Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain.
Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain.
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DOI：
10.1097/j.pain.0000000000000514
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发表时间：
2016-06
期刊：
影响因子：
7.4
通讯作者：
Mantyh PW
中科院分区：
文献类型：
--
作者：
Guedon JG;Longo G;Majuta LA;Thomspon ML;Fealk MN;Mantyh PW
最近的研究表明，在具有显著骨骼疼痛的人类和动物中，可以检测到皮肤的机械超敏性的变化。然而，测量皮肤超敏反应的变化是否可以作为测量骨骼疼痛本身的可靠替代品仍不清楚。为了探讨这个问题，我们通过将GFP转染的NCTC 2472骨肉瘤细胞单侧注射和限制于C3H雄性小鼠的股骨来产生骨骼疼痛。从肿瘤注射后第7天开始，向动物施用媒介物、P2X3受体的抗体（抗P2X3）或抗NGF抗体。然后在肿瘤注射后第21、28和35天使用一系列骨骼疼痛相关行为和后爪足底表面上的机械超敏性的von Frey评估来测量疼痛和镇痛功效。用抗P2X3治疗的患有骨癌疼痛的动物显示皮肤超敏性降低，但骨骼疼痛行为没有减弱。然而，用抗NGF治疗的骨癌疼痛动物显示皮肤过敏和骨骼疼痛行为减少。这些结果表明，虽然骨癌可以诱导显着的骨骼疼痛相关的行为和皮肤的超敏反应，缓解皮肤的超敏反应并不总是伴随着骨骼疼痛的衰减。了解骨骼疼痛和皮肤疼痛之间的关系可以提供对疼痛如何处理和整合的洞察，并帮助定义骨骼疼痛的临床前测量，这些测量是临床试验的预测终点。
Recent studies have suggested that in humans and animals with significant skeletal pain, changes in the mechanical hypersensitivity of the skin can be detected. However, whether measuring changes in skin hypersensitivity can be a reliable surrogate for measuring skeletal pain itself remains unclear. To explore this question we generated skeletal pain by injecting and confining GFP-transfected NCTC 2472 osteosarcoma cells unilaterally to the femur of C3H male mice. Beginning at day 7 post-tumor injection, animals were administered vehicle, an antibody to the P2X3 receptor (anti-P2X3) or anti-NGF antibody. Pain and analgesic efficacy was then measured on days 21, 28 and 35 post-tumor injection using a battery of skeletal pain-related behaviors and von Frey assessment of mechanical hypersensitivity on the plantar surface of the hindpaw. Animals with bone cancer pain treated with anti-P2X3 showed a reduction in skin hypersensitivity but no attenuation of skeletal pain behaviors. Whereas animals with bone cancer pain treated with anti-NGF showed a reduction in both skin hypersensitivity and skeletal pain behaviors. These results suggest that while bone cancer can induce significant skeletal pain-related behaviors and hypersensitivity of the skin, relief of hypersensitivity of the skin is not always accompanied by attenuation of skeletal pain. Understanding the relationship between skeletal and skin pain may provide insight into how pain is processed and integrated and help define the preclinical measures of skeletal pain that are predictive endpoints for clinical trials.
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影响因子：
3.1
作者：
Andresen, Trine;Pfeiffer-Jensen, Mogens;Arendt-Nielsen, Lars
通讯作者：
Arendt-Nielsen, Lars
影响因子：
168.9
作者：
Christensen, Kaare;Doblhammer, Gabriele;Rau, Roland;Vaupel, James W.
通讯作者：
Vaupel, James W.
影响因子：
3.3
作者：
Castañeda-Corral G;Jimenez-Andrade JM;Bloom AP;Taylor RN;Mantyh WG;Kaczmarska MJ;Ghilardi JR;Mantyh PW
通讯作者：
Mantyh PW
影响因子：
3.7
作者：
Burston JJ;Sagar DR;Shao P;Bai M;King E;Brailsford L;Turner JM;Hathway GJ;Bennett AJ;Walsh DA;Kendall DA;Lichtman A;Chapman V
通讯作者：
Chapman V
影响因子：
7.4
作者：
Ambalavanar, R;Moritani, M;Dessem, D
通讯作者：
Dessem, D