Behavioural and morphological evidence for the involvement of glial cell activation in delta opioid receptor function: implications for the development of opioid tolerance.
Behavioural and morphological evidence for the involvement of glial cell activation in delta opioid receptor function: implications for the development of opioid tolerance.
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DOI：
10.1186/1744-8069-3-7
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发表时间：
2007-03-12
期刊：
影响因子：
3.3
通讯作者：
Cahill, Catherine M.
中科院分区：
文献类型：
--
作者：
Holdridge, Sarah V.;Armstrong, Stacey A.;Taylor, Anna M. W.;Cahill, Catherine M.
先前的研究表明，体内长期吗啡处理诱导δ阿片受体（δORs）从细胞内区室移位到神经元质膜，并且这种运输事件与受体的功能能力增加相关。这种现象背后的机制尚不清楚;然而，慢性吗啡治疗已被证明涉及脊髓胶质细胞的激活和肥大。在本研究中，我们研究了激活的胶质细胞是否可能与长期吗啡处理后观察到的δ OR介导的抗伤害感受增强有关。因此，用吗啡处理动物，伴随或不伴随给予丙戊茶碱，丙戊茶碱是一种神经胶质活化的抑制剂，其先前显示阻断吗啡抗伤害耐受性的发展。先前证明的吗啡方案启动δOR运输诱导脊髓背侧中星形胶质细胞和小胶质细胞的活化，如细胞体积和细胞表面积的显著增加所示。与先前的数据一致，吗啡处理的大鼠显示δ OR介导的抗伤害感受显著增强。同时脊髓给予丙戊茶碱和吗啡可显著减弱脊髓免疫反应以及吗啡诱导的δ OR介导的效应增强。这些结果补充了先前的报告，即胶质细胞活化有助于阿片类镇痛耐受的状态，也表明神经胶质细胞通讯可能部分负责吗啡治疗后δ OR介导的效应的功能能力改变。
Previous studies have demonstrated that prolonged morphine treatment in vivo induces the translocation of delta opioid receptors (δORs) from intracellular compartments to neuronal plasma membranes and this trafficking event is correlated with an increased functional competence of the receptor. The mechanism underlying this phenomenon is unknown; however chronic morphine treatment has been shown to involve the activation and hypertrophy of spinal glial cells. In the present study we have examined whether activated glia may be associated with the enhanced δOR-mediated antinociception observed following prolonged morphine treatment. Accordingly, animals were treated with morphine with or without concomitant administration of propentofylline, an inhibitor of glial activation that was previously shown to block the development of morphine antinociceptive tolerance. The morphine regimen previously demonstrated to initiate δOR trafficking induced the activation of both astrocytes and microglia in the dorsal spinal cord as indicated by a significant increase in cell volume and cell surface area. Consistent with previous data, morphine-treated rats displayed a significant augmentation in δOR-mediated antinociception. Concomitant spinal administration of propentofylline with morphine significantly attenuated the spinal immune response as well as the morphine-induced enhancement of δOR-mediated effects. These results complement previous reports that glial activation contributes to a state of opioid analgesic tolerance, and also suggest that neuro-glial communication is likely responsible in part for the altered functional competence in δOR-mediated effects following morphine treatment.
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影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
影响因子：
1.7
作者：
Ma, JY;Zhao, ZQ
通讯作者：
Zhao, ZQ
影响因子：
3.8
作者：
Kest, B;Lee, CE;Inturrisi, CE
通讯作者：
Inturrisi, CE
影响因子：
5.7
作者：
Lu, CH;Chao, PC;Wu, CT
通讯作者：
Wu, CT
DOI：
10.1073/pnas.89.9.3696
发表时间：
1992-05-01
影响因子：
11.1
作者：
MELCHIORRI, P;MARITATI, M;ERSPAMER, V
通讯作者：
ERSPAMER, V