Comparison of mechanisms of allodynia induced by acromelic acid A between early and late phases.
Comparison of mechanisms of allodynia induced by acromelic acid A between early and late phases.
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DOI：
10.1016/j.ejphar.2015.03.075
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发表时间：
2015-08
影响因子：
5
通讯作者：
Haruka Omoto;S. Matsumura;Manabu Kitano;S. Miyazaki;T. Minami;S. Ito
中科院分区：
文献类型：
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作者：
Haruka Omoto;S. Matsumura;Manabu Kitano;S. Miyazaki;T. Minami;S. Ito
我们以前表明，鞘内注射丙烯酸A（ACRO-A）引起小鼠触觉异常性疼痛。近年来的研究表明，NMDA谷氨酸受体-神经元型一氧化氮合酶（nNOS）通路和胶质细胞的激活在神经病理性疼痛的发生和维持中起着重要作用。为了阐明它们参与ACRO-A诱导的异常性疼痛，我们研究了各种药物对两种小鼠模型在早期和晚期异常性疼痛的影响。所用药物为Ca 2+通道α2δ配体、NMDA和AMPA受体拮抗剂、nNOS和Ca 2 +/钙调蛋白激酶II抑制剂。当与ACRO-A同时注射时，所有这些药物在早期组中阻断了异常性疼痛;然而，当在晚期组中ACRO-A给药后7天注射时，它们没有阻断异常性疼痛。为了阻断胶质细胞活化，给予星形胶质细胞抑制剂L-α-氨基己二酸酯（LAA）或小胶质细胞抑制剂米诺环素，并在第7天检查异常性疼痛。注射ACRO-A后1h或1周，用组织化学方法检测脊髓nNOS和胶质细胞的活化。我们发现注射ACRO-A后1小时nNOS活性增加;然而，注射ACRO-A后1周nNOS活性没有增加。相反，在ACRO-A注射后1周观察到小胶质细胞活化，并且米诺环素治疗显著抑制。此外，只有LAA被发现抑制晚期异常性疼痛，在这项研究中，我们证明，NMDA受体激活只参与ACRO-A诱导的触觉异常性疼痛的早期阶段，和脊髓星形胶质细胞激活有助于在晚期异常性疼痛。
We previously showed that intrathecal administration of acromelic acid A (ACRO-A) provoked tactile allodynia in mice. As well, recent studies have demonstrated that the activation of NMDA glutamate receptor-neuronal nitric oxide synthase (nNOS) pathway and glia play crucial roles in the development and maintenance of neuropathic pain. In order to clarify their involvement in ACRO-A-induced allodynia, we investigated the effects of various agents on two mouse models at early and late-phase allodynia. The agents employed were Ca2+channel α2δ ligands, NMDA and AMPA receptor antagonists, nNOS, and Ca2+/calmodulin kinase II inhibitors. When injected simultaneously with ACRO-A, all of these agents blocked allodynia in the early-phase group; however, they did not block allodynia when injected 7 days after the administration of ACRO-A in the late-phase group. In order to block glial activation, astrocytic inhibitor L-α-aminoadipate (LAA) or microglial inhibitor minocycline was administrated, and allodynia was examined on day 7. Activations of nNOS and glia in the spinal cord were histochemically examined at 1 h or 1 week after injection of ACRO-A. We found that nNOS activity increased 1 h after ACRO-A injection; however, it did not increase 1 week after ACRO-A injection. Conversely, microglial activation was observed 1 week after ACRO-A injection and was significantly inhibited with minocycline treatment. Moreover, only LAA was found to inhibit late-phase allodynia.In this study, we demonstrate that NMDA receptor activation is involved only in ACRO-A-induced tactile allodynia in the early phase, and that spinal astrocytic activation contributes to allodynia in the late phase.