Blockade of peripheral nociceptive signal input relieves the formation of spinal central sensitization and retains morphine efficacy in a neuropathic pain rat model
Blockade of peripheral nociceptive signal input relieves the formation of spinal central sensitization and retains morphine efficacy in a neuropathic pain rat model
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阻断外周伤害性信号输入可减轻脊髓中枢敏化的形成并保留吗啡在神经性疼痛大鼠模型中的功效
DOI：
10.1016/j.neulet.2019.134643
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发表时间：
2019-11
影响因子：
2.5
通讯作者：
Xu Tao
中科院分区：
文献类型：
--
作者：
Zhong Wenhui;Ma Xiaqing;Xing Yuna;Kim Dong Kwan;Wang Aizhong;Jiang Wei;Xu Tao
神经可塑性，尤其是中枢敏化，对于神经性疼痛的发生和维持至关重要。不幸的是，吗啡的镇痛效力在动物模型和患有神经性疼痛的患者中大大降低。我们假设激动剂或神经性疼痛对脊髓 N-甲基-d-天冬氨酸受体 (NMDAR) 的预激活促进了吗啡诱导的镇痛耐受的发展。因此，我们研究了神经性疼痛诱导的脊髓 NMDAR 激活对雄性 Sprague-Dawley 大鼠吗啡诱导的镇痛耐受性发展的影响。四天的慢性压迫性损伤 (CCI) 诱导脊髓 NR1 上调。一旦建立，脊髓中枢敏化就会加速吗啡引起的镇痛耐受的发展。持续输注罗哌卡因可防止 CCI 诱导的脊髓 P 物质 (SP)、NR1 和 TRPV1 增加。阻断外周伤害性输入可防止慢性吗啡引起的脊髓 SP、NR1 和 TRPV1 的增加以及 CCI 模型中吗啡剂量反应曲线的右移。这些发现表明脊髓 NMDAR 的预激活有助于中枢敏化并增强吗啡诱导的镇痛耐受的发展。在诱导阶段中断外周伤害性输入可以防止脊髓中枢敏化并保留吗啡功效，从而延迟神经病患者吗啡诱导的耐受性的发展。
Neural plasticity, especially central sensitization, is essential for developing and maintaining neuropathic pain. Unfortunately, the analgesic potency of morphine is greatly reduced in animal models and patients with neuropathic pain. We hypothesized that pre-activation of spinal N-methyl-d-aspartate receptors (NMDARs) by agonist or neuropathic pain facilitated the development of morphine-induced analgesic tolerance. We therefore investigated the effects of spinal NMDAR activation, induced by neuropathic pain, on the development of morphine-induced analgesic tolerance in male Sprague-Dawley rats. Four days of chronic constriction injury (CCI) induced upregulation of spinal NR1. Once established, spinal central sensitization accelerated the development of morphine-induced analgesic tolerance. Continuous ropivacaine infusion prevented CCI-induced increases in spinal Substance P (SP), NR1, and TRPV1. Blockade of peripheral nociceptive inputs prevented chronic morphine-induced increases in spinal SP, NR1, and TRPV1 and a rightward shift of the morphine dose-response curve in the CCI model. These findings suggest that pre-activation of spinal NMDARs contributes to central sensitization and potentiates the development of morphine-induced analgesic tolerance. Interruption of the peripheral nociceptive inputs during the induction phase could prevent spinal central sensitization and retain morphine efficacy, thereby delaying the development of morphine-induced tolerance in patients with neuropathic conditions.
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影响因子：
8.8
作者：
Roh, Dae-Hyun;Kim, Hyun-Woo;Lee, Jang-Hern
通讯作者：
Lee, Jang-Hern
DOI：
10.1111/j.1526-4637.2009.00588.x
发表时间：
2009-04
期刊：
Pain medicine (Malden, Mass.)
影响因子：
--
作者：
Yawn BP;Wollan PC;Weingarten TN;Watson JC;Hooten WM;Melton LJ 3rd
通讯作者：
Melton LJ 3rd
DOI：
10.1016/j.ejps.2016.03.019
发表时间：
2016-09
期刊：
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
影响因子：
--
作者：
W. Ochiai;M. Kaneta;Marina Nagae;Ami Yuzuhara;Xin Li;Haruka Suzuki;Mika Hanagata;S. Kitaoka;Wataru Suto;Yoshiki Kusunoki;R. Kon;Kazuhiko Miyashita;D. Masukawa;N. Ikarashi;M. Narita;Tsutomu Suzuki;K. Sugiyama
通讯作者：
W. Ochiai;M. Kaneta;Marina Nagae;Ami Yuzuhara;Xin Li;Haruka Suzuki;Mika Hanagata;S. Kitaoka;Wataru Suto;Yoshiki Kusunoki;R. Kon;Kazuhiko Miyashita;D. Masukawa;N. Ikarashi;M. Narita;Tsutomu Suzuki;K. Sugiyama
影响因子：
7.4
作者：
Charles A. Warwick;L. Shutov;A. Shepherd;D. Mohapatra;Y. Usachev
通讯作者：
Charles A. Warwick;L. Shutov;A. Shepherd;D. Mohapatra;Y. Usachev
影响因子：
16.6
作者：
Marrone MC;Morabito A;Giustizieri M;Chiurchiù V;Leuti A;Mattioli M;Marinelli S;Riganti L;Lombardi M;Murana E;Totaro A;Piomelli D;Ragozzino D;Oddi S;Maccarrone M;Verderio C;Marinelli S
通讯作者：
Marinelli S