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D1 型 resolvin 全身给药可减轻小鼠癌性骨痛:疼痛发展和镇痛过程中无性别依赖性。

Systemic administration of Resolvin D1 reduces cancer-induced bone pain in mice: Lack of sex dependency in pain development and analgesia.

机构信息

Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA.

出版信息

Cancer Med. 2024 Aug;13(15):e70077. doi: 10.1002/cam4.70077.

Abstract

AIMS

Bone cancer produces severe pain that is treated with opioids, but serious side effects limit opioid utilization. There is therefore a need to develop effective and safe non-opioid alternatives. The lipid mediator, Resolvin D1 (RvD1), could be a prospective candidate for cancer pain treatment. To assess RvD1 and other potential candidates, appropriate animal models that recapitulate clinical features must be used. Although several preclinical models of cancer pain have been developed, the influence of sex on the development of cancer pain and the effectiveness of RvD1 have not been studied.

RESULTS

Using a mouse model of fibrosarcoma growth in and around the calcaneus bone, we demonstrated that the mechanical hyperalgesia in the tumor-bearing hind paw develops independently of sex, except that it developed a little sooner in female mice. A single intravenous injection of RvD1 (0.001-10 μg/kg) decreased hyperalgesia in both sexes with similar potency (ED = 0.0015 μg/kg) and efficacy. Repeated daily administration of 10 μg/kg RvD1 prolonged the analgesic effect and completely abolished hyperalgesia. This was also independent of sex.

CONCLUSION

In this preclinical mouse model of bone cancer pain, the development of pain and the analgesic effectiveness of RvD1 are not influenced by sex.

摘要

目的

骨癌会引发剧烈疼痛,临床上常采用阿片类药物进行治疗,但此类药物严重的副作用限制了其应用。因此,我们需要开发有效且安全的非阿片类替代药物。脂质介质 RvD1 可能是癌症疼痛治疗的候选药物。为了评估 RvD1 和其他潜在的候选药物,必须使用能够重现临床特征的合适动物模型。尽管已经开发了几种癌症疼痛的临床前模型,但性别对癌症疼痛的发展以及 RvD1 的有效性的影响尚未得到研究。

结果

我们使用在跟骨内和周围生长纤维肉瘤的小鼠模型,证明了荷瘤后后肢的机械性痛觉过敏的发展与性别无关,但在雌性小鼠中发展得稍早一些。单次静脉注射 RvD1(0.001-10μg/kg)对雌雄小鼠的痛觉过敏均具有相似的效力(ED=0.0015μg/kg)和疗效。每日重复给予 10μg/kg 的 RvD1 可延长镇痛作用,并完全消除痛觉过敏。这也与性别无关。

结论

在这种骨癌疼痛的临床前小鼠模型中,疼痛的发展和 RvD1 的镇痛效果不受性别影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f53b/11299078/2042b1457e0c/CAM4-13-e70077-g003.jpg

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