Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
Division of Occupational Therapy, Department of Rehabilitation, Orthopaedic Trauma Center, Sapporo Tokushu-Kai Hospital, 1-1, Oyachi East-1, Atsubetsu-ku, Sapporo, 004-0041, Japan.
J Bone Miner Metab. 2020 Jul;38(4):469-480. doi: 10.1007/s00774-020-01086-1. Epub 2020 Feb 4.
Cold intolerance is defined as abnormal pain resulting from exposure to cold stimulation after trauma. However, the pathophysiology remains unclear. We recently demonstrated that regional osteoporotic changes accompanied by high bone turnover were involved in causing pain-like behaviors in the unloaded hind limbs of tail-suspended mice. Bisphosphonate prevented pain-like behaviors and high bone turnover conditions in tail-suspended mice. The aims of this study were to examine the relationship between regional osteoporotic changes and the induction of hypersensitivity to cold stimulation.
The hind limbs of tail-suspended mice were unloaded for 2 weeks. The von Frey test and paw-flick test assessed pain-like behaviors and cold plate test evaluated cold escape behaviors. Furthermore, we examined whether cold hypersensitivity associated with regional osteoporotic changes could be improved by bisphosphonate, TRPV1 and TRPA1 antagonists.
Hypersensitivity to cold stimulation was induced more noticeably in the tail-suspended mice, and this effect was related to the increased expression of bone metabolism markers. In addition, the cold hypersensitivity was improved by the resumption of weight bearing and prevented by bisphosphonate or a TRPV1 antagonist, and was accompanied with a decrease in the expression of bone metabolism markers. TRPA1 antagonist significantly improved the cold escape behavior, but had no significant effects on the expression of those markers.
We demonstrated that the regional osteoporotic changes accompanying a high bone turnover state could be involved in the induction of hypersensitivity to cold stimulation in the tail-suspended mice.
冷不耐受被定义为创伤后暴露于冷刺激时引起的异常疼痛。然而，其病理生理学仍不清楚。我们最近的研究表明，区域骨质疏松变化伴有高骨转换参与了导致尾部悬吊小鼠未负重后肢产生类痛行为。双膦酸盐可预防尾部悬吊小鼠的类痛行为和高骨转换状态。本研究的目的是研究区域骨质疏松变化与冷刺激诱导的敏感性增加之间的关系。
尾部悬吊小鼠的后肢悬吊 2 周。von Frey 测试和爪拍测试评估类痛行为，冷板测试评估冷逃避行为。此外，我们还研究了双膦酸盐、TRPV1 和 TRPA1 拮抗剂是否能改善与区域骨质疏松变化相关的冷敏感。
冷刺激敏感性在尾部悬吊小鼠中更明显地增加，这种效应与骨代谢标志物表达的增加有关。此外，恢复承重可改善冷敏感，双膦酸盐或 TRPV1 拮抗剂可预防冷敏感，同时骨代谢标志物的表达降低。TRPA1 拮抗剂显著改善冷逃避行为，但对这些标志物的表达无显著影响。
我们证明了伴随高骨转换状态的区域骨质疏松变化可能参与了尾部悬吊小鼠冷刺激敏感性的诱导。
