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Teriparatide improves pain-related behavior and prevents bone loss in ovariectomized mice
Sho Kato1, Hiroki Wakabayashi1, Taro Nakagawa1
1Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan.
Purpose:
The aim of this study was to examine the inhibitory effect of teriparatide (TPTD) on pain and on bone loss in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated through an examination of pain-related behavior as well as immunohistochemical examinations.
Methods:
Eight-week-old female ddY mice were OVX and assigned to one of three groups: (1) OVX mice treated with vehicle (OVX), (2) OVX mice treated with teriparatide (OVX-TPTD), or (3) SHAM-operated mice treated with vehicle (SHAM). Starting immediately after surgery, vehicle or TPTD was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was tested using von Frey filaments. The proximal tibial metaphyses were analyzed three-dimensionally by microcomputed tomography (μCT). Calcitonin gene-related peptide (CGRP) and transient receptor potential channel vanilloid 1 (TRPV1) expressions in L3-5 dorsal root ganglion (DRG) neurons were examined using immunohistochemistry.
Results:
Ovariectomy induced bone loss and mechanical hyperalgesia in the hind limbs with upregulation of CGRP and TRPV1 expressions in DRG neurons innervating the hind limbs. Bone loss was prevented more effectively in the OVX-TPTD mice than in the OVX mice. Furthermore, mechanical hyperalgesia and upregulation of CGRP and TRPV1 expressions were significantly lower in the OVX-TPTD mice than in the OVX mice.
Conclusion:
TPTD treatment prevented ovariectomy-induced bone loss and ovariectomy-induced mechanical hyperalgesia in hind limbs, and it suppressed CGRP and TRPV1 expressions in DRG neurons. These results suggest that TPTD is useful for the treatment of osteoporotic pain in postmenopausal women.
Insights
Teriparatide (TPTD) effectively treats bone loss and pain in ovariectomized (OVX) mice. TPTD suppressed pain-related gene expression, indicating its potential for treating osteoporotic pain.
Area of Science:
- Biomedical research
- Osteoporosis research
- Pain management
Background:
- Ovariectomy (OVX) in mice leads to bone loss and pain.
- Osteoporotic pain mechanisms involve specific gene expressions in neurons.
Purpose of the Study:
- To investigate teriparatide's (TPTD) inhibitory effects on bone loss and pain in OVX mice.
- To elucidate the mechanism of osteoporotic pain in OVX mice.
Main Methods:
- OVX mice were treated with TPTD or vehicle.
- Mechanical sensitivity was assessed using von Frey filaments.
- Bone structure was analyzed using microcomputed tomography (μCT).
- Gene expression of CGRP and TRPV1 in dorsal root ganglion (DRG) neurons was examined via immunohistochemistry.
Main Results:
- OVX induced bone loss and mechanical hyperalgesia, with increased CGRP and TRPV1 expression.
- TPTD treatment significantly prevented bone loss and reduced mechanical hyperalgesia in OVX mice.
- TPTD suppressed the upregulation of CGRP and TRPV1 in DRG neurons.
Conclusions:
- TPTD effectively mitigates ovariectomy-induced bone loss and associated pain.
- The study suggests TPTD's therapeutic potential for osteoporotic pain in postmenopausal women.
- Inhibition of CGRP and TRPV1 expression is a key mechanism for TPTD's analgesic effect.
