Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
J Neurosci. 2011 Apr 6;31(14):5477-82. doi: 10.1523/JNEUROSCI.0328-11.2011.
Structural and functional plastic changes in the primary somatosensory cortex (S1) have been observed following peripheral nerve injury that often leads to neuropathic pain, which is characterized by tactile allodynia. However, remodeling of cortical connections following injury has been believed to take months or years; this is not temporally correlated with the rapid development of allodynia and S1 hyperexcitability. Here we first report, by using long-term two-photon imaging of postsynaptic dendritic spines in living adult mice, that synaptic connections in the S1 are rewired within days following sciatic nerve ligation through phase-specific and size-dependent spine survival/growth. Spine turnover in the S1 area corresponding to the injured paw markedly increased during an early phase of neuropathic pain and was restored in a late phase of neuropathic pain, which was prevented by immediate local blockade of the injured nerve throughout the early phase. New spines that generated before nerve injury showed volume decrease after injury, whereas more new spines that formed in the early phase of neuropathic pain became persistent and substantially increased their volume during the late phase. Further, preexisting stable spines survived less following injury than controls, and such lost persistent spines were smaller in size than the surviving ones, which displayed long-term potentiation-like enlargement over weeks. These results suggest that peripheral nerve injury induces rapid and selective remodeling of cortical synapses, which is associated with neuropathic pain development, probably underlying, at least partially, long-lasting sensory changes in neuropathic subjects.
初级体感皮层 (S1) 中的结构和功能可塑性变化在周围神经损伤后观察到，这通常会导致神经性疼痛，其特征是触觉过敏。然而，损伤后皮质连接的重塑被认为需要数月或数年的时间；这与痛觉过敏和 S1 过度兴奋的快速发展没有时间相关性。在这里，我们首先通过在活体成年小鼠中进行长期双光子成像突触后树突棘，报告了在坐骨神经结扎后几天内，通过特定相位和大小依赖性的棘突存活/生长，S1 中的突触连接被重新布线。在神经性疼痛的早期阶段，对应受伤爪子的 S1 区域的棘突周转率明显增加，并且在神经性疼痛的晚期阶段恢复，在早期阶段通过对受伤神经进行持续局部阻断可以预防这种情况。在神经损伤之前产生的新棘突在损伤后体积减小，而在神经性疼痛的早期阶段形成的更多新棘突变得持久，并在晚期阶段显著增加其体积。此外，损伤后预先存在的稳定棘突比对照物存活得更少，并且这些丢失的持久棘突比存活的棘突小，存活的棘突在数周内显示出长时程增强样增大。这些结果表明，周围神经损伤诱导皮质突触的快速和选择性重塑，这与神经性疼痛的发展有关，可能至少部分地解释了神经性患者的长期感觉变化。
