Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.
Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.
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抑制组蛋白脱乙酰酶可减弱吗啡耐受并恢复 BCP 大鼠 DRG 中的 MOR 表达
DOI：
10.3389/fphar.2018.00509
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发表时间：
2018
影响因子：
5.6
通讯作者：
Dong YL
中科院分区：
文献类型：
--
作者：
He XT;Zhou KX;Zhao WJ;Zhang C;Deng JP;Chen FM;Gu ZX;Li YQ;Dong YL
骨癌痛（BCP）患者易产生吗啡耐受，严重阻碍了其临床应用.越来越多的证据表明，组蛋白去乙酰化酶（HDAC）调节阿片类药物持续暴露后的镇痛耐受。然而，HDAC是否在BCP的发病机制中有助于吗啡耐受仍然是未知的。在目前的研究中，我们探讨了在BCP的发病过程中，HDACs在吗啡耐受中的可能参与。胫骨肿瘤细胞接种（TCI）后，我们发现TCI后DRG中HDAC表达的增加与莫尔表达的减少呈负相关。吗啡单独给药后，TCI大鼠的缩足阈值（PWT）和最大可能效应百分比（MPE）迅速下降。与此相反，与单独使用吗啡相比，SAHA和吗啡的同时使用显著升高了TCI大鼠的PWT和MPE。此外，我们发现，SAHA管理显着升高莫尔的表达在TCI大鼠的背根神经节与吗啡治疗或不治疗。此外，在SAHA给药后，神经元中莫尔和HDAC 1共表达的TC1诱导的增加显著降低。这些结果表明，HDACs与BCP发病过程中DRG中莫尔的下调有关。使用SAHA抑制HDAC可用于减弱BCP中的吗啡耐受性。
The easily developed morphine tolerance in bone cancer pain (BCP) significantly hindered its clinical use. Increasing evidence suggests that histone deacetylases (HDACs) regulate analgesic tolerance subsequent to continuous opioid exposure. However, whether HDACs contribute to morphine tolerance in the pathogenesis of BCP is still unknown. In the current study, we explored the possible engagement of HDACs in morphine tolerance during the pathogenesis of BCP. After intra-tibia tumor cell inoculation (TCI), we found that the increased expression of HDACs was negatively correlated with the decreased expression of MOR in the DRG following TCI. The paw withdrawal threshold (PWT) and percentage maximum possible effects (MPEs) decreased rapidly in TCI rats when morphine was used alone. In contrast, the concomitant use of SAHA and morphine significantly elevated the PWT and MPEs of TCI rats compared to morphine alone. Additionally, we found that SAHA administration significantly elevated MOR expression in the DRG of TCI rats with or without morphine treatment. Moreover, the TCI-induced increase in the co-expression of MOR and HDAC1 in neurons was significantly decreased after SAHA administration. These results suggest that HDACs are correlated with the downregulation of MOR in the DRG during the pathogenesis of BCP. Inhibition of HDACs using SAHA can be used to attenuate morphine tolerance in BCP.
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影响因子：
25
作者：
Kim, Jin Young;Shen, Siming;Dietz, Karen;He, Ye;Howell, Owain;Reynolds, Richard;Casaccia, Patrizia
通讯作者：
Casaccia, Patrizia
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1073/pnas.96.14.7731
发表时间：
1999-07-06
影响因子：
11.1
作者：
Mayer, DJ;Mao, JR;Price, DD
通讯作者：
Price, DD
DOI：
10.1124/jpet.103.060582
发表时间：
2004-04-01
影响因子：
3.5
作者：
Rashid, MH;Inoue, M;Ueda, H
通讯作者：
Ueda, H
雷公藤甲素通过抑制脊髓胶质细胞HDACs上调对骨癌疼痛大鼠的镇痛作用
影响因子：
9.3
作者：
Hu XF;He XT;Zhou KX;Zhang C;Zhao WJ;Zhang T;Li JL;Deng JP;Dong YL
通讯作者：
Dong YL