title: Upregulation of P2X3 receptors by neuronal calcium sensor protein VILIP-1 in dorsal root ganglions contributes to the bone cancer pain in rats.
abstract: Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. In this study, we first demonstrated that a functional upregulation of P2X3 receptors in dorsal root ganglion (DRG) neurons is closely associated with the neuronal hyperexcitability and the cancer-induced bone pain in MRMT-1 tumor cell-inoculated rats. Second, we revealed that visinin-like protein 1 (VILIP-1), a member of visinin-like proteins that belong to the family of neuronal calcium sensor proteins is responsible for the observed upregulation of P2X3 receptors in DRG neurons. The interaction between the amino terminus of VLIP-1 and the carboxyl terminus of the P2X3 receptor is critical for the surface expression and functional enhancement of the receptor. Finally, overexpression of VILIP-1 increases the expression of functional P2X3 receptors and enhances the neuronal excitability in naive rat DRG neurons. In contrast, knockdown of VILIP-1 inhibits the development of bone cancer pain via downregulation of P2X3 receptors and repression of DRG excitability in MRMT-1 rats. Taken together, these results suggest that functional upregulation of P2X3 receptors by VILIP-1 in DRG neurons contributes to the development of cancer-induced bone pain in MRMT-1 rats. Hence, P2X3 receptors and VILIP-1 could serve as potential targets for therapeutic interventions in cancer patients for pain management. Pharmacological blockade of P2X3 receptors or knockdown of VILIP-1 in DRGs would be used as innovative strategies for the treatment of bone cancer pain.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, PR China Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China Key Laboratory for Neuroscience, Ministry of Education and Ministry of Health, Beijing, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Dong
authors.initials: D
authors.lastname: Fang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.forename: You
authors.initials: Y
authors.lastname: Wan
authors.forename: De-Hua
authors.initials: DH
authors.lastname: Chui
authors.forename: Ji-Sheng
authors.initials: JS
authors.lastname: Han
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Xing
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000150:complications; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051596:Neurocalcin / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D010636:Phenols / Q000627:therapeutic use; D011083:Polycyclic Compounds / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: C470346:A-317491; D000970:Antineoplastic Agents; D051596:Neurocalcin; D016900:Neurofilament Proteins; D010636:Phenols; D011083:Polycyclic Compounds; D058477:Receptors, Purinergic P2X3; C496689:Vsnl1 protein, mouse; C051774:neurofilament protein H; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate
keywords: Bone cancer pain; Dorsal root ganglion; Hyperexcitability; Neuronal calcium sensor protein VILIP-1; P2X3 receptors