Involvement of spinal glutamate in nociceptive behavior induced by intrathecal administration of hemokinin-1 in mice

Involvement of spinal glutamate in nociceptive behavior induced by intrathecal administration of hemokinin-1 in mice
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DOI:
10.1016/j.neulet.2016.02.027
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发表时间:
2016-03
影响因子:
2.5
通讯作者:
C. Watanabe;H. Mizoguchi;G. Bagetta;S. Sakurada
C. Watanabe;H. Mizoguchi;G. Bagetta;S. Sakurada
中科院分区:
医学4区
文献类型:
--
作者:
C. Watanabe;H. Mizoguchi;G. Bagetta;S. Sakurada

文献摘要

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最近发现的速激肽,hemokinin-1,是从小鼠骨髓中克隆出来的。虽然多项研究表明 hemokinin-1 与疼痛和炎症有关,但 hemokinin-1 的生理功能尚不完全清楚。我们之前的研究表明,鞘内 (i.t.) 给予 hemokinin-1 (0.00625–1.6 nmol) 会剂量依赖性地诱发小鼠的伤害性行为,包括抓、咬和舔,这与 i.t. 诱发的伤害性行为非常相似。低剂量(0.0125 nmol)血激肽-1 诱导的伤害性行为被特定的 NK1 受体拮抗剂抑制;然而,高剂量(0.1 nmol)hemokinin-1 诱导的伤害性行为并未受到影响。在本研究中,我们发现 hemokinin-1(0.1 nmol)诱导的伤害性行为被 i.t 抑制。联合施用 MK-801 或 D-APV,它们是 NMDA 受体拮抗剂。此外,我们使用微透析测量了小鼠脊髓细胞外液中的谷氨酸。它。给予hemokinin-1可显着增加脊髓中的谷氨酸含量,而与NMDA受体拮抗剂共同施用则可显着降低谷氨酸含量。这些结果表明,hemokinin-1 诱导的伤害性行为可能是由脊髓中的 NMDA 受体介导的。
The most recently identified tachykinin, hemokinin-1, was cloned from mouse bone marrow. While several studies indicated that hemokinin-1 is involved in pain and inflammation, the physiological functions of hemokinin-1 are not fully understood. Our previous research demonstrated that the intrathecal (i.t.) administration of hemokinin-1 (0.00625–1.6 nmol) dose-dependently induced nociceptive behaviors, consisting of scratching, biting and licking in mice, which are very similar with the nociceptive behaviors induced by the i.t. administration of substance P. Low-dose (0.0125 nmol) hemokinin-1-induced nociceptive behavior was inhibited by a specific NK1receptor antagonist; however, high-dose (0.1 nmol) hemokinin-1-induced nociceptive behavior was not affected.In the present study, we found that the nociceptive behaviors induced by hemokinin-1 (0.1 nmol) were inhibited by the i.t. co-administration of MK-801 or D-APV, which are NMDA receptor antagonists. Moreover, we measured glutamate in the extracellular fluid of the mouse spinal cord using microdialysis. The i.t. administration of hemokinin-1 produced a significant increase in glutamate in the spinal cord, which was significantly reduced by co-administration with NMDA receptor antagonists. These results suggest that hemokinin-1-induced nociceptive behaviors may be mediated by the NMDA receptor in the spinal cord.