Kinin B1 receptors contributes to acute pain following minor surgery in humans.
Kinin B1 receptors contributes to acute pain following minor surgery in humans.
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DOI：
10.1186/1744-8069-6-12
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发表时间：
2010-02-13
期刊：
影响因子：
3.3
通讯作者：
Dionne RA
中科院分区：
文献类型：
--
作者：
Hamza M;Wang XM;Adam A;Brahim JS;Rowan JS;Carmona GN;Dionne RA
激肽通过激活两种类型的G蛋白偶联受体，激肽B1和B2受体，在组织损伤和炎症后的疼痛和痛觉过敏的调节中发挥重要作用。通常认为B2受体是组成型表达的，而B1受体是在炎症反应中诱导的。然而，很少有人知道激肽受体对急性炎症和炎症性疼痛的发病的调节作用。本研究探讨了组织损伤后早期激肽受体基因表达及其内源性配体水平的变化及其与临床疼痛的关系，以及COX抑制对其表达水平的影响。组织损伤导致术后3小时（急性炎症性疼痛开始）B1和B2受体基因表达显着上调。有趣的是，B1和B2受体基因表达的上调仅在酮咯酸治疗后与疼痛强度呈正相关，这表明在炎症疼痛过程中，胰高血糖素和激肽之间存在相互作用。此外，B1和B2受体的基因表达是相关的。组织损伤后，安慰剂和酮咯酸治疗组中第3小时的B1配体des-Arg 9-BK和des-Arg 10-KD均显著低于前2小时，但组间无显著差异。组织损伤也导致TRPV 1基因表达在术后3小时下调，酮咯酸治疗无显著影响。有趣的是，TRPV 1基因表达的变化与B1受体基因表达的变化相关，但与B2受体无关。这些结果在组织损伤的临床模型中提供了转录水平的证据，即激肽受体的上调参与了炎症和炎性疼痛的早期发展。B1受体的上调可能通过TRPV 1的激活而导致急性炎症性疼痛。
Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B1 receptors may contribute to acute inflammatory pain through TRPV1 activation.
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