PDF(Pubmed)
Abstract：
BACKGROUND: Methylmercury (MeHg), the causative agent of Minamata disease, damages the cranial nervous system and causes specific sensory disturbances, especially hypoesthesia, in the extremities. However, recent reports demonstrate that patients with chronic Minamata disease conversely develop neuropathic pain in the lower extremities. Studies on our established Minamata disease model rats showed that MeHg-mediated neurodegeneration might induce neuropathic pain by over time through inducing rewiring with neuronal activation in the somatosensory cortex via microglial activation in the spinal dorsal horn.
METHODS: In this study, the effects of gabapentin, a potentially effective treatment for neuropathic pain, was evaluated using this Minamata disease model rats. To further elucidate the mechanism of its medicinal effects, histochemical and biochemical analyses of the nervous system of Minamata disease model rats were conducted.
RESULTS: Gabapentin treatment restored the reduction in the pain threshold caused by MeHg exposure in rats. Histochemical and biochemical analyses revealed that gabapentin showed no effect on MeHg-induced neurodegeneration in entire nervous system and microglial activation in the spinal dorsal horn. However, it was shown that gabapentin may reduce excessive synaptogenesis through its antagonist action on the alpha2-delta-1 subunit of calcium channels in the somatosensory cortex.
CONCLUSIONS: These results indicate that gabapentin may alleviated neuropathic pain in MeHg poisoning, as typified by Minamata disease, by reversibly modulation synaptic rewiring in the somatosensory cortex.
METHODS: In this study, the effects of gabapentin, a potentially effective treatment for neuropathic pain, was evaluated using this Minamata disease model rats. To further elucidate the mechanism of its medicinal effects, histochemical and biochemical analyses of the nervous system of Minamata disease model rats were conducted.
RESULTS: Gabapentin treatment restored the reduction in the pain threshold caused by MeHg exposure in rats. Histochemical and biochemical analyses revealed that gabapentin showed no effect on MeHg-induced neurodegeneration in entire nervous system and microglial activation in the spinal dorsal horn. However, it was shown that gabapentin may reduce excessive synaptogenesis through its antagonist action on the alpha2-delta-1 subunit of calcium channels in the somatosensory cortex.
CONCLUSIONS: These results indicate that gabapentin may alleviated neuropathic pain in MeHg poisoning, as typified by Minamata disease, by reversibly modulation synaptic rewiring in the somatosensory cortex.
摘要：
背景：甲基汞（MeHg），水生病的病原体，损害颅神经系统并引起特定的感觉障碍，尤其是感觉减退,在四肢。然而,最近的报道表明，慢性水晶病患者相反会在下肢发生神经性疼痛。对我们建立的水晶病模型大鼠的研究表明，MeHg介导的神经变性可能会随着时间的推移，通过脊髓背角的小胶质细胞激活，诱导体感皮层中神经元激活的重新布线，从而引起神经性疼痛。
方法：在本研究中，加巴喷丁的作用,一种治疗神经性疼痛的潜在有效方法，使用该水晶病模型大鼠进行评价。为了进一步阐明其药效机制,对水峰病模型大鼠的神经系统进行了组织化学和生化分析。
结果：加巴喷丁治疗恢复了由甲基汞暴露引起的大鼠疼痛阈值的降低。组织化学和生化分析表明，加巴喷丁对MeHg引起的整个神经系统的神经变性和脊髓背角的小胶质细胞活化没有影响。然而,研究表明，加巴喷丁可以通过其对体感皮层钙通道α2-δ-1亚基的拮抗作用来减少过度的突触发生。
结论：这些结果表明加巴喷丁可以减轻甲基汞中毒的神经性疼痛，以水生病为代表，通过可逆地调节体感皮层的突触重新布线。
方法：在本研究中，加巴喷丁的作用,一种治疗神经性疼痛的潜在有效方法，使用该水晶病模型大鼠进行评价。为了进一步阐明其药效机制,对水峰病模型大鼠的神经系统进行了组织化学和生化分析。
结果：加巴喷丁治疗恢复了由甲基汞暴露引起的大鼠疼痛阈值的降低。组织化学和生化分析表明，加巴喷丁对MeHg引起的整个神经系统的神经变性和脊髓背角的小胶质细胞活化没有影响。然而,研究表明，加巴喷丁可以通过其对体感皮层钙通道α2-δ-1亚基的拮抗作用来减少过度的突触发生。
结论：这些结果表明加巴喷丁可以减轻甲基汞中毒的神经性疼痛，以水生病为代表，通过可逆地调节体感皮层的突触重新布线。
