Intrathecal Injection of JWH015 Attenuates Remifentanil-Induced Postoperative Hyperalgesia by Inhibiting Activation of Spinal Glia in a Rat Model
Intrathecal Injection of JWH015 Attenuates Remifentanil-Induced Postoperative Hyperalgesia by Inhibiting Activation of Spinal Glia in a Rat Model
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鞘内注射 JWH015 通过抑制大鼠模型中脊髓胶质细胞的激活来减轻瑞芬太尼引起的术后痛觉过敏
DOI：
10.1213/ane.0000000000000146
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发表时间：
2014-04
影响因子：
5.7
通讯作者：
Xiaoping Gu
中科院分区：
文献类型：
--
作者：
Yue Liu;Xiaojie Liu;Zhengliang Ma;Xiaoping Gu
背景：神经胶质细胞包括大胶质细胞和小胶质细胞，与痛觉过敏和神经炎症有关。在这项研究中，我们使用选择性大麻素受体2型（CB 2）激动剂JWH 015研究瑞芬太尼诱导的术后痛觉过敏。方法：采用缩足机械痛阈和缩足热潜伏期实验，观察术后痛敏和鞘内注射JWH 015后的机械痛敏和热痛敏。我们采用免疫组化和免疫印迹法研究JWH 015对瑞芬太尼诱导的大鼠术后痛觉过敏后CB 2受体、NR 2B亚基、活化的胶质细胞和促炎细胞因子表达的影响。结果：术中输注瑞芬太尼可诱发术后痛觉过敏。胶质细胞被激活，几种基因的表达水平显著增加，包括白细胞介素6、肿瘤坏死因子、CB 2和在Tyr-1472磷酸化的NR 2B亚基（p-NR 2B）。鞘内注射JWH 015显著抑制胶质细胞活化，抑制白细胞介素6、肿瘤坏死因子和p-NR 2B的表达，并刺激CB 2的表达，从而减轻术后痛觉过敏。然而，这些现象在预先施用AM 630的组中被消除。结论：在瑞芬太尼致痛过程中，脊髓背角胶质细胞活化、促炎细胞因子的产生以及CB 2和p-NR 2B的表达明显增加。JWH 015预处理可以调节这些变化，这可能是JWH 015抗痛觉过敏作用的主要机制。
BACKGROUND:Hyperalgesia and neuroinflammation are associated with glia, which consists of macroglia and microglia. In this study, we used a selective cannabinoid receptor type 2 (CB2) agonist JWH015 to investigate remifentanil-induced postoperative hyperalgesia. METHODS:Mechanical allodynia and thermal hyperalgesia after postoperative hyperalgesia and intrathecal injection of JWH015 were assessed by the paw withdrawal mechanical threshold and paw withdrawal thermal latency tests. We used immunohistochemistry and immunoblotting to investigate the effect of JWH015 on CB2 receptor, NR2B subunits, activated glial cells, and proinflammatory cytokine expression in rats after remifentanil-induced postoperative hyperalgesia. RESULTS:Postoperative hyperalgesia was induced by intraoperative infusion of remifentanil. Glial cells were activated, and expression levels of several genes were significantly increased, including interleukin 6, tumor necrosis factor &agr;, CB2, and the NR2B subunit phosphorylated at Tyr-1472 (p-NR2B). Intrathecal injection of JWH015 significantly inhibited glial cell activation, suppressed expression of interleukin 6, tumor necrosis factor &agr;, and p-NR2B, and stimulated CB2 expression, thus attenuating postoperative hyperalgesia. However, these phenomena were abolished in the group that was preadministered with AM630. CONCLUSIONS:The activation of glia, the production of proinflammatory cytokines, and the expression of CB2 and p-NR2B in the spinal dorsal horn increase significantly during the process of remifentanil-induced hyperalgesia. These changes can be regulated by pretreatment with JWH015, which may be the main mechanism underlying the antihyperalgesia effects of JWH015.
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影响因子：
8.8
作者：
Guignard, B;Bossard, AE;Chauvin, M
通讯作者：
Chauvin, M
影响因子：
8.8
作者：
Joly, V;Richebe, P;Chauvin, M
通讯作者：
Chauvin, M
DOI：
10.1073/pnas.81.21.6890
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
FYFFE, REW;PERL, ER
通讯作者：
PERL, ER
DOI：
--
发表时间：
2005
期刊：
The EMBO journal
影响因子：
--
作者：
R. Sitcheran;P. Gupta;P. Fisher;A. Baldwin
通讯作者：
R. Sitcheran;P. Gupta;P. Fisher;A. Baldwin
影响因子：
6.2
作者：
Sheng, WS;Hu, SX;Peterson, PK
通讯作者：
Peterson, PK