title: A Single Intrathecal or Intraperitoneal Injection of CB2 Receptor Agonist Attenuates Bone Cancer Pain and Induces a Time-Dependent Modification of GRK2.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China.
authors.forename: Cui'e
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China.
authors.forename: Linyu
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China.
authors.forename: Bailing
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China.
authors.forename: Yu'e
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China. mazhengliang1964@nju.edu.cn.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008, Jiangsu, China. 13813996903@126.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000072716:Cancer Pain / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000096:biosynthesis*; D007211:Indoles / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; C402944:JHW 015
keywords: Bone cancer pain; CB2; GRK2; JWH-015; Spinal cord