A Single Intrathecal or Intraperitoneal Injection of CB2 Receptor Agonist Attenuates Bone Cancer Pain and Induces a Time-Dependent Modification of GRK2

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• 作者：Cui’e Lu ; Linyu Shi ; Bei Sun ; Yu Zhang ; Bailing Hou…
• 关键词：Spinal cord ; CB2 ; JWH ; 015 ; GRK2 ; Bone cancer pain
• 刊名：Cellular and Molecular Neurobiology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：37
• 期：1
• 页码：101-109
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Neurosciences; Cell Biology; Neurobiology;
• 出版者：Springer US
• ISSN：1573-6830
• 卷排序：37

文摘

The objective of this study was to explore the potential role of G-protein-coupled receptor kinase 2 (GRK2) in the progression of cannabinoid 2 receptor (CB2) agonist-induced analgesic effects of bone cancer pain. Female Sprague–Dawley rats, weighing 160–180 g, were utilized to establish a model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. JWH-015, a selective CB2 agonist, was injected intrathecally or intraperitoneally on postoperative day 10. Bone cancer-induced pain behaviors—mechanical allodynia and ambulatory pain—were assessed on postoperative days −1 (baseline), 4, 7, and 10 and at post-treatment hours 2, 6, 24, 48, and 72. The expressions of spinal CB2 and GRK2 protein were detected by Western Blotting on postoperative days −1 (baseline), 4, 7, and 10 and at post-treatment hours 6, 24, and 72. The procedure produced prolonged mechanical allodynia, ambulatory pain, and different changes in spinal CB2 and GRK2 expression levels. Intrathecal or intraperitoneal administration of JWH-015 alleviated the induced mechanical allodynia and ambulatory pain, and inhibited the downregulation of spinal GRK2 expression. These effects were in a time-dependent manner and reversed by pretreatment of CB2 selective antagonist AM630. The results affirmed CB2 receptor agonists might serve as new treatment targets for bone cancer pain. Moreover, spinal GRK2 was an important regulator of CB2 receptor agonist-analgesia pathway.