Intrathecal injection of selected peptide Myr-RC-13 attenuates bone cancer pain by inhibiting KIF17 and NR2B expression

Pharmacol Biochem Behav. 2014 Jul:122:228-33. doi: 10.1016/j.pbb.2014.03.026. Epub 2014 Apr 12.

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.

Keywords: Cancer pain; Central sensitization; KIF17; Myr-RC-13; NR2B transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / complications
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Injections, Spinal
  • Kinesins / antagonists & inhibitors*
  • Kinesins / biosynthesis
  • Male
  • Mice
  • Mice, Inbred C3H
  • Myristic Acid / administration & dosage
  • Oligopeptides / administration & dosage
  • Oligopeptides / genetics
  • Pain / etiology
  • Pain / metabolism
  • Pain / prevention & control*
  • Pain Measurement / drug effects
  • Pain Measurement / methods
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / genetics
  • Random Allocation
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays / methods

Substances

  • KIF17 protein, mouse
  • NR2B NMDA receptor
  • Oligopeptides
  • Peptide Fragments
  • Receptors, N-Methyl-D-Aspartate
  • Myristic Acid
  • Kinesins