Functional characterization of prostaglandin F2alpha receptor in the spinal cord for tactile pain (allodynia).
Prostaglandin F2alpha (PGF2alpha) 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 PGF2alpha to mouse induces touch-evoked pain (mechanical allodynia), in which capsaicin-insensitive primary afferent Abeta-fibres and N-methyl-d-aspartate receptor epsilon 4 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 PGF2alpha-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 PGF2alpha-induced mechanical allodynia and decrease of FP mRNA. With saline-administered mice, PGF2alpha 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 PGF2alpha-responsive cells in the slices reduced, and PGF2alpha-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 PGF2alpha-induced mechanical allodynia.
Muratani
Tadatoshi
T
Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
Nishizawa
Mikio
M
Matsumura
Shinji
S
Mabuchi
Tamaki
T
Abe
Kohji
K
Shimamoto
Keiko
K
Minami
Toshiaki
T
Ito
Seiji
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost / Q000008:administration & dosage; D006930:Hyperalgesia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D007278:Injections, Spinal; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D014110:Touch
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D002118:Calcium