Selectins and integrins but not platelet-endothelial cell adhesion molecule-1 regulate opioid inhibition of inflammatory pain
Selectins and integrins but not platelet-endothelial cell adhesion molecule-1 regulate opioid inhibition of inflammatory pain
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DOI：
10.1038/sj.bjp.0705837
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发表时间：
2004-06-01
影响因子：
7.3
通讯作者：
Stein, C
中科院分区：
文献类型：
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作者：
Machelska, H;Brack, A;Stein, C
1炎症性疼痛的控制可以通过白细胞在应激（例如实验性游泳应激或手术）时分泌的阿片肽激活外周感觉神经上的阿片受体来实现。免疫细胞向损伤组织的外渗涉及通过血管壁的滚动、粘附和迁移，由各种粘附分子协调。2在这里，我们评估了选择素、整合素α（4）和β（2）以及血小板内皮细胞粘附分子-1（PECAM-1）对阿片类药物介导的炎性疼痛抑制的相对贡献。3我们使用流式细胞术，在由完全弗氏佐剂诱导的单侧后爪炎症的大鼠中进行双重免疫荧光和伤害感受（爪压力）测试。4在发炎组织中，43-58%的造血细胞（CD 45（+））表达阿片肽。分别有7%和98%的含阿片样物质的白细胞共表达L-选择素和β 2。α（4）整联蛋白在大多数白细胞中以低水平表达。含阿片样物质的细胞、血管P-和E-选择素以及PECAM-1同时上调。5游泳应激在发炎组织中产生有效的阿片样物质介导的抗伤害感受，不受PECAM-1阻断的影响。然而，用岩藻多糖阻断L-和P-选择素，或用单克隆抗体阻断α（4）和β（2）完全消除了外周应激诱导的抗伤害感受。这与含阿片样物质的白细胞向炎症组织迁移的40%减少相吻合。6这些发现确立了选择素和整合素α（4）和β（2），但不是PECAM-1，作为参与应激诱导的阿片样物质介导的炎症抗伤害感受的重要分子。他们指出，应用抗选择素、抗α（4）和抗β（2）策略的抗炎治疗应谨慎使用，因为它们可能会损害内在的疼痛抑制。英国药理学杂志（2004）。
1 Control of inflammatory pain can result from activation of opioid receptors on peripheral sensory nerves by opioid peptides secreted from leukocytes in response to stress (e.g. experimental swim stress or surgery). The extravasation of immunocytes to injured tissues involves rolling, adhesion and transmigration through the vessel wall, orchestrated by various adhesion molecules.2 Here we evaluate the relative contribution of selectins, integrins alpha(4) and beta(2), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) to the opioid-mediated inhibition of inflammatory pain.3 We use flow cytometry, double immunofluorescence and nociceptive (paw pressure) testing in rats with unilateral hind paw inflammation induced by complete Freund's adjuvant.4 In inflamed tissue, 43-58% of hematopoietic cells (CD45(+)) expressed opioid peptides. L-selectin and beta(2) were coexpressed by 7 and 98% of opioid-containing leukocytes, respectively. Alpha(4) integrin was expressed in low levels by the majority of leukocytes. Opioid-containing cells, vascular P- and E-selectin and PECAM-1 were simultaneously upregulated.5 Swim stress produced potent opioid-mediated antinociception in inflamed tissue, unaffected by blockade of PECAM-1. However, blockade of L- and P- selectins by fucoidin, or of alpha(4) and beta(2) by monoclonal antibodies completely abolished peripheral stress-induced antinociception. This coincided with a 40% decrease in the migration of opioid-containing leukocytes to inflamed tissue.6 These findings establish selectins and integrins alpha(4) and beta(2), but not PECAM-1, as important molecules involved in stress-induced opioid-mediated antinociception in inflammation. They point to a cautious use of anti-inflammatory treatments applying anti-selectin, anti-alpha(4) and anti-beta(2) strategies because they may impair intrinsic pain inhibition. British Journal of Pharmacology (2004).