Studies for diversity of modulation system on Pain and Capsaicin sensitivities

疼痛和辣椒素敏感性调节系统多样性的研究

• 批准号: 16300138
• 负责人: KOIDE Tsuyoshi
• 金额: $ 9.6万
• 依托单位: National Institute of Genetics
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300138/
• 关键词: Pain; Capsaicin; TRP-V1; Mouse; Congenic strains; Thermo sensitivity

In animal, heat stimulation is transmitted to central nervous system (CNS) via sensory neuron, and is recognized as heat or pain. Various levels of heat sensations activate the multi functional pain receptors, TRPV channels that expressed in sensory ganglia. Many behavioral tests had been established to measure the pain sensitivity in rodents by investigating behavioral response from the aversive pain stimuli. Hot plate test displays the ability of pain recognition system or analgesic system based on upper CNS. The tail flick test displays the pain sensitivity based on nociceptive reflex. In the present study, we conducted QTL analyses to characterize genetic loci involved in the different sensitivity to heat evoked pain between two mouse strains, C57BL/6 and KJR. In the study, we applied hot plate test and tail flick test to assess the two types of pain sensitivity of BKF2 progeny generated form F1 progeny of C57BL/6 and KJR. In the analyses, we detected three significant loci for hot … More plate test, Hpq1, Hpq2 and Hpq3 and two significant loci for tail flick test, Tfq1 and Tfq2. The pain associated quantitative traits loci, Hpq1, Hpq2, Hpq3, Tfq1, and Tfq2 were located on the chromosomes, 2,10,18,8 and 10, respectively. Hpq2 and Tfq1 were overlapped on the same region of chromosome 10. These data suggested that genetic mechanism for strain difference of pain sensitivities between C57BL/6 and KJR that mediated by upper CNS and reflection system are mostly different but partly shared.To elucidate phenotype of thermo-sensation, we conducted recording of femoral nerve activity in vivo and intracellular free calcium (iCa) response to heat in vitro in mice of KJR. KJR is the mice strain known to be resistant to hot-plate test. Increment in neuronal activity from 25 C to 40 C was not different in KJR compared to the control. Whereas that from 25 C to 50 C was was different in KJR, when the degree of the increment was compared with C57BL/6 by two-way ANOVA. DRG neurons were isolated from these mice and iCa was measured by ratio methods with fluo-3 and fura-red. Surprisingly, all of the phenotypes including capsaicin resistance in KJR are not reproduced in isolated DRG neurons : We observed rise in iCa in some DRG neurons of KJR to heat and capsaicin. These results may suggest that thermo-sensation is a complicated sensory process involving contribution of proteins other than TRP channels and that the experiments in vitro and in vivo are needed to substantiate the phenotype. Less

在动物中，热刺激通过感觉神经元传播到中枢神经系统（CNS），并被认为是热或疼痛。各种水平的热感觉激活了在感觉神经节中表达的多功能疼痛受体。已经建立了许多行为测试，以通过研究厌恶性疼痛刺激的行为反应来测量啮齿动物的疼痛敏感性。热板测试显示基于上CNS的疼痛识别系统或镇痛系统的能力。尾部轻弹测试显示基于伤害感受反射的疼痛敏感性。在本研究中，我们进行了QTL分析，以表征与两种小鼠菌株C57BL/6和KJR之间对热诱发疼痛的不同敏感性有关的遗传位置。在研究中，我们应用了热板测试和尾部轻弹测试，以评估BKF2后代产生的两种类型的疼痛敏感性，形成了C57BL/6和KJR的F1后代。在分析中，我们检测到了三个重要的基因座，用于热板测试，HPQ1，HPQ2和HPQ3，以及两个重要的基因座，用于尾部轻弹测试，TFQ1和TFQ2。疼痛相关的定量性状基因座，HPQ1，HPQ2，HPQ3，TFQ1和TFQ2分别位于染色体上，分别为2,10,18,8和10。 HPQ2和TFQ1被重叠在染色体10的同一区域。这些数据表明，C57BL/6和KJR之间因CNS和反射系统介导的疼痛敏感性的应变差异的遗传机制主要是不同的，但部分共享但部分共享。 KJR小鼠的体外体外。 KJR是已知对热板测试具有抗性的小鼠菌株。与对照相比，KJR的神经元活性从25 C到40 C的增加没有差异。而在KJR中，从25 C到50 C则不同，而将增量的度量与C57BL/6的双向ANOVA进行比较时。从这些小鼠中分离出DRG神经元，并通过fluo-3和fura-red的比率方法测量ICA。令人惊讶的是，在孤立的DRG神经元中，没有再现包括KJR中辣椒素耐药性在内的所有表型：我们观察到ICA中的某些KJR的DRG神经元中的ICA上升至热和辣椒素。这些结果可能表明，热敏化是一个复杂的感觉过程，涉及TRP通道以外的蛋白质的贡献，并且需要体外和体内实验来证实表型。较少的

项目成果

Monoallelic yet combinatorial expression of variable exons of the protocadherin- a gene cluster in single neurons

原钙粘蛋白基因簇可变外显子在单个神经元中的单等位基因和组合表达

• 发表时间: 2005
• 期刊: Nature Genetics 37
• 作者: Ogasawara;M.;Imanishi;T.;Moriwaki;K.;Gaudieri;S.;Tsuda;H.;Hashimoto;H.;Shiroishi;T.;Gojobori;T.;Koide;T.;Esumi et al.
• 通讯作者: Esumi et al.

Molecular evolution of Cadherin-related neuronal receptor/protocadherin ・(CNR/Pcdh・) gene cluster in Mus musculus subspecies

小家鼠亚种钙粘蛋白相关神经元受体/原钙粘蛋白·(CNR/Pcdh·)基因簇的分子进化

• 期刊: Mol.Biol.Evol. (In press)
• 作者: Ogasawara;M.;Imanishi;T.;Moriwaki;K.;Gaudieri;S.;Tsuda;H.;Hashimoto;H.;Shiroishi;T.;Gojobori;T.;Koide;T.;Esumi et al.;Taguchi et al.
• 通讯作者: Taguchi et al.

カプサイシン受容体の活性調節剤、及びそれを用いた医薬組成物

辣椒素受体活性调节剂及使用其的药物组合物

• 发表时间: 2005