The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats.
The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats.
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DOI：
10.1186/1744-8069-7-7
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发表时间：
2011-01-17
期刊：
影响因子：
3.3
通讯作者：
Maione S
中科院分区：
文献类型：
--
作者：
de Novellis V;Vita D;Gatta L;Luongo L;Bellini G;De Chiaro M;Marabese I;Siniscalco D;Boccella S;Piscitelli F;Di Marzo V;Palazzo E;Rossi F;Maione S
神经病理性疼痛是一种慢性疾病，由“疼痛基质”内的功能障碍引起。杏仁基底外侧核(BLA)可以调节皮质功能，该结构与内侧前额叶皮质(MPFC)之间的相互作用对于整合情绪显著信息是重要的。在本研究中，我们研究了瞬时受体电位香草素样蛋白1(TRPV1)和分解代谢酶脂肪酸酰胺水解酶(FAAH)在神经病大鼠边缘前/边缘下(PL/IL)皮质的形态功能变化中的作用。本实验观察了FAAH抑制剂和TPRV1通道拮抗剂N-花生四烯酰基-5-羟色胺(AA-5-HT)对神经病理性疼痛相关的伤害性行为的影响以及对PL/IL皮质锥体神经元表型的影响。通过电刺激BLA和施加后爪感觉前刺激，这些神经元被鉴定为属于BLA-mPFC通路。在假手术或备用神经损伤(SNI)大鼠中，观察AA-5-羟色胺(AA-5-HT)重复治疗前后大鼠自发活动和诱发活动的变化。与SNI诱导的PL/IL皮质神经元发生深刻表型重组的改变一致，表明mPFC神经元兴奋性和抑制性反应严重失衡，我们发现SNI大鼠PL/IL皮质细胞外谷氨酸水平升高，FAAH和TRPV1表达上调。每天使用AA-5-羟色胺治疗可恢复皮质神经元的活动，使与坐骨神经周围损伤相关的电生理变化正常化。最后，单次急性PL/IL皮质内微量注射AA-5-HT比URB597或I-RTX(选择性FAAH抑制剂或TRPV1阻滞剂)更有效地减轻痛觉异常。这些数据表明，血管内毒素可能参与了与周围神经损伤相关的皮质可塑性变化，并表明能够使血管内毒素传递正常化的治疗方法可能被证明在改善与神经病理性疼痛相关的症状和中枢后遗症方面有用。
Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats. The effect of N-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. These data suggest a possible involvement of endovanilloids in the cortical plastic changes associated with peripheral nerve injury and indicate that therapies able to normalize endovanilloid transmission may prove useful in ameliorating the symptoms and central sequelae associated with neuropathic pain.
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影响因子：
25
作者：
Cruikshank, Scott J.;Lewis, Timothy J.;Connors, Barry W.
通讯作者：
Connors, Barry W.
影响因子：
2.9
作者：
Borckardt, Jeffrey J.;Smith, Arthur R.;George, Mark S.
通讯作者：
George, Mark S.
影响因子：
3.6
作者：
Calejesan, AA;Kim, SJ;Zhuo, M
通讯作者：
Zhuo, M
影响因子：
5.3
作者：
Apkarian, AV;Sosa, Y;Gitelman, DR
通讯作者：
Gitelman, DR
影响因子：
5.3
作者：
Baliki, Marwan N.;Chialvo, Dante R.;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania