Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord.
Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord.
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DOI：
10.1186/1744-8069-6-38
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发表时间：
2010-07-05
期刊：
影响因子：
3.3
通讯作者：
Yoshimura M
中科院分区：
文献类型：
--
作者：
Yanagisawa Y;Furue H;Kawamata T;Uta D;Yamamoto J;Furuse S;Katafuchi T;Imoto K;Iwamoto Y;Yoshimura M
慢性骨癌疼痛被认为部分是由于中枢致敏。尽管骨癌疼痛的小鼠模型揭示了脊髓中显著的神经化学变化，但尚不清楚这是否会导致脊髓感觉突触传递的功能改变。在这项研究中，我们研究了兴奋性突触反应诱发的胶状质（SG，板II）神经元在成年小鼠脊髓切片的骨癌，使用全细胞电压钳记录技术。在肉瘤植入股骨后14至21天，小鼠对施加于同侧后爪皮肤的机械刺激表现出痛觉过敏，以及表现出自发和运动诱发的疼痛相关行为。SG神经元表现出自发兴奋性突触后电流（EPSC）。荷癌小鼠自发性EPSC的幅度明显大于对照组，而SG神经元的被动膜特性无任何变化。在TTX的存在下，SG神经元中的微型EPSC的振幅在荷癌小鼠中增加，并且这在广泛的腰椎节段水平上的细胞采样中观察到。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体和N-甲基-D-天冬氨酸（NMDA）受体介导的EPSCs在荷癌小鼠中也被增强。背根刺激引起单突触和/或多突触EPSC，其由来自两组动物的SG神经元中的A δ和/或C传入纤维的激活引起。接受A δ和C纤维单突触输入的细胞数在两组之间没有差异。而荷瘤小鼠单突触C纤维诱发的EPSC的幅度和接受A δ和C纤维多突触输入的SG神经元数目增加。这些结果表明，通过A δ和C纤维介导的脊髓突触传递在股骨肉瘤植入后，在SG中跨越腰椎节段的广泛区域增强。这种广泛的脊髓致敏可能是慢性骨癌疼痛发展的潜在机制之一。
Chronic bone cancer pain is thought to be partly due to central sensitization. Although murine models of bone cancer pain revealed significant neurochemical changes in the spinal cord, it is not known whether this produces functional alterations in spinal sensory synaptic transmission. In this study, we examined excitatory synaptic responses evoked in substantia gelatinosa (SG, lamina II) neurons in spinal cord slices of adult mice bearing bone cancer, using whole-cell voltage-clamp recording techniques. Mice at 14 to 21 days after sarcoma implantation into the femur exhibited hyperalgesia to mechanical stimuli applied to the skin of the ipsilateral hind paw, as well as showing spontaneous and movement evoked pain-related behaviors. SG neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs). The amplitudes of spontaneous EPSCs were significantly larger in cancer-bearing than control mice without any changes in passive membrane properties of SG neurons. In the presence of TTX, the amplitude of miniature EPSCs in SG neurons was increased in cancer-bearing mice and this was observed for cells sampled across a wide range of lumbar segmental levels. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor- and N-methyl-D-aspartate (NMDA) receptor-mediated EPSCs evoked by focal stimulation were also enhanced in cancer-bearing mice. Dorsal root stimulation elicited mono- and/or polysynaptic EPSCs that were caused by the activation of Aδ and/or C afferent fibers in SG neurons from both groups of animals. The number of cells receiving monosynaptic inputs from Aδ and C fibers was not different between the two groups. However, the amplitude of the monosynaptic C fiber-evoked EPSCs and the number of SG neurons receiving polysynaptic inputs from Aδ and C fibers were increased in cancer-bearing mice. These results show that spinal synaptic transmission mediated through Aδ and C fibers is enhanced in the SG across a wide area of lumbar levels following sarcoma implantation in the femur. This widespread spinal sensitization may be one of the underlying mechanisms for the development of chronic bone cancer pain.
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影响因子：
2.5
作者：
Light, AR;Willcockson, HH
通讯作者：
Willcockson, HH
影响因子：
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