Background Factors of chronic pain due to hemiplegia or prolonged immobility are varied, there is osteoporosis (a rarefaction due to bone atrophy) as the cause. Osteoporotic patients with no evidence of fractures sometimes experience vague lower back pain. However, there have been few reports regarding the correlation between osteoporosis and pain-related behavior. Our previous studies have indicated that hindlimb-unloading induced bone loss and mechanical hyperalgesia in hindlimb of mice. We investigated the effects of teriparatide (PTH) on bone mass and pain-related behaviors in osteoporosis model mice with hindlimb unloading.
Objectives The objective of the current study was to investigate the effect of PTH on bone mass and pain-related behaviors in hindlimb-unloaded mice model of disuse osteoporosis.
Methods Male ddY mice (8 weeks old) were tail-suspended for 2 weeks and assigned to 3 groups; hindlimb-loaded mice treated with vehicle (control), hindlimb-unloaded mice treated with vehicle (HU), hindlimb-unloaded mice treated with PTH (HU-PTH)
(n=8/group). Starting immediately after tail-suspension, vehicle or 40μg/kg PTH was injected subcutaneously twice a week for 2 weeks. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally by micro-computed tomography (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. Measurement of pain-related behavior with von Frey filaments was interpreted as indicative of mechanical allodynia.
Results μCT analysis of the distal femoral metaphysis and the proximal tibial metaphysis showed that significantly decreased bone volume/tissue volume (BV/TV) and trabecular thickness (Tb.Th) in HU compared with HL was significantly increased by PTH treatment. (Fig.1) Similarly, decreased trabecular number (Tb.N) in HU compared with HL was increased, and increased trabecular separation (Tb.Sp) in HU compared with HL was decreased by PTH treatment, but not significant. The paw withdrawal threshold and the 50% paw withdrawal threshold were significantly lower in the HU than in the control, whereas it was significantly higher in the HU-PTH than in the HU group. (Fig.2) The paw withdrawal frequency stimulated by von Frey filaments with strength of 0.4–2.0 g was significantly higher in the HU than in the control. Whereas it was significantly lower in the HU-PTH than in the HU.
Conclusions In this study, treatment of PTH prevented bone loss and mechanical hyperalgesia in disuse osteoporotic animal models by hindlimb-unloading. The results suggest that low bone volume itself is one of the causes of osteoporotic pain.
Disclosure of Interest None declared