Knockdown of TRPV2 channels in sensory neurons increases limb use and weight bearing but does not affect spontaneous flinching behavior in a mouse model of bone cancer
Knockdown of TRPV2 channels in sensory neurons increases limb use and weight bearing but does not affect spontaneous flinching behavior in a mouse model of bone cancer
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DOI：
10.1177/1744806918819942
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发表时间：
2018-12-24
期刊：
影响因子：
3.3
通讯作者：
Kawamata M
中科院分区：
文献类型：
--
作者：
Yamamoto K;Tanaka S;Fuseya S;Ishida T;Zhang H;Kawamata T;Kawamata M
骨癌疼痛是一种复杂的疼痛状态，涉及持续性疼痛和运动相关性疼痛，这被认为是由不同的机制引起的。瞬时受体电位香草酸亚家族1（TRPV1）参与持续性疼痛，但不参与运动相关性疼痛。本研究旨在探讨瞬时受体电位香草酸亚家族2（TRPV2）在骨癌疼痛中的作用。 用荧光金标记法观察了支配雄性小鼠股骨的腰背根神经节中TRPV1和TRPV2免疫反应阳性神经元的比例。从肉瘤注射到左股骨后第14天开始，连续三天向小鼠鞘内注射针对TRPV 2的小干扰RNA（siRNA）或乱序siRNA。在患有骨癌的小鼠中，定量自发退缩的数量以评估持续疼痛，并将肢体使用和负重评估为运动相关疼痛的指征。Western blotting检测背根神经节TRPV2蛋白表达的变化。我们还检查了鞘内施用针对TRPV2的siRNA或乱序siRNA对无肿瘤的正常小鼠的热敏感性和机械敏感性的影响。 在支配股骨的背根神经节中，TRPV1和TRPV2阳性神经元的比例分别为21%和22%。在肉瘤注射后第13天，荷瘤小鼠表现出自发退缩次数增加，肢体使用和承重受损。在第13天，背根神经节中的TRPV2蛋白水平与基线相当。与用乱序siRNA治疗的组相比，针对TRPV2的siRNA显著改善了肢体使用和负重，但不影响自发性退缩的数量。针对TRPV2的siRNA不影响正常小鼠的热或机械敏感性。 结果表明，TRPV2与骨癌小鼠的运动相关疼痛有关，但与持续疼痛无关。
Bone cancer pain is a complex pain state involving ongoing pain and movement-related pain, which are thought to be caused by different mechanisms. Transient receptor potential vanilloid subfamily 1 (TRPV1) is involved in ongoing pain but not movement-related pain. The purpose of this study was to investigate the role of transient receptor potential vanilloid subfamily 2 (TRPV2) in bone cancer pain. Proportions of TRPV1- and TRPV2-immunoreactive neurons in lumbar dorsal root ganglia innervating the femurs of male mice were examined by using Fluoro-Gold. Mice were intrathecally injected with small interfering RNA (siRNA) against TRPV2 or scrambled siRNA for three consecutive days from day 14 after sarcoma injection into the left femur. In the mice with bone cancer, the number of spontaneous flinches was quantified for assessment of ongoing pain, and limb use and weight bearing were assessed as indications of movement-related pain. Changes in TRPV2 protein levels in dorsal root ganglion were evaluated by Western blotting. We also examined the effects of intrathecal administration of siRNA against TRPV2 or scrambled siRNA on thermal and mechanical sensitivities in normal mice without tumors. The proportions of TRPV1-immunoreactive and TRPV2-immunoreactive neurons were 21% and 22% of neurons in dorsal root ganglia innervating the femur, respectively. Tumor-bearing mice exhibited an increased number of spontaneous flinches and impaired limb use and weight bearing at day 13 after sarcoma injection. TRPV2 protein level in dorsal root ganglia at day 13 was comparable to that at baseline. siRNA against TRPV2 significantly improved limb use and weight bearing but did not affect the number of spontaneous flinches compared to those in the group treated with scrambled siRNA. siRNA against TRPV2 did not affect thermal or mechanical sensitivity in normal mice. The results suggest that TRPV2 is involved in movement-related pain but not ongoing pain in mice with bone cancer.
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DOI：
10.1523/jneurosci.1384-09.2011
发表时间：
2011-08-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Park U;Vastani N;Guan Y;Raja SN;Koltzenburg M;Caterina MJ
通讯作者：
Caterina MJ
影响因子：
2.4
作者：
Kawarai Y;Suzuki M;Yoshino K;Inoue G;Orita S;Yamauchi K;Aoki Y;Ishikawa T;Miyagi M;Kamoda H;Kubota G;Sakuma Y;Oikawa Y;Inage K;Sainoh T;Sato J;Nakamura J;Takaso M;Toyone T;Takahashi K;Ohtori S
通讯作者：
Ohtori S
影响因子：
3.4
作者：
Ivanusic JJ
通讯作者：
Ivanusic JJ
影响因子：
9.8
作者：
Delaney, A.;Fleetwood-Walker, S. M.;Fallon, M.
通讯作者：
Fallon, M.
影响因子：
3.4
作者：
Ahluwalia, J;Rang, H;Nagy, I
通讯作者：
Nagy, I