Tranexamic acid evokes pain by modulating neuronal excitability in the spinal dorsal horn.
Tranexamic acid evokes pain by modulating neuronal excitability in the spinal dorsal horn.
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DOI：
10.1038/srep13458
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发表时间：
2015-08-21
影响因子：
4.6
通讯作者：
Kohno T
中科院分区：
文献类型：
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作者：
Ohashi N;Sasaki M;Ohashi M;Kamiya Y;Baba H;Kohno T
氨甲环酸（TXA）是一种抗纤维蛋白溶解剂，广泛用于减少手术期间的失血量。然而，TXA的严重不良反应是由于抑制皮质神经元中的γ-氨基丁酸（GABA）和甘氨酸受体而导致的癫痫发作。这些受体也存在于脊髓中，并且这些受体在脊髓背角神经元中的拮抗作用在实验动物中产生疼痛相关的现象，例如异常性疼痛和痛觉过敏。此外，一些鞘内注射TXA的患者会出现严重的背痛。然而，TXA对脊髓背角神经元的影响仍然知之甚少。在这里，我们通过对大鼠进行行为测量来研究TXA的作用，发现TXA会产生指示自发性疼痛和机械性异常疼痛的行为。然后，我们进行了全细胞膜片钳实验，表明TXA抑制脊髓背角神经元的GABAA和甘氨酸受体。最后，我们还表明，血栓素A促进激活的细胞外信号调节激酶在脊髓。这些结果表明，TXA通过抑制脊髓背角的GABAA和甘氨酸受体产生疼痛。
Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery. However, a serious adverse effect of TXA is seizure due to inhibition of γ-aminobutyric acid (GABA) and glycine receptors in cortical neurons. These receptors are also present in the spinal cord, and antagonism of these receptors in spinal dorsal horn neurons produces pain-related phenomena, such as allodynia and hyperalgesia, in experimental animals. Moreover, some patients who are injected intrathecally with TXA develop severe back pain. However, the effect of TXA on spinal dorsal horn neurons remain poorly understood. Here, we investigated the effects of TXA by using behavioral measures in rats and found that TXA produces behaviors indicative of spontaneous pain and mechanical allodynia. We then performed whole-cell patch-clamp experiments that showed that TXA inhibits GABAA and glycine receptors in spinal dorsal horn neurons. Finally, we also showed that TXA facilitates activation of the extracellular signal-regulated kinase in the spinal cord. These results indicated that TXA produces pain by inhibiting GABAA and glycine receptors in the spinal dorsal horn.