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Abstract
Background Osteoporosis may cause not only fractures but also chronic back pain in elderly women. Bente reported that postmenopausal women with severe osteoporosis who were prescribed teriparatide (TPTD) in standard clinical practice had a reduction in back pain. However, there have been no reports regarding the effect of TPTD on pain in animal models of osteoporosis.
Objectives The objective of the current study was to investigate the effect of TPTD on pain-related behavior in ovariectomized (OVX) mice.
Methods Female ddY mice (8 weeks old) were ovariectomized and assigned to 3groups; SHAM-operated mice treated with vehicle (SHAM), OVX mice treated with vehicle (OVX), OVX mice treated with TPTD (TPTD).
Starting immediately after surgery, vehicle or 40μg/kg TPTD was injected subcutaneously 5 times a week for 4 weeks.
The proximal tibial metaphysis were analyzed three-dimensionally by μCT 4 weeks after surgery (each group; 8 mice).
Mechanical sensitivity was tested using von Frey filaments 4 weeks after surgery. To evaluate the withdrawal threshold, each von Frey filaments was applied once, starting with 0.008g and increasing until a withdrawal response was reached, which was considered a positive response. The lowest force producing a response was considered the withdrawal threshold. To evaluate the 50% withdrawal threshold, seven von Frey filaments were applied to the middle of the plantar surface. Testing was initiated with the 0.6g filament. In the absence of a clear paw withdrawal response, increasingly stronger filaments were presented consecutively, until one of them was found to elicit such a response. If the 0.6 g filament elicited a response, filaments with decreasing strength were presented until determination of the first one which failed to cause paw withdrawal. Data was collected using the up-down method.
To identify osteoclasts in hindlimb bone, we used the tartrate-resistant acid phosphatase (TRAP) method. TRAP-positive multinucleated cells were scored as osteoclasts. Measurements were made within an area the proximal tibial metaphysis starting immediately below the growth plate. Histomorphometry was conducted to quantify the number of osteoclasts.
Results μCT analysis of the proximal tibial metaphysis showed that bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) were significantly less in the OVX group than in the SHAM group, whereas trabecular separation (Tb.Sp) was significantly greater in the OVX group than in the SHAM group. In the TPTD group, BV/TV and Tb.N were significantly greater than in the OVX group, whereas Tb.Sp was significantly less than in the OVX group.
The withdrawal threshold was significantly lower in the OVX group than in the SHAM group, and it was significantly higher in the TPTD group than in the OVX group. Similarly, the 50% withdrawal threshold was significantly lower in the OVX group than in the SHAM group, and it was significantly higher in the TPTD group than in the OVX group.
The number of osteoclasts was significantly higher in the OVX group than in the SHAM group, whereas it was higher in the TPTD group than in the OVX group, but there were no significantly changes.
Conclusions TPTD prevented ovariectomy-induced bone loss. In addition, mechanical hyperalgesia in hindlimbs significantly improved in OVX group compared with TPTD group. The results suggest that TPTD prevented postmenopausal osteoporotic pain.
Disclosure of Interest None declared