title: [Effects of intrathecal administration of AM22-52on mechanical allodynia and CCL2 expression in DRG in bone cancer rats].
abstract: The pain peptide adrenomedullin (AM) plays a pivotal role in pathological pain. The present study was designed to investigate the effect of blockade of AM receptor on bone cancer pain (BCP) and its mechanism. BCP was developed by inoculation of Walker 256 mammary gland carcinoma cells in the tibia medullary cavity of Sprague Dawley rats. The selective AM receptor antagonist AM22-52was administered intrathecally on 15 d after the inoculation. Quantitative real-time PCR was used to detect mRNA level of CC chemokine ligand 2 (CCL2) in dorsal root ganglion (DRG). Double immunofluorescence staining was used to analyze the localizations of CCL2 and AM in DRG of normal rats. The results showed that, from 6 to15 d after the inoculation, the animals showed significant reduction in the mechanical pain threshold in the ipsilateral hindpaw, companied by the decline in bone density of tibia bone. The expression of CCL2 mRNA in DRG of BCP rats was increased by 3 folds (P < 0.001 vs saline group). Intrathecal administration of AM22-52abolished bone cancer-induced mechanical allodynia and increase of CCL2 mRNA level (P < 0.001). In normal rats, CCL2 was co-localized with AM in DRG neurons. These results suggest that AM may play a role in the pathogenesis of BCP. The increased AM bioactivity up-regulates CCL2 expression in DRG, which may contribute to the induction of pain hypersensitivity in bone cancer.
authors.affiliation: College of Life Sciences, Fujian Normal University, Fujian Key Laboratory of Developmental Biology and Neuroscience, Fuzhou 350117, China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Fujian Normal University, Fujian Key Laboratory of Developmental Biology and Neuroscience, Fuzhou 350117, China.
authors.forename: Yuan-Hui
authors.initials: YH
authors.lastname: Huo
authors.affiliation: College of Life Sciences, Fujian Normal University, Fujian Key Laboratory of Developmental Biology and Neuroscience, Fuzhou 350117, China. yhong@fjnu.edu.cn.
authors.forename: Yanguo
authors.initials: Y
authors.lastname: Hong
mesh_terms: D053607:Adrenomedullin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy*; D018932:Chemokine CCL2 / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D058265:Receptors, Adrenomedullin / Q000037:antagonists & inhibitors
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D010446:Peptide Fragments; D058265:Receptors, Adrenomedullin; C104782:adrenomedullin (22-52); D053607:Adrenomedullin