Vertebral compression exacerbates osteoporotic pain in an ovariectomy-induced osteoporosis rat model.
METHODS
Basic pain study using osteoporotic rodent models.


OBJECTIVE
To examine alterations in distribution of pain-related neuropeptides after compressive force on osteoporotic vertebrae and their chronic pain-related properties.


BACKGROUND
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 2. 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, a marker of neuronal injury, were compared among the 4 groups.


RESULTS
Sustained upregulation of CGRP in DRG neurons was observed after compression of the Co5 vertebra, and Co5 compression caused significant increase in CGRP production in DRG neurons, whereas a greater level of activating transcription factor 3 upregulation was observed in DRGs in OVX rats after dynamic vertebral compression 8 weeks after surgery, implying potential neuropathic pain.


CONCLUSIONS
There was sustained upregulation of CGRP and activating transcription factor 3 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.


METHODS
N/A.
*Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan; †Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Ichihara, Japan; ‡Department of Orthopaedic Surgery, Toho University Sakura Medical Center, Sakura, Japan; §Department of Orthopaedic Surgery, Wakayama Medical University Kihoku Hospital, Wakayama, Japan; and ¶Department of Orthopaedic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
Miyako
M
Suzuki
Sumihisa
S
Orita
Masayuki
M
Miyagi
Tetsuhiro
T
Ishikawa
Hiroto
H
Kamoda
Yawara
Y
Eguchi
Gen
G
Arai
Kazuyo
K
Yamauchi
Yoshihiro
Y
Sakuma
Yasuhiro
Y
Oikawa
Go
G
Kubota
Kazuhide
K
Inage
Takeshi
T
Sainoh
Yuya
Y
Kawarai
Kensuke
K
Yoshino
Tomoyuki
T
Ozawa
Yasuchika
Y
Aoki
Tomoaki
T
Toyone
Kazuhisa
K
Takahashi
Mamoru
M
Kawakami
Seiji
S
Ohtori
Gen
G
Inoue
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D058128:Compression Bandages / Q000009:adverse effects; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010024:Osteoporosis / Q000209:etiology / Q000503:physiopathology*; D010052:Ovariectomy / Q000009:adverse effects; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013122:Spinal Diseases / Q000209:etiology / Q000503:physiopathology*; D013131:Spine / Q000503:physiopathology*; D013314:Stress, Mechanical
D051700:Activating Transcription Factor 3; D015740:Calcitonin Gene-Related Peptide