Functional characterization of prostaglandin F_2α receptor in the spinal cord for tactile pain (allodynia)

Prostaglandin F_2α (PGF_2α) binds to its receptor (FP) to increase the intracellular-free calcium concentration ([Ca²⁺]i) by coupling of FP with G_q protein. Spinal intrathecal administration of PGF_2α to mouse induces touch-evoked pain (mechanical allodynia), in which capsaicin-insensitive primary afferent Aβ-fibres and N-methyl-D-aspartate receptor ε4 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_2α-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_2αinduced mechanical allodynia and decrease of FP mRNA. With saline-administered mice, PGF_2α 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_2α-responsive cells in the slices reduced, and PGF_2α-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_2α-induced mechanical allodynia.