Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Laboratory of Veterinary Anatomy, Faculty of Applied Biological Sciences, Gifu University, Yanagido, Gifu, Japan.
Folia Neuropathol. 2020;58(2):151-165. doi: 10.5114/fn.2020.96800.
Spina bifida aperta (SBA), one of the most common congenital malformations, causes various neurological disorders. Pain is a common complaint of patients with SBA. However, little is known about the neuropathology of SBA-related pain. Because loss of g-aminobutyric acid GABAergic neurons in the spinal cord dorsal horn is associated with pain, we hypothesised the existence of crosstalk between SBA-related pain and alterations in GABAergic transmission in the spinal cord. Therefore, we investigated the kinetics of GABAergic transmission in the spinal cord dorsal horn in a chicken model of SBA. Neonatal chicks with SBA exhibited various pain-like behaviours, such as an increased number of vocalisations with elevated intensity (loudness) and frequency (pitch), reduced mobility, difficulty with locomotion, and escape reactions. Furthermore, the chicks with SBA did not respond to standard toe-pinching, indicating disruption of the spinal cord sensorimotor networks. These behavioural observations were concomitant with loss of GABAergic transmission in the spinal cord dorsal horn. We also found apoptosis of GABAergic neurons in the superficial dorsal horn in the early neonatal period, although cellular abnormalisation and propagation of neuro-degenerative signals were evident at middle to advanced gestational stages. In conclusion, ablation of GABAergic neurons induced alterations in spinal cord neuronal networks, providing novel insights into the pathophysiology of SBA-related pain-like complications.
开放性脊柱裂（SBA）是最常见的先天性畸形之一，可导致各种神经障碍。疼痛是 SBA 患者的常见主诉。然而，SBA 相关疼痛的神经病理学知之甚少。由于脊髓背角中 γ-氨基丁酸（GABA）能神经元的丧失与疼痛有关，我们假设 SBA 相关疼痛与脊髓中 GABA 能传递的改变之间存在串扰。因此，我们在 SBA 鸡模型中研究了脊髓背角中 GABA 能传递的动力学。患有 SBA 的新生小鸡表现出各种类似疼痛的行为，例如发声次数增加（响度）和频率（音调）增加、活动减少、运动困难和逃避反应。此外，患有 SBA 的小鸡对标准的脚趾夹捏没有反应，表明脊髓感觉运动网络受损。这些行为观察与脊髓背角中 GABA 能传递的丧失同时发生。我们还发现早期新生儿期脊髓背角浅层中 GABA 能神经元凋亡，尽管在中晚期妊娠阶段可见细胞异常化和神经退行性信号的传播。总之，GABA 能神经元的缺失导致脊髓神经元网络的改变，为 SBA 相关疼痛样并发症的病理生理学提供了新的见解。
