Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki, Japan.
Mol Pain. 2011 Nov 9;7:87. doi: 10.1186/1744-8069-7-87.
Postsynaptic dendritic spines in the cortex are highly dynamic, showing rapid morphological changes including elongation/retraction and formation/elimination in response to altered sensory input or neuronal activity, which achieves experience/activity-dependent cortical circuit rewiring. Our previous long-term in vivo two-photon imaging study revealed that spine turnover in the mouse primary somatosensory (S1) cortex markedly increased in an early development phase of neuropathic pain, but was restored in a late maintenance phase of neuropathic pain. However, it remains unknown how spine morphology is altered preceding turnover change and whether gain and loss of presynaptic boutons are changed during neuropathic pain.
Here we used short-term (2-hour) and long-term (2-week) time-lapse in vivo two-photon imaging of individual spines and boutons in the S1 cortical layer 1 of the transgenic mice expressing GFP in pyramidal neurons following partial sciatic nerve ligation (PSL). We found in the short-term imaging that spine motility (Δ length per 30 min) significantly increased in the development phase of neuropathic pain, but returned to the baseline in the maintenance phase. Moreover, the proportion of immature (thin) and mature (mushroom) spines increased and decreased, respectively, only in the development phase. Long-term imaging data showed that formation and elimination of boutons moderately increased and decreased, respectively, during the first 3 days following PSL and was subsequently restored.
Our results indicate that the S1 synaptic structures are rapidly destabilized and rearranged following PSL and subsequently stabilized in the maintenance phase of neuropathic pain, suggesting a novel therapeutic target in intractable chronic pain.
皮质中的突触后树突棘具有高度动态性，能够快速发生形态变化，包括伸长/回缩以及形成/消除，以响应感觉输入或神经元活动的改变，从而实现经验/活动依赖性皮质回路重连。我们之前的长期在体双光子成像研究表明，在神经病理性疼痛的早期发展阶段，小鼠初级体感（S1）皮质中的棘突周转率显著增加，但在神经病理性疼痛的晚期维持阶段恢复正常。然而，在棘突周转率改变之前，棘突形态如何改变，以及在神经病理性疼痛期间，突触前末梢是否发生增减，仍不清楚。
在这里，我们使用了短期（2 小时）和长期（2 周）时间 lapse 在体双光子成像技术，对表达 GFP 的转基因小鼠 S1 皮质 1 层中的单个棘突和末梢进行成像，这些小鼠在坐骨神经结扎（PSL）后，其锥体神经元中表达 GFP。我们在短期成像中发现，在神经病理性疼痛的发展阶段，棘突运动性（每 30 分钟的长度变化）显著增加，但在维持阶段恢复到基线。此外，只有在发展阶段，不成熟（细）和成熟（蘑菇）棘突的比例分别增加和减少。长期成像数据显示，在 PSL 后前 3 天，末梢的形成和消除分别适度增加和减少，随后恢复正常。
我们的研究结果表明，在 PSL 后 S1 突触结构迅速失稳并重新排列，随后在神经病理性疼痛的维持阶段稳定下来，这为治疗难治性慢性疼痛提供了新的治疗靶点。
