Leptin enhances NMDA-induced spinal excitation in rats: A functional link between adipocytokine and neuropathic pain
Leptin enhances NMDA-induced spinal excitation in rats: A functional link between adipocytokine and neuropathic pain
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瘦素增强 NMDA 诱导的大鼠脊髓兴奋：脂肪细胞因子与神经性疼痛之间的功能联系
DOI：
10.1016/j.pain.2011.01.054
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发表时间：
2011-06-01
期刊：
影响因子：
7.4
通讯作者：
Mao, Jianren
中科院分区：
文献类型：
--
作者：
Tian, Yinghong;Wang, Shuxing;Mao, Jianren
近年来的研究表明，瘦素（leptin，一种脂肪细胞因子）在神经损伤诱导的伤害性行为中起重要作用，但其细胞机制尚不清楚。采用大鼠脊髓薄片全细胞膜片钳记录技术，我们发现脊髓薄片灌流瘦素可剂量依赖性地增强脊髓II层神经元N-甲基-D-天冬氨酸（NMDA）受体介导的电流。在细胞水平上，瘦素对脊髓NMDA诱导电流的影响是通过瘦素受体和JAK 2/STAT 3（而不是PI 3 K或MAPK）途径介导的，因为瘦素效应在瘦素受体缺陷（db/db）小鼠中被消除，并被JAK/STAT抑制剂抑制。此外，我们证明了在幼稚大鼠，一个单一的鞘内注射瘦素增强自发咬，抓，舔行为引起的鞘内NMDA和重复鞘内注射瘦素引起热痛觉过敏和机械异常性疼痛，这是衰减的非竞争性NMDA受体拮抗剂MK-801。鞘内注射瘦素还上调大鼠脊髓背角内NMDA受体和pSTAT 3的表达，鞘内注射MK-801也减弱了瘦素的这种作用。我们的数据表明，瘦素和NMDA受体介导的脊髓神经元兴奋和它的功能作用在伤害性行为之间的关系。由于瘦素有助于神经损伤诱导的伤害性行为，因此本研究结果表明瘦素的脊髓效应与神经性疼痛的NMDA受体介导的细胞机制之间存在重要的细胞联系。(C)2011年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Recent studies have shown that leptin (an adipocytokine) played an important role in nociceptive behavior induced by nerve injury, but the cellular mechanism of this action remains unclear. Using the whole-cell patch-clamp recording from rat's spinal cord slices, we showed that superfusion of leptin onto spinal cord slices dose-dependently enhanced N-methyl-D-aspartate (NMDA) receptor-mediated currents in spinal cord lamina II neurons. At the cellular level, the effect of leptin on spinal NMDA-induced currents was mediated through the leptin receptor and the JAK2/STAT3 (but not PI3K or MAPK) pathway, as the leptin effect was abolished in leptin receptor-deficient (db/db) mice and inhibited by a JAK/STAT inhibitor. Moreover, we demonstrated in naive rats that a single intrathecal administration of leptin enhanced spontaneous biting, scratching, and licking behavior induced by intrathecal NMDA and that repeated intrathecal administration of leptin elicited thermal hyperalgesia and mechanical allodynia, which was attenuated by the noncompetitive NMDA receptor antagonist MK-801. Intrathecal leptin also upregulated the expression of NMDA receptors and pSTAT3 within the rat's spinal cord dorsal horn, and intrathecal MK-801 attenuated this leptin effect as well. Our data demonstrate a relationship between leptin and NMDA receptor-mediated spinal neuronal excitation and its functional role in nociceptive behavior. Since leptin contributes to nociceptive behavior induced by nerve injury, the present findings suggest an important cellular link between the leptin's spinal effect and the NMDA receptor-mediated cellular mechanism of neuropathic pain. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.