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FRI0306 Effects of Bisphosphonate for Pain-Related Behavior and Immunohistochemical Analysis in the Hind Limb-Unloaded Mouse Model of Disuse Osteoporosis
  1. T. Nakagawa1,2,
  2. H. Wakabayashi1,
  3. Y. Naito3,
  4. S. Kato1,
  5. T. Iino1,
  6. A. Sudo1
  1. 1Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu City, Mie
  2. 2Orthopaedic Surgery, Owase General Hospital, Owase City, Mie
  3. 3Orthopaedic Surgery, Kinan Hospital, Minamimuro District, Mie, Japan

Abstract

Background Osteoporotic patients with no evidence of fractures sometimes experience vague lower back pain. A previous report has indicated that sensory innervation of ovariectomized rat vertebrae showed increased expression of the CGRP, a neuropeptide marker of pain, and the TRPV1, an acid-sensitive ion channel, in dorsal root ganglion (DRG) neurons1. However, there have been few reports regarding the correlation between osteoporosis, pain-related behavior and immunohistochemical analysis.

Objectives The objective of the current study was to investigate pain-related behavior and to elucidate the mechanism of osteoporotic pain by immunohistochemical analysis of the DRG in hindlimb-unloaded (HU) mice model of disuse osteoporosis2. And we investigated the effect of alendronate (ALN) in HU mice.

Methods Male ddY mice (8 weeks old) were tail-suspended for 2 week and assigned to 3 groups; hindlimb-loaded mice treated with vehicle (control), HU mice treated with vehicle (HUV), HU mice treated with ALN (HUA)(n=8/group). Starting immediately after tail-suspension, vehicle or 40μg/kg ALN was injected subcutaneously twice a week for 2 weeks. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally by μCT 2 weeks after tail-suspension. Mechanical sensitivity was also tested using von Frey filaments 2 week after the tail suspension. The withdrawal threshold, the 50% withdrawal threshold and the frequency of the withdrawal response to the application of von Frey filaments to the plantar surface of the hind paws was examined. Immunohistochemical analysis of the CGRP expression and the TRPV1 expression was completed for the L4 and L5 DRG neurons.

Results μCT analysis of the distal femoral metaphysis (Fig. 1a) and the proximal tibial metaphysis showed that significantly decreased bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) in HUV compared with control was significantly increased by ALN treatment. Significantly increased trabecular separation (Tb.Sp) in HUV compared with control was significantly decreased by ALN treatment. The paw withdrawal threshold and the 50% paw withdrawal threshold were significantly lower in the HUV than in the control, whereas it was significantly higher in the HUA than in the HUV group (Fig. 1b). The paw withdrawal frequency stimulated by von Frey filaments with strength of 0.4–2.0 g was significantly higher in the HUV than in the control. Whereas it was significantly lower in the HUA than in the HUV. The immunohistochemical analysis showed that the ratio of CGRP-immunoreactive (ir) and TRPV1-ir DRG neurons (L4 and L5) in the HUV was significantly higher than in the control, whereas it was significantly lower in the HUA than in the HUV. There was no significant difference between the HUA and the control in μCT analysis, hyperalgesia of hindlimbs and immunohistochemical analysis.

Conclusions In this study, treatment of ALN prevented bone loss, mechanical hyperalgesia and upregulation of CGRP and TRPV1 expression in DRG neurons of disuse osteoporotic animals models by hindlimb-unloading. The results suggest that bone resorption is one of the causes of osteoporotic pain.

References

  1. Orita S et al. Spine. 2010.

  2. Barou O et al. Invest Radiol. 2002.

Disclosure of Interest None declared

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