Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition.
Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition.
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DOI：
10.1016/j.neuroscience.2011.01.045
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发表时间：
2011-04-28
期刊：
影响因子：
3.3
通讯作者：
Ro, J. Y.
中科院分区：
文献类型：
--
作者：
Niu, K.;Saloman, J. L.;Zhang, Y.;Ro, J. Y.
在这项研究中，我们研究了ATP依赖性K+通道（KATP）的功能亚基是否在三叉神经节（TG）中表达，其中包含支配口腔和面部结构的感觉神经元。我们还研究了在急性口面肌肉疼痛的情况下，KATP的直接激活是否能有效减弱机械超敏反应。在年龄匹配的雄性和雌性Sprague道利大鼠中进行TG中KATP表达和行为学研究。RT-PCR实验表明，向内整流孔形成亚基，Kir6.1和Kir6.2，以及调节磺酰脲亚基，SUR 1和SUR 2，可靠地检测到在TG的mRNA。随后的蛋白质印迹分析证实了所有4个亚基的蛋白质在TG中表达，并显示Kir6.2在雄性TG中的表达水平显著高于雌性大鼠。这一观察结果证实了较高百分比的Kir 6阳性咬肌传入雌性大鼠的免疫组织化学演示。咬肌注射辣椒素引起咬肌对伤害性机械刺激敏感性的时间依赖性增加。一个特定的KATP激动剂，吡那地尔，剂量依赖性衰减辣椒素诱导的机械过敏性雄性大鼠。在雄性大鼠中完全阻断辣椒素反应的吡那地尔剂量（20µg）在雌性大鼠中无效，无论其发情期如何。只有在我们使用的最高剂量（300µg）下，吡那地尔对雌性大鼠部分有效。类似地，另一种KATP激动剂，靶向不同KATP亚基的二氮嗪也显示出减弱辣椒素诱导的咬肌过敏的性别特异性反应。这些数据表明，性别差异的功能性KATP的表达在TG可能是性别特异性反应KATP激动剂。本研究提供了新的信息性别差异KATP的表达在TG和口面部肌肉疼痛条件下的贡献。
In this study, we examined whether functional subunits of the ATP-dependent K+ channel (KATP) are expressed in trigeminal ganglia (TG), which contains sensory neurons that innervate oral and facial structures. We also investigated whether direct activation of the KATP effectively attenuates mechanical hypersensitivity in the context of an acute orofacial muscle pain condition. The KATP expression in TG and behavioral studies were conducted in age matched male and female Sprague Dawley rats. RT-PCR experiments showed that the mRNAs for the inwardly rectifying pore-forming subunits, Kir6.1 and Kir6.2, as well as the regulatory sulphonylurea subunits, SUR1 and SUR2, were reliably detected in TG. Subsequent western blot analysis confirmed that proteins for all 4 subunits are expressed in TG, and showed that Kir6.2 is expressed at a significantly higher level in male TG compared to that of female rats. This observation was confirmed by the immunohistochemical demonstration of higher percentages of Kir6 positive masseter afferents in female rats. Masseteric injection of capsaicin evokes a time dependent increase in masseter sensitivity to noxious mechanical stimulation. A specific KATP agonist, pinacidil, dose-dependently attenuated the capsaicin-induced mechanical hypersensitivity in male rats. The dose of pinacidil (20µg) that completely blocked the capsaicin responses in male rats was ineffective in female rats regardless of their estrus phases. Only at the highest dose (300µg) we used, pinacidil was partially effective in female rats. Similarly, another KATP agonist, diazoxide which targets different KATP subunits also showed sex specific responses in attenuating capsaicin-induced masseter hypersensitivity. These data suggested that sex differences in functional KATP expression in TG may underlie sex specific responses to KATP agonists. The present study provided novel information on sex differences in KATP expression in TG and its contribution under an orofacial muscle pain condition.
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影响因子：
56.9
作者：
AMOROSO, S;SCHMIDANTOMARCHI, H;LAZDUNSKI, M
通讯作者：
LAZDUNSKI, M
影响因子：
4.7
作者：
Granados-Soto, V;Argüelles, CF;Ortiz, MI
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Ortiz, MI
DOI：
10.1016/s0735-1097(02)01947-2
发表时间：
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影响因子：
24
作者：
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通讯作者：
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作者：
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通讯作者：
Sekiguchi, Fumiko
影响因子：
5
作者：
Ortiz, MI;Torres-López, JE;Granados-Soto, V
通讯作者：
Granados-Soto, V