title: Intrathecal injection of selected peptide Myr-RC-13 attenuates bone cancer pain by inhibiting KIF17 and NR2B expression.
abstract: Although bone cancer pain is a common intractable clinical symptom, its underlying mechanisms are still elusive. Accumulating evidence reveals that the N-methyl-D-aspartate (NMDA) receptor containing a 2B subunit (NR2B) in the spinal cord contributes to bone cancer pain. Our preliminary study demonstrated that intrathecal injection of fusion peptide Myr-RC-13 could disrupt spinal KIF17/mLin10 interaction, which is an essential component of KIF17-mediated NR2B transport. Here we report a means by infusion of the selected peptide Myr-RC-13 intrathecally to attenuate bone cancer pain. The results showed that inoculation of fibrosarcoma NCTC 2472 cells into the femur cavity of C3H/HeJ mice induced progressive bone cancer pain and resulted in up-regulation of KIF17 and NR2B in the spinal cord. In addition, repetitive spinal delivery of Myr-RC-13 relieved bone cancer-related mechanical allodynia and spontaneous pain behaviors, and down-regulated expression of spinal KIF17 and NR2B. Finally, our results demonstrated that selected peptide Myr-RC-13 was able to attenuate bone cancer pain via decreasing spinal KIF17 and NR2B expressions. Therefore, selected peptide Myr-RC-13 might be a potential analgesic strategy for bone cancer pain.
authors.affiliation: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Ni
authors.affiliation: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China.
authors.forename: Yu-e
authors.initials: YE
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China. Electronic address: xiaopinggu1@gmail.com.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China. Electronic address: mazhengliang1964@yahoo.com.cn.
authors.forename: Zheng-liang
authors.initials: ZL
authors.lastname: Ma
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D007278:Injections, Spinal; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019814:Myristic Acid / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage / Q000235:genetics; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C409642:KIF17 protein, mouse; C121001:NR2B NMDA receptor; D009842:Oligopeptides; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D019814:Myristic Acid; D016547:Kinesins
keywords: Cancer pain; Central sensitization; KIF17; Myr-RC-13; NR2B transport