoh, Yuya Kawarai, Kensuke Yoshino, Tomoyuki Ozawa, Yasuchika Aoki, Tomoaki Toyone, Kazuhisa Takahashi, Mamoru Kawakami, Seiji Ohtori, and Gen Inoue.
• 1Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University 2Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center 3Department of Orthopaedic Surgery, Toho University Sakura Medical Center 4Department of Orthopaedic Surgery, Wakayama Medical University Kihoku hospital 5Department of Orthopaedic Surgery, Kitasato University School of Medicine.
• Spine. 2013 Sep 10.

AbstractStudy Design. Basic pain study using osteoporotic rodent models.Objective. To examine alterations in distribution of pain-related neuropeptides following compressive force on osteoporotic vertebrae and their chronic pain-related properties.Summary of Background Data. We previously reported significantly increased production of calcitonin gene-related peptide (CGRP), a marker of inflammatory pain, in the dorsal root ganglia (DRG) of vertebrae in osteoporosis-model ovariectomized (OVX) rats. Here, we hypothesized that longitudinal compressive force on vertebrae can affect osteoporotic pain properties, which has not been examined yet.Methods. OVX rats were used as the osteoporosis model. Female Sprague Dawley rats were prepared and Fluoro-Gold (FG) neurotracer was applied to the periosteal surface of the Co5 vertebra. After FG-labeling, the animals were divided into 4 groups: Control, Control + compression, OVX, and OVX + compression. The Control groups were not ovariectomized. In the compression groups, K-wires were stabbed transversely through Co4 and Co6 with Co5 compressed longitudinally by rubber bands bridged between the two. One, 2, 4, and 8 weeks after surgery, bilateral S1 to S3 DRGs were excised for immunofluorescence assays. Expression of CGRP and activating transcription factor 3 (ATF-3), a marker of neuronal injury, were compared among the 4 groups.Results. Sustained upregulation of CGRP in DRG neurons was observed following compression of the Co5 vertebra, and Co5 compression caused significant increase in CGRP production in DRG neurons, while a greater level of ATF-3 upregulation was observed in DRGs in OVX rats following dynamic vertebral compression 8 weeks after surgery, implying potential neuropathic pain.Conclusion: There was sustained upregulation of CGRP and ATF3 in DRGs in osteoporotic model rats compared with controls, and levels were further enhanced by dynamic vertebral compression. These findings imply that dynamic compression stress on vertebrae can exacerbate osteoporotic pain by inducing both inflammatory and neuropathic pain mediators.

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