2003 Fiscal Year Final Research Report Summary
Studies on pain measurements by the confocal laser scanning microscopy
| Project/Area Number |
13671620
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Osaka Medical College |
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Principal Investigator |
KUROSAKI Akiko Osaka Medical College, Faculty of Medicine, Assistant, 医学部, 助手 (20351413)
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| Co-Investigator(Kenkyū-buntansha) |
MINAMI Toshiaki Osaka Medical College, Faculty of Medicine, Professor, 医学部, 教授 (00257841)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Allodynia / Knockout mice / Prostaglandin / Nitric oxide / Nociceptin / orphanin FQ |
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| Research Abstract |
Functional evidence for interaction between prostaglandin EP3 and κ-opioid pathways in tactile pain induced by human immunodeficiency virus type-1 (HIV-1) glycoprotein gp120
HIV-1 glycoprotein gp120 administrated intrathecally induces tactile pain (allodynia) in animals. In the present study, we investigated the mechanism of gp120-induced allodynia. Gp120 evoked allodynia in a dose-dependent manner with the maximum effect at 1 pg/mouse. Gp120 stimulated a rapid increase in intracellular free Ca^<2+> concentration ([Ca^<2+>]i) in the dorsal horn cells of the spinal cord. The gp120-induced allodynia was attenuated by indomethacin that inhibits prostaglandin synthesis, and did not develop in mice lacking PGE receptor EP3 subtype (EP3^<-/->). Pretreatment of spinal slices with indomethacin dose-dependently decreased the percentage of the cells which increased [Ca^<2+>]i in response to gp120, and the decrease was reversed by addition of the selective EP3 agonist. The κ-opioid agonist U-50,48
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8 significantly enhanced the gp120-stimulated increase in [Ca^<2+>]i in spinal slices prepared from EP3^<-/-> mice and simultaneous addition of U-50,488 with gp120 reproduced the gp120-induced allodynia in EP3^<-/-> mice. These results suggest that gp120 induces allodynia by increasing [Ca^<2+>]i followed by activation of EP3 and κ-opioid receptors in the spinal cord.
Functional characterization of prostaglandin F_2α receptor in the spinal cord for tactile pain (allodynia)
PGF_2α binds to its receptor (FP) to increase [Ca^<2+>]i by coupling of FP with G_qprotein. Spinal intrathecal administration of PGF_2α to mouse induces allodynia. 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 allodynia. We identified an antisense oligodeoxyribonucleotide targeting FP mRNA, causing both disappearance of PGF_2α-induced allodynia and decrease of FP mRNA. With saline-administered mice, PGF_2α rapidly increased [Ca^<2+>]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 [Ca^<2+>]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 allodynia. Less
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