Kingery Wade S, Offley Sarah C, Guo Tian-Zhi, Davies M Frances, Clark J David, Jacobs Christopher R
Physical Medicine and Rehabilitation Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Bone. 2003 Dec;33(6):927-36. doi: 10.1016/j.bone.2003.07.003.
The long-term effects of sciatic nerve section on bone mineral density (BMD) were studied using dual-energy X-ray absorptiometry (DEXA) in skeletally mature rats. Unilateral sciatic neurectomy caused the rapid loss of cancellous bone in the proximal and distal femur and tibia in the ipsilateral hindlimb and, to a lesser extent, in the contralateral intact hindlimb. The reduction in BMD rapidly progressed for 4 weeks after sciatic section and then gradually stabilized with no evidence of recovery at 12 weeks. The development of osteoporosis in the contralateral intact hindlimb was a novel finding. There was no evidence of disuse in the normal contralateral hindlimb after unilateral sciatic section; grid-crossing activity over a 24-h interval was unchanged and there was no reduction in weight bearing on the contralateral normal hindpaw during the stance phase of ambulation. Unilateral peripheral nerve lesions have well-documented effects on substance P content and function in the corresponding contralateral intact nerve. We hypothesized that after sciatic section a reduction in substance P signaling might contribute to bone loss in the contralateral hindlimb. Daily administration of the substance P receptor (NK1) antagonist LY303870 for 2 weeks caused significant loss of cancellous bone in the denervated and the contralateral hindlimb, evidence that substance P signaling sustained bone density after nerve section. After sciatic neurectomy there was a 33% reduction in sciatic nerve stimulation-evoked extravasation in the contralateral intact hindlimb, indicating transmedian inhibition of substance P signaling after nerve injury. Furthermore, there was a 50% reduction in the substance P content in both tibias after unilateral sciatic section. Collectively, these data support the hypothesis that a widespread reduction in substance P content in bone contributes to the osteoporotic effects of sciatic neurectomy and that residual substance P signaling maintains bone integrity after nerve section in both the denervated and contralateral intact hindlimb.
利用双能X线吸收法（DEXA），在骨骼成熟的大鼠中研究了坐骨神经切断对骨密度（BMD）的长期影响。单侧坐骨神经切除术导致同侧后肢股骨近端和远端以及胫骨的松质骨迅速流失，对侧完整后肢的流失程度较小。坐骨神经切断后，骨密度的降低在4周内迅速进展，然后逐渐稳定，在12周时没有恢复的迹象。对侧完整后肢发生骨质疏松是一个新发现。单侧坐骨神经切断后，对侧正常后肢没有废用的迹象；24小时内的网格交叉活动没有变化，在行走的站立阶段，对侧正常后爪的负重也没有减少。单侧周围神经损伤对相应对侧完整神经中的P物质含量和功能有充分记录的影响。我们假设，坐骨神经切断后，P物质信号的减少可能导致对侧后肢的骨质流失。每天给予P物质受体（NK1）拮抗剂LY303870两周，导致去神经支配和对侧后肢的松质骨显著流失，这证明P物质信号在神经切断后维持骨密度。坐骨神经切除术后，对侧完整后肢中坐骨神经刺激诱发的血管外渗减少了33%，表明神经损伤后P物质信号的经中抑制。此外，单侧坐骨神经切断后，两侧胫骨中的P物质含量减少了50%。总体而言，这些数据支持以下假设：骨中P物质含量的广泛减少导致坐骨神经切除术的骨质疏松效应，并且残余的P物质信号在去神经支配和对侧完整后肢的神经切断后维持骨的完整性。
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