Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
Bone. 2018 May;110:284-294. doi: 10.1016/j.bone.2018.02.006. Epub 2018 Feb 14.
Our recent studies demonstrated that regional bone loss in the unloaded hind limbs of tail-suspended mice triggered pain-like behaviors due to the acidic environment in the bone induced by osteoclast activation. The aims of the present study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are expressed in bone, and whether the antagonists to those receptors affect the expression of osteoblast and osteoclast regulators, and prevent the triggering of not only pain-like behaviors but also high bone turnover conditions in tail-suspension model mice. The hind limb-unloaded mice were subjected to tail suspension with the hind limbs elevated for 14days. The effects of the TRPV1, ASIC3, P2X2/3 antagonists on pain-like behaviors as assessed by the von Frey test, paw flick test and spontaneous pain scale; the expressions of TRPV1, ASICs, and P2X2 in the bone; and the effects of those antagonists on osteoblast and osteoclast regulators were examined. In addition, we evaluated the preventive effect of continuous treatment with a TRPV1 antagonist on the trigger for pain-like behavior and bone loss in tail-suspended mice. Pain-like behaviors were significantly improved by the treatment with TRPV1, ASIC, P2X antagonists; TRPV1, ASICs and P2X were expressed in the bone tissues; and the antagonists to these receptors down-regulated the expression of osteoblast and osteoclast regulators in tail-suspended mice. In addition, continuous treatment with a TRPV1 antagonist during tail-suspension prevented the induction of pain-like behaviors and regional bone loss in the unloaded hind limbs. We, therefore, believe that those receptor antagonists have a potential role in preventing the triggering of skeletal pain with associated regional bone metabolic disorder.
我们最近的研究表明，由于破骨细胞激活引起的酸性环境，尾部悬吊小鼠未负重后肢的局部骨丢失会引发类似疼痛的行为。本研究旨在研究 TRPV1、ASIC 和 P2X（称为伤害感受器）是否在骨中表达，以及这些受体的拮抗剂是否会影响成骨细胞和破骨细胞调节剂的表达，并预防不仅是尾部悬吊模型小鼠的类似疼痛行为的触发，还有高骨转换状态的触发。将后肢去负荷的小鼠用后腿抬高进行 14 天的尾部悬吊。通过 von Frey 测试、爪拍测试和自发疼痛量表评估 TRPV1、ASIC3、P2X2/3 拮抗剂对类似疼痛行为的影响；评估骨中 TRPV1、ASICs 和 P2X2 的表达；以及这些拮抗剂对成骨细胞和破骨细胞调节剂的影响。此外，我们评估了连续用 TRPV1 拮抗剂治疗对尾部悬吊小鼠类似疼痛行为和骨丢失触发的预防作用。TRPV1、ASIC、P2X 拮抗剂的治疗显著改善了类似疼痛行为；TRPV1、ASICs 和 P2X 在骨组织中表达；并且这些受体的拮抗剂下调了尾部悬吊小鼠成骨细胞和破骨细胞调节剂的表达。此外，在尾部悬吊期间连续用 TRPV1 拮抗剂治疗可预防未负重后肢的类似疼痛行为和局部骨丢失的诱导。因此，我们认为这些受体拮抗剂在预防与局部骨代谢紊乱相关的骨骼疼痛触发方面具有潜在作用。
