Involvement of increased excitatory amino acids and intracellular Ca2+ concentration in the spinal dorsal horn in an animal model of neuropathic pain
Involvement of increased excitatory amino acids and intracellular Ca2+ concentration in the spinal dorsal horn in an animal model of neuropathic pain
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DOI：
10.1016/s0304-3959(96)03222-8
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发表时间：
1996-11-01
期刊：
影响因子：
7.4
通讯作者：
Omote, K
中科院分区：
文献类型：
--
作者：
Kawamata, M;Omote, K
神经损伤后的神经病理性疼痛被认为涉及兴奋性氨基酸(EaaS)和钙离子介导的中枢神经系统(CNS)神经元可塑性变化。本研究旨在观察大鼠坐骨神经慢性缩窄性损伤(CCI)后脊髓背侧谷氨酸和天冬氨酸含量的变化。在同一动物模型中，我们还检测了脊髓横断切片中脊髓背角细胞内钙离子浓度([Ca~(2+)](I))的变化。在CCI后第2天和之后观察到热性和机械性痛敏(P<；0.0001)。在CCI大鼠中，腹腔注射0.5 mg/kg。MK-801在CCI前30分钟给药，随后每日3次，每次0.5 mg/kg。MK-801后，热痛敏和机械性痛敏的发展被抑制长达7天，但在IO天和14天出现痛敏(P<；0.001)。在慢性脑损伤大鼠，神经结扎后同侧背角谷氨酸和天冬氨酸含量在第4、7和14天显著升高(P<；0.001)。此外，脊髓薄片神经结扎后第4、7、14天，脊髓背角浅层(I-II层)和深层(V-VI层)的[Ca~(2+)](I)也显著升高(P<；0.0001)。静脉注射的治疗。MK-801在第4天和第7天抑制谷氨酸和天门冬氨酸含量及[Ca~(2+)](I)的升高，而同侧谷氨酸和天冬氨酸的含量在第14天显著升高(P分别为0.001和0.003)，在第14天也出现[Ca~(2+)](I)的升高(P<；0.001)，其增加区域的空间分布与未经治疗的大鼠相似。我们对这些结果的解释是，CCI诱导的大鼠神经病理性痛敏与谷氨酸和天冬氨酸含量增加以及随后激活NMDA受体，继而脊髓背角内[Ca~(2+)](I)增加有关。
Neuropathic pain following nerve injury is believed to involve excitatory amino acids (EAAs) and Ca2+-mediated neuronal plastic changes in the central nervous system (CNS). This study was designed to investigate the changes in glutamate and aspartate contents in the dorsal half of the spinal cord following chronic constrictive injury (CCI) of the rat common sciatic nerve. We also examined the changes in intracellular calcium ion concentration ([Ca2+](i)) of the spinal dorsal horn in transverse spinal slices in the same animal model. Thermal and mechanical hyperalgesia were observed on day 2 and thereafter following CCI (P < 0.0001). In the CCI rats to which 0.5 mg/kg of i.p. MK-801 was given 30 min prior to CCI and subsequently three daily treatments with 0.5 mg/kg of i.p. MK-801, the development of thermal and mechanical hyperalgesia was suppressed for a period of up to 7 days; however, hyperalgesia appeared on day IO and day 14 (P < 0.001). In CCI rats, significant increases were observed in glutamate and aspartate contents on the ipsilateral side of the dorsal horn to nerve ligation on days 4, 7 and 14 (P < 0.001). Moreover, significant increases in [Ca2+](i) in the spinal dorsal horn were also observed in the superficial (lamina I-II) and deep layers (lamina V-VI) on the ipsilateral side to nerve ligation on days 4, 7 and 14 after nerve ligation in the spinal slices (P < 0.0001). The treatment with i.p. MK-801 suppressed the increases in the contents of glutamate and aspartate and in [Ca2+](i) on days 4 and 7. However, the ipsilateral contents of glutamate and aspartate significantly increased on day 14 (P < 0.001 and 0.003, respectively); the increased [Ca2+](i) was also observed on day 14 (P < 0.001), and the spatial pattern of the increased regions was similar to untreated CCI rats. We interpret these results to indicate that neuropathic hyperalgesia induced by CCI in the rat is associated with an increase in glutamate and aspartate contents and the subsequent activation of NMDA receptors, followed by an increase in [Ca2+](i) within dorsal horn of the spinal cord.