Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a mouse model.
Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a mouse model.
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腺苷酸环化酶抑制剂NB001对小鼠骨癌痛模型的镇痛作用
DOI：
10.1177/1744806916652409
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Zhao MG
中科院分区：
文献类型：
--
作者：
Kang WB;Yang Q;Guo YY;Wang L;Wang DS;Cheng Q;Li XM;Tang J;Zhao JN;Liu G;Zhuo M;Zhao MG
Background Cancer pain, especially the one caused by metastasis in bones, is a severe type of pain. Pain becomes chronic unless its causes and consequences are resolved. With improvements in cancer detection and survival among patients, pain has been considered as a great challenge because traditional therapies are partially effective in terms of providing relief. Cancer pain mechanisms are more poorly understood than neuropathic and inflammatory pain states. Chronic inflammatory pain and neuropathic pain are influenced by NB001, an adenylyl cyclase 1 (AC1)-specific inhibitor with analgesic effects. In this study, the analgesic effects of NB001 on cancer pain were evaluated. Results Pain was induced by injecting osteolytic murine sarcoma cell NCTC 2472 into the intramedullary cavity of the femur of mice. The mice injected with sarcoma cells for four weeks exhibited significant spontaneous pain behavior and mechanical allodynia. The continuous systemic application of NB001 (30 mg/kg, intraperitoneally, twice daily for three days) markedly decreased the number of spontaneous lifting but increased the mechanical paw withdrawal threshold. NB001 decreased the concentrations of cAMP and the levels of GluN2A, GluN2B, p-GluA1 (831), and p-GluA1 (845) in the anterior cingulate cortex, and inhibited the frequency of presynaptic neurotransmitter release in the anterior cingulate cortex of the mouse models. Conclusions NB001 may serve as a novel analgesic to treat bone cancer pain. Its analgesic effect is at least partially due to the inhibition of AC1 in anterior cingulate cortex.
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