Neurite orientation dispersion and density imaging reveals brain microstructure alterations associated with hyperalgesia and emotional disorders in neuropathic

Emotional disorders such as depression that accompany neuropathic pain (NP) impair the patient's quality of life and cause hyperalgesia through the brain nuclei network called the pain matrix. Structural alteration in the pain matrix is an essential mechanism for the co-morbidity and the mutual regulation of hyperalgesia and emotional disorders in NP, yet microstructural alterations such as neurite characteristics remain unclear. Neurite orientation dispersion and density imaging (NODDI) is a magnetic resonance imaging (MRI) that can detect the microstructure alterations of the brain nucleus. Here, in the NP mouse model with emotional disorders, we detected microstructural alterations in the nuclei of pain matrix by NODDI. The results showed a decrease of neurite density index (NDI) and orientation dispersion index (ODI) in the anterior cingulate cortex layers 5-6 of CCI mice, which were related to hyperalgesia and depression-like behavior. We also found an increase of ODI in the ventral posterolateral and paraventricular nucleus of the thalamus and an increase of NDI in the central amygdala. These results may serve as a new addition to clinical diagnosis and mechanism research of NP.

神经性疼痛（NP）伴随的情感障碍，如抑郁症，严重损害患者的生存质量，并通过称为痛觉矩阵的脑核网络引起痛觉过敏。痛觉矩阵的结构变化是共病性和神经性疼痛中痛觉过敏与情感障碍相互调节的必要机制，然而，诸如神经突起特征等微观结构变化仍不明确。神经突起取向分布和密度成像（NODDI）是一种能够检测脑核微观结构变化的磁共振成像（MRI）。在本研究中，我们通过NODDI检测了具有情感障碍的神经性疼痛小鼠模型中痛觉矩阵的微观结构变化。结果显示，CCI小鼠的前扣带回皮层5-6层神经突起密度指数（NDI）和取向分散指数（ODI）降低，这与痛觉过敏和抑郁样行为相关。我们还发现在丘脑的腹侧后外侧核和室旁核中ODI增加，在中央杏仁核中NDI增加。这些结果可能为神经性疼痛的临床诊断和机制研究提供新的视角。