Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development.
Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development.
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DOI：
10.1097/j.pain.0000000000001027
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发表时间：
2017-11
期刊：
影响因子：
7.4
通讯作者：
Hathway GJ
中科院分区：
文献类型：
--
作者：
Kwok CH;Devonshire IM;Imraish A;Greenspon CM;Lockwood S;Fielden C;Cooper A;Woodhams S;Sarmad S;Ortori CA;Barrett DA;Kendall D;Bennett AJ;Chapman V;Hathway GJ
补充数字内容可在正文中找到。在啮齿动物和人类的早期生活中，控制自上而下疼痛控制的脑干中心内的内源性大麻素信号都发生了显着变化。显著的年龄和经验依赖的脊髓和棘上神经网络的重构，导致早期生活中疼痛反应的改变。在成人中，存在调节疼痛反应的内源性阿片肽和内源性大麻素(ECs)疼痛控制系统，但它们在疼痛急性反应和出生后神经发育中所起的作用尚不清楚。在这里，我们研究了大鼠和人类脑干核团中内皮细胞的角色变化，这些核团对于控制从出生到成年的伤害性感受至关重要。利用体内电生理学，我们发现在中脑导水管周围灰质(PAG)和延髓轮状腹侧核(RVM)微量注射ECs受体激动剂和拮抗剂的效应发生了实质性的功能变化，这两个部位在成年后脊髓上控制疼痛和维持慢性疼痛状态中发挥着核心作用。我们发现，在未成熟的PAG和RVM中，孤儿受体GPR55能够介导成人所没有的深刻的镇痛作用。我们发现，PAG和RVM内的内源性大麻素类神经递质、花生胺和2-花生四烯基甘油的组织水平受发育调节(使用质谱学)。用定量聚合酶链式反应和免疫组织化学方法检测血管内皮细胞酶和受体的表达模式和水平。在人类脑干中，我们利用聚合酶链式反应和原位杂交法显示了涉及内皮细胞功能的关键酶和受体的表达随年龄的变化。这些数据表明，内皮细胞上的重大变化到目前为止还是未知的，这为允许正常、成熟的疼痛反应的复杂神经化学变化提供了新的线索。
Supplemental Digital Content is Available in the Text. Endocannabinoid signalling within brainstem centres that control top-down pain control changes significantly in early life in both rodents and humans. Significant age- and experience-dependent remodelling of spinal and supraspinal neural networks occur, resulting in altered pain responses in early life. In adults, endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses, but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here, we have studied the changing role of the ECs in the brainstem nuclei essential for the control of nociception from birth to adulthood in both rats and humans. Using in vivo electrophysiology, we show that substantial functional changes occur in the effect of microinjection of ECs receptor agonists and antagonists in the periaqueductal grey (PAG) and rostroventral medulla (RVM), both of which play central roles in the supraspinal control of pain and the maintenance of chronic pain states in adulthood. We show that in immature PAG and RVM, the orphan receptor, GPR55, is able to mediate profound analgesia which is absent in adults. We show that tissue levels of endocannabinoid neurotransmitters, anandamide and 2-arachidonoylglycerol, within the PAG and RVM are developmentally regulated (using mass spectrometry). The expression patterns and levels of ECs enzymes and receptors were assessed using quantitative PCR and immunohistochemistry. In human brainstem, we show age-related alterations in the expression of key enzymes and receptors involved in ECs function using PCR and in situ hybridisation. These data reveal that significant changes on ECs that to this point have been unknown and which shed new light into the complex neurochemical changes that permit normal, mature responses to pain.
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DOI：
10.1006/bbrc.1999.0254
发表时间：
1999-03-16
影响因子：
3.1
作者：
Bisogno, T;Berrendero, F;Di Marzo, V
通讯作者：
Di Marzo, V
DOI：
10.1073/pnas.96.14.7719
发表时间：
1999-07-06
影响因子：
11.1
作者：
Fitzgerald, M;Jennings, E
通讯作者：
Jennings, E
影响因子：
64.8
作者：
Calignano, A;La Rana, G;Piomelli, D
通讯作者：
Piomelli, D
影响因子：
4.7
作者：
Finn, DP;Jhaveri, MD;Chapman, V
通讯作者：
Chapman, V
影响因子：
3.6
作者：
Deliu, Elena;Sperow, Margaret;Abood, Mary E.
通讯作者：
Abood, Mary E.