Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University, Stanford, California, USA.
Headache. 2022 Jul;62(7):780-791. doi: 10.1111/head.14352. Epub 2022 Jul 13.
Our laboratory has recently shown that there is a decrease in neuronal complexity in head pain processing regions in mouse models of chronic migraine-associated pain and aura. Importantly, restoration of this neuronal complexity corresponds with anti-migraine effects of known and experimental pharmacotherapies. The objective of the current study was to expand this work and examine other brain regions involved with pain or emotional processing. We also investigated the generalizability of our findings by analyzing neuronal cytoarchitectural changes in a model of complex regional pain syndrome (CRPS), a peripheral pain disorder.
We used the nitroglycerin (NTG) model of chronic migraine-associated pain in which mice receive 10 mg/kg NTG every other day for 9 days. Cortical spreading depression (CSD), a physiological corelate of migraine aura, was evoked in anesthetized mice using KCl. CRPS was induced by tibial fracture followed by casting. Neuronal cytoarchitecture was visualized with Golgi stain and analyzed with Simple Neurite Tracer.
In the NTG model, we previously showed decreased neuronal complexity in the trigeminal nucleus caudalis (TNC) and periaqueductal gray (PAG). In contrast, we found increased neuronal complexity in the thalamus and no change in the amygdala or caudate putamen in this study. Following CSD, we observed decreased neuronal complexity in the PAG, in line with decreases in the somatosensory cortex and TNC reported with this model previously. In the CRPS model there was decreased neuronal complexity in the hippocampus, as reported by others; increased complexity in the PAG; and no change within the somatosensory cortex.
Collectively these results demonstrate that alterations in neuronal complexity are a feature of both chronic migraine and chronic CRPS. However, each type of pain presents a unique cytoarchitectural signature, which may provide insight on how these pain states differentially transition from acute to chronic conditions.
本实验室最近发现，在慢性偏头痛相关疼痛和先兆的小鼠模型中，头部疼痛处理区域的神经元复杂性降低。重要的是，这种神经元复杂性的恢复与已知和实验性药物治疗的抗偏头痛作用相对应。本研究的目的是扩展这项工作，并研究其他涉及疼痛或情绪处理的大脑区域。我们还通过分析复杂区域疼痛综合征（CRPS）模型中的神经元细胞结构变化来研究我们发现的普遍性，CRPS 是一种外周疼痛障碍。
我们使用硝酸甘油（NTG）慢性偏头痛相关疼痛模型，其中小鼠每隔一天接受 10mg/kg NTG 治疗，共 9 天。在麻醉小鼠中使用 KCl 诱发皮质扩散性抑制（CSD），这是偏头痛先兆的生理相关物。通过胫骨骨折加铸型诱导 CRPS。使用高尔基染色可视化神经元细胞结构，并使用 Simple Neurite Tracer 进行分析。
在 NTG 模型中，我们之前曾显示三叉神经尾核（TNC）和导水管周围灰质（PAG）的神经元复杂性降低。相比之下，我们在这项研究中发现丘脑的神经元复杂性增加，而杏仁核或尾状核壳状体没有变化。在 CSD 后，我们观察到 PAG 的神经元复杂性降低，与以前该模型报道的感觉皮层和 TNC 减少一致。在 CRPS 模型中，海马的神经元复杂性降低，正如其他人所报道的那样；PAG 的复杂性增加；感觉皮层无变化。
这些结果表明，神经元复杂性的改变是慢性偏头痛和慢性 CRPS 的共同特征。然而，每种类型的疼痛都表现出独特的细胞结构特征，这可能有助于了解这些疼痛状态如何从急性向慢性状态不同地转变。
