Pan Ruirui, Di Huiting, Zhang Jinming, Huang Zhangxiang, Sun Yuming, Yu Weifeng, Wu Feixiang
Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China.
Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China ; Department of Anesthesiology, Kunming General Hospital of Chengdu Military Command, Yunnan 650032, China.
Mediators Inflamm. 2015;2015:523896. doi: 10.1155/2015/523896. Epub 2015 Oct 18.
Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-α and IL-1β in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain.
尽管科学家和临床医生都尚未完全了解骨癌疼痛，但研究表明，Toll样受体4（TLR4）在骨癌疼痛的病理疼痛状态的起始和/或维持中起重要作用。一种有前景的骨癌疼痛治疗方法是通过RNA干扰下调TLR4；然而，裸小干扰RNA（siRNA）在长期治疗中无效。为了配制一种可行的骨癌疼痛长期治疗方法，制备了一种可诱导的慢病毒LvOn-siTLR4（携带靶向TLR4的siRNA的四环素诱导慢病毒），并在通过向左腿注射Walker 256细胞诱导的骨癌疼痛大鼠中观察其镇痛作用。结果表明，鞘内注射LvOn-siTLR4并口服强力霉素（Dox）可有效减轻Walker 256细胞诱导的伤害感受，同时抑制TLR4的mRNA和蛋白表达。脊髓中的促炎细胞因子如TNF-α和IL-1β也减少。这些发现表明，TLR4可能是骨癌疼痛治疗的一个靶点，四环素诱导慢病毒LvOn-siTLR4代表了骨癌疼痛长期治疗的一种新的潜在选择。
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