SEARCH

SEARCH BY CITATION

Keywords:

  • antisense oligonucleotide;
  • calcium;
  • mechanical allodynia;
  • PGF;
  • PGF receptor;
  • spinal cord

Abstract

Prostaglandin F (PGF) binds to its receptor (FP) to increase the intracellular-free calcium concentration ([Ca2+]i) by coupling of FP with Gq protein. Spinal intrathecal administration of PGF to mouse induces touch-evoked pain (mechanical allodynia), in which capsaicin-insensitive primary afferent Aβ-fibres and N-methyl-d-aspartate receptor ɛ4 subunit are involved. FP in the spinal cord, however, was not well characterized. Here, we showed constitutive expression of FP mRNA in mouse spinal cord, and functionally characterized spinal FP-expressing cells which were involved in PGF-induced mechanical allodynia. The method for repetitive administration of oligodeoxyribonucleotides through tubing to conscious mice was established for mechanical allodynia evaluation. We identified an antisense oligodeoxyribonucleotide targeting FP mRNA, causing both disappearance of PGF-induced mechanical allodynia and decrease of FP mRNA. With saline-administered mice, PGF rapidly increased [Ca2+]i of the cells in the deeper layer of the dorsal horn. In contrast, when the FP antisense oligodeoxyribonucleotide was repeatedly administered, the population of PGF-responsive cells in the slices reduced, and PGF-induced [Ca2+]i increase of these cells diminished. These data strongly suggested that, in the dorsal horn of the spinal cord, there are the FP-expressing cells which are involved in PGF-induced mechanical allodynia.