利塞膦酸钠和运动对骨质疏松性腰椎大鼠椎体及其感觉神经支配的影响。

The effects of risedronate and exercise on osteoporotic lumbar rat vertebrae and their sensory innervation.

机构信息

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

出版信息

Spine (Phila Pa 1976). 2010 Oct 15;35(22):1974-82. doi: 10.1097/BRS.0b013e3181d5959e.

DOI:10.1097/BRS.0b013e3181d5959e

PMID:20959778

Abstract

STUDY DESIGN

Investigation of sensory innervation of rat osteoporotic lumbar vertebrae using in vitro and in vivo models.

OBJECTIVE

To investigate (1) sensory innervation of osteoporotic rat vertebrae, (2) effects of risedronate on sensory neurons, (3) effects of osteoporosis treatment on bone mineral densities (BMDs) and the sensory innervation.

SUMMARY OF BACKGROUND DATA

Osteoporotic patients without fractures sometimes experience vague low back pain of unknown origin. The mechanisms of osteoporosis treatments against the pain are unclear.

METHODS

(1) The expression of calcitonin gene-related peptide (CGRP) immunoreactive (-ir) or transient receptor potential vanilloid 1 (TRPV1)-ir nerve fibers in vertebrae and dorsal root ganglions (DRG) innervating L3 vertebrae of Sprague Dawley rats labeled with neurotracer were examined in control, sham, and ovariectomized (OVX) rats. (2) Cultured rat neonate DRG neurons in media containing different concentrations of risedronate were immunostained for CGRP, and we measured its activity using axonal length and proportion of CGRP-ir neurons. (3) BMDs and CGRP expression in DRG neurons innervating L3 vertebrae were examined in the following 5 groups: sham (treated with saline), OVX (saline), OVX+EXE (treadmill exercise), OVX+RIS (risedronate), and OVX+RIS+EXE (risedronate and exercise).

RESULTS

(1) A few CGRP-ir or TRPV1-ir nerve fibers were observed in the bone marrow. CGRP or TRPV1 expression in DRG was elevated in the OVX group (P < 0.05). (2) The axonal length and proportion of CGRP-ir neurons were dose-dependently suppressed (P < 0.05). (3) BMDs improved and the CGRP expression decreased in the risedronate-treated groups (P < 0.05), especially in the OVX+RIS+EXE group.

CONCLUSION

Sensory innervation of osteoporotic rat vertebrae showed increased expression of CGRP and TRPV1 in DRG neurons. Risedronate suppressed activity of CGRP-ir neurons in vitro, improved BMD, and decreased CGRP expression, especially together with exercise in vivo.

摘要

研究设计

使用体外和体内模型研究大鼠骨质疏松性腰椎的感觉神经支配。

目的

研究（1）骨质疏松大鼠椎体的感觉神经支配，（2）利塞膦酸钠对感觉神经元的影响，（3）骨质疏松症治疗对骨密度（BMD）和感觉神经支配的影响。

背景资料概要

没有骨折的骨质疏松症患者有时会出现不明原因的模糊腰痛。骨质疏松症治疗疼痛的机制尚不清楚。

方法

（1）用神经示踪剂标记 L3 椎体的 Sprague Dawley 大鼠的椎体和背根神经节（DRG）中表达降钙素基因相关肽（CGRP）免疫反应（-ir）或瞬时受体电位香草素 1（TRPV1）-ir 神经纤维，观察对照组、假手术组和卵巢切除（OVX）组大鼠的情况。（2）在含有不同浓度利塞膦酸钠的培养基中培养新生大鼠 DRG 神经元，用免疫染色法检测 CGRP，并测量其活性，包括轴突长度和 CGRP-ir 神经元的比例。（3）在以下 5 组中检查支配 L3 椎体的 DRG 神经元的 BMD 和 CGRP 表达：假手术（用生理盐水处理）、OVX（生理盐水）、OVX+EXE（跑步机运动）、OVX+RIS（利塞膦酸钠）和 OVX+RIS+EXE（利塞膦酸钠和运动）。

结果

（1）骨髓中观察到少量 CGRP-ir 或 TRPV1-ir 神经纤维。DRG 中的 CGRP 或 TRPV1 表达在 OVX 组中升高（P < 0.05）。（2）轴突长度和 CGRP-ir 神经元的比例呈剂量依赖性抑制（P < 0.05）。（3）利塞膦酸钠治疗组的 BMD 改善，CGRP 表达降低（P < 0.05），尤其是在 OVX+RIS+EXE 组。