Morphine and pain-related stimuli enhance cell surface availability of somatic δ-opioid receptors in rat dorsal root ganglia
Morphine and pain-related stimuli enhance cell surface availability of somatic δ-opioid receptors in rat dorsal root ganglia
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DOI：
10.1523/jneurosci.3598-05.2006
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发表时间：
2006-01-18
影响因子：
5.3
通讯作者：
Beaudet, A
中科院分区：
文献类型：
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作者：
Gendron, L;Lucido, AL;Beaudet, A
本研究表明，大鼠背根神经节 (DRG) 神经元中的核周 δ-阿片受体 (δ OR) 结合并内在化脑脊液中循环的阿片配体。使用共聚焦和电子显微镜，我们发现长时间的吗啡处理增加了这些核周δOR的细胞表面密度，从而导致所有三种类型的DRG神经元（小、中和大）中荧光deltorphin（DLT）类似物omega-Bodipy 576/589 deltorphin-I 5-氨基戊酰胺（Fluo-DLT）的受体介导的内化。相比之下，将完全弗氏佐剂（CFA）注射到一只后爪中引起的慢性炎症疼痛选择性地增加了炎症同侧的中小型DRG神经元中的Fluo-DLT内化。根据我们之前对 mu-阿片受体 (mu OR) 敲除小鼠脊髓的研究，可以假设持续吗啡后观察到的 delta ORs 膜募集增强可归因于 mu ORs 的刺激。然而，炎性疼痛引起的效应的选择性表明它涉及不同的机制，即 C 和 A δ 纤维的模式特异性和疼痛相关激活。事实上，辣椒素对瞬时受体潜在香草酸1受体（由小直径（<600μm（2））DRG神经元选择性表达）的刺激，仅在该细胞群中增加了Fluo-DLT内化。因此，目前的结果表明，DRG 神经元表达 CSF 循环配体可接近的核周 delta OR，并且这些受体的密度以及因此可能的反应性可能受到疼痛相关刺激和持续暴露于 mu OR 激动剂的调节。
The present study demonstrates that perikaryal delta-opioid receptors (delta ORs) in rat dorsal root ganglion (DRG) neurons bind and internalize opioid ligands circulating in the CSF. Using confocal and electron microscopy, we found that prolonged morphine treatment increased the cell surface density of these perikaryal delta ORs and, by way of consequence, receptor-mediated internalization of the fluorescent deltorphin (DLT) analog omega-Bodipy 576/589 deltorphin-I 5-aminopentylamide (Fluo-DLT) in all three types of DRG neurons ( small, medium, and large). In contrast, chronic inflammatory pain induced by the injection of complete Freund's adjuvant (CFA) into one hindpaw selectively increased Fluo-DLT internalization in small and medium-sized DRG neurons ipsilateral to the inflammation. Based on our previous studies in the spinal cord of mu-opioid receptor (mu OR) knock-out mice, it may be assumed that the enhanced membrane recruitment of delta ORs observed after sustained morphine is attributable to stimulation of mu ORs. However, the selectivity of the effect induced by inflammatory pain suggests that it involves a different mechanism, namely a modality-specific and pain-related activation of C and A delta fibers. Indeed, stimulation by capsaicin of transient receptor potential vanilloid 1 receptors, which are selectively expressed by small diameter ( < 600 mu m(2)) DRG neurons, increased Fluo-DLT internalization exclusively in this cell population. The present results, therefore, demonstrate that DRG neurons express perikaryal delta ORs accessible to CSF-circulating ligands and that the density and, hence, presumably also the responsiveness, of these receptors may be modulated by both pain-related stimuli and sustained exposure to mu OR agonists.