PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.
PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.
复制标题
PLGA-苏蛋白减弱阿片类药物诱导的痛觉过敏，并抑制脊髓CAMKIIα。
DOI：
10.1371/journal.pone.0146393
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wang ZJ
中科院分区：
文献类型：
--
作者：
Hu X;Huang F;Szymusiak M;Tian X;Liu Y;Wang ZJ
阿片类药物诱导的痛觉过敏（OIH）是与长期使用阿片类药物治疗慢性疼痛相关的主要问题之一。缺乏对OIH的有效治疗。在这项研究中，我们研究了姜黄素在减轻OIH中的功效和初步机制。我们采用了一种新开发的PLGA-姜黄素纳米制剂（PLGA-姜黄素），以提高姜黄素的溶解度，这一直是正确表征姜黄素的作用机制和功效的主要障碍。我们发现，姜黄素鞘内或口服给药可显著减弱吗啡诱导的OIH小鼠的痛觉过敏。此外，我们证明姜黄素对OIH的影响与抑制慢性吗啡诱导的脊髓背角浅层CaMKIIα激活有关。这些数据表明，PLGA-姜黄素可能通过抑制CaMKIIα及其下游信号转导来逆转OIH。
Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin’s mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.