Mechanisms of antinociception of spinal galanin: how does galanin inhibit spinal sensitization?
Mechanisms of antinociception of spinal galanin: how does galanin inhibit spinal sensitization?
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DOI：
10.1016/j.npep.2004.12.024
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发表时间：
2005-06-01
期刊：
影响因子：
2.9
通讯作者：
Yaksh, TL
中科院分区：
文献类型：
--
作者：
Hua, XY;Salgado, KF;Yaksh, TL
甘丙肽通过脊髓作用已被证明具有抗痛觉过敏作用。因此，在具有腰椎鞘内（IT）导管的大鼠中，通过IT递送甘丙肽（1-29）（Gal（1 - 29））和甘丙肽（2-11）（Gal（2 - 11））阻断由角叉菜胶爪注射诱发的热痛觉过敏，活性的等级顺序为Gal（1-29）> Gal（2-11）。我们试图确定这种脊髓作用是否反映了对传入递质释放的影响，P物质（SP）和/或次级神经元上，例如，神经激肽1（NK 1）受体激活的突触后信号传导。为了解决传入释放的问题，我们研究了IT管理甘丙肽对组织损伤诱导的脊髓NK 1内化（SP释放的指标）的影响。伤害刺激（爪压迫）引起背角板I中NK 1内化的增加。用Gal（1-29）和Gal（2-11）预处理大鼠可显著减弱诱发的NK 1内化，其活性顺序为Gal（1-29）> Gal（2-11）>生理盐水。为了解决突触后作用的问题，我们研究了IT甘丙肽对IT SP诱导的热痛觉过敏和脊髓PGE（2）释放的影响。将SP（30 nmol）直接应用于脊髓导致热阈值降低和脊髓透析液中PGE（2）浓度显著增加。Gal（1-29）和Gal（2-11）（10 nmol，IT）可逆转上述两种现象。这些发现表明，脊髓甘丙肽的抗痛觉过敏作用是由于其对初级传入神经的突触前（抑制SP释放）和突触后（阻断SP诱发的痛觉过敏和PGE（2）产生）部位的作用。(c)2005爱思唯尔有限公司保留所有权利。
Galanin by a spinal action has been shown to have an antihyperalgesic action. Thus, in rats with lumbar intrathecal (IT) catheters, the thermal hyperalgesia evoked by carrageenan paw injection was blocked by IT delivery of galanin(1-29) (Gal(1-29)) and galanin(2-11) (Gal(2-11)) with the rank order of activity being Gal(1-29) > Gal(2-11). We sought to determine whether this spinal action reflects an effect upon afferent transmitter release, e.g., substance P (SP), and/or on secondary neurons, e.g., signaling postsynaptic to neurokinin 1 (NK1) receptor activation. To address the question on afferent release, we investigated the effect of IT administration of galanin on tissue injury-induced spinal NK1 internalization (an indicator of SP release). Noxious stimulation (paw compression) produced an increase in NK1 internalization in dorsal horn lamina I. IT pretreatment of rats with Gal(1-29) and Gal(2-11) significantly attenuated the evoked NK1 internalization, with the rank order of activity being Gal(1-29) > Gal(2-11) > saline. To address the question of postsynaptic action, we examined the effects of IT galanin upon IT SP-induced thermal hyperalgesia and spinal PGE(2) release. Application of SP (30 nmol) directly to spinal cord led to a decrease in thermal thresholds and a profound increase in PGE(2) concentration in spinal dialysates. Both phenomena were reversed by Gal(1-29) and Gal(2-11) (10 nmol, IT). These findings suggest that the antihyperalgesic effect of spinal galanin is due to its action on sites both presynaptic (inhibition of SP release) and postsynaptic (blockade of SP-evoked hyperalgesia and PGE(2) production) to the primary afferents. (c) 2005 Elsevier Ltd. All rights reserved.