SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain
SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain
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DOI：
10.1093/bja/aen347
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发表时间：
2009-02-01
影响因子：
9.8
通讯作者：
Namiki, A.
中科院分区：
文献类型：
--
作者：
Niiyama, Y.;Kawamata, T.;Namiki, A.
背景骨癌疼痛对癌症患者的生活质量有重大影响，但难以治疗。因此，需要开发一种新的骨癌疼痛策略来改善患者的生活质量。在这项研究中，我们研究了瞬时受体电位香草酸亚家族1（TRPV 1）拮抗剂和吗啡的组合对骨癌疼痛小鼠模型中疼痛相关行为的镇痛作用。将溶骨肉瘤细胞注射到C3 H/HeJ小鼠股骨的髓内空间中。研究了腹膜内吗啡的镇痛作用和TRPV 1拮抗剂SB 366791 [N-（3-甲氧基苯基）-4-氯肉桂酰胺]对骨癌疼痛相关行为的镇痛作用。观察SB 366791与吗啡合用对骨癌痛的镇痛作用。腹腔注射吗啡仅在最高剂量10 mg kg（-1）时显著减少了自发性退缩的次数，并改善了肩痛，而承重能力没有改善。腹腔注射SB 366791 0.3和1.0 mg/kg（-1），但0.1 mg/kg（-1）的剂量不能减少自发性退缩的次数，而承重和截肢均未改善。与吗啡单独给药相比，在吗啡基础上加入亚镇痛剂量的SB 366791（0.1 mg kg 21）可显著减少退缩次数，改善负重。我们的研究结果表明，吗啡和SB 366791的组合对骨癌疼痛具有有效的镇痛作用。这项研究的结果可能会导致骨癌疼痛治疗的新策略。
Background. Bone cancer pain has a major impact on the quality of life of cancer patients but is difficult to treat. Therefore, development of a novel strategy for bone cancer pain is needed for improvement of the patient quality of life. In this study, we examined the analgesic effects of the combination of a transient receptor potential vanilloid subfamily 1 (TRPV1) antagonist and morphine on pain-related behaviours in a murine model of bone cancer pain.Methods. C3H/HeJ mice underwent injection of osteolytic sarcoma cells into the intramedullary space of the femur. The analgesic effects of intraperitoneal morphine and the analgesic effect of a TRPV1 antagonist, SB366791 [N-(3-methoxyphenyl)-4-chlorocinnamide], on bone cancer pain-related behaviours were examined. The analgesic effects of the combination of SB366791 and morphine on bone cancer pain were also examined.Results. Intraperitoneal morphine significantly reduced the number of spontaneous flinches and improved ambulation only at the highest dose of 10 mg kg(-1) whereas weight-bearing was not improved. Intraperitoneal SB366791 at doses of 0.3 and 1.0 mg kg(-1), but not at a dose of 0.1 mg kg(-1), reduced the number of spontaneous flinches, whereas neither weight-bearing nor ambulation was improved. Addition of a sub-analgesic dose of SB366791 (0.1 mg kg 21) to morphine significantly reduced the number of flinches and improved weight-bearing compared with the effects of morphine aloneConclusions. Our findings showed that the combination of morphine and SB366791 has potent analgesic effects on bone cancer pain. The findings of this study may lead to novel strategies for the treatment of bone cancer pain.