No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex.

No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex.
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DOI:
10.1186/1756-6606-7-27
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发表时间:
2014-04-05
期刊:
影响因子:
3.6
通讯作者:
Zhuo M
Zhuo M
中科院分区:
医学3区
文献类型:
--
作者:
Liu MG;Zhuo M

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感觉系统中的瞬时受体电位香草酸1(TRPV 1)的研究的一个主要兴趣是它可能作为治疗慢性疼痛的药物靶点。虽然TRPV 1在外周伤害感受和致敏中的作用已被充分记录,但对其对疼痛相关的皮层可塑性的贡献知之甚少。在这里,我们使用64多电极阵列记录,以检查TRPV 1在两个主要形式的突触可塑性,长时程增强(LTP)和长时程抑制(LTD),在前扣带皮层(ACC)的潜在作用。我们发现,用[(E)-3-(4-叔丁基苯基)-N-(2,3-二氢苯并[B][1,4]二恶英-6-基)丙烯酰胺](AMG 9810,10 μM)或N-(3-甲氧基苯基)-4-氯肉桂酰胺(SB 366791,20 μM)药理学阻断TRPV 1未能影响成年小鼠ACC中强θ爆发刺激诱导的LTP。同样,AMG 9810和SB 366791均未阻断低频刺激诱导的扣带回LTD。对ACC不同层次的结果进行分析,得出了相同的结论。ACC网络中LTP或LTD显示通道的空间分布也未被TRPV 1拮抗剂改变。由于ACC中的皮质LTP和LTD在炎症或神经损伤引发的慢性疼痛中起关键作用,我们的研究结果表明TRPV 1可能不是治疗慢性疼痛的可行靶点,特别是在皮质水平。
One major interest in the study of transient receptor potential vanilloid type 1 (TRPV1) in sensory system is that it may serve as a drug target for treating chronic pain. While the roles of TRPV1 in peripheral nociception and sensitization have been well documented, less is known about its contribution to pain-related cortical plasticity. Here, we used 64 multi-electrode array recording to examine the potential role of TRPV1 in two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), in the anterior cingulate cortex (ACC). We found that pharmacological blockade of TRPV1 with either [(E)-3-(4-t-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide] (AMG9810, 10 μM) or N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791, 20 μM) failed to affect LTP induced by strong theta burst stimulation in the ACC of adult mice. Similarly, neither AMG9810 nor SB366791 blocked the cingulate LTD induced by low-frequency stimulation. Analysis of the results from different layers of the ACC obtained the same conclusions. Spatial distribution of LTP or LTD-showing channels among the ACC network was also unaltered by the TRPV1 antagonists. Since cortical LTP and LTD in the ACC play critical roles in chronic pain triggered by inflammation or nerve injury, our findings suggest that TRPV1 may not be a viable target for treating chronic pain, especially at the cortical level.
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