Functional characterization of prostaglandin F2α receptor in the spinal cord for tactile pain (allodynia)
Functional characterization of prostaglandin F2α receptor in the spinal cord for tactile pain (allodynia)
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DOI：
10.1046/j.1471-4159.2003.01840.x
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发表时间：
2003-07-01
影响因子：
4.7
通讯作者：
Ito, S
中科院分区：
文献类型：
--
作者：
Muratani, T;Nishizawa, M;Ito, S
前列腺素 F-2α (PGF(2α) ) 与其受体 (FP) 结合，通过 FP 与 G(q) 蛋白偶联来增加细胞内游离钙浓度 ([Ca2+ ]i)。对小鼠进行脊髓鞘内注射 PGF(2α) 可诱导触摸诱发疼痛（机械性异常性疼痛），其中涉及辣椒素不敏感的初级传入 Abeta 纤维和 N-甲基-d-天冬氨酸受体 ε4 亚基。然而，脊髓中的 FP 尚未得到很好的表征。在这里，我们展示了小鼠脊髓中 FP mRNA 的组成型表达，并对参与 PGF(2α) 诱导的机械异常性疼痛的脊髓 FP 表达细胞进行了功能表征。建立了通过管道对清醒小鼠重复施用寡脱氧核糖核苷酸的方法，用于机械异常性疼痛评估。我们鉴定了一种针对 FP mRNA 的反义寡脱氧核糖核苷酸，导致 PGF(2α) 诱导的机械异常性疼痛消失和 FP mRNA 减少。对于给予盐水的小鼠，PGF(2α) 迅速增加背角深层细胞的[Ca2+]i。相反，当重复施用FP反义寡脱氧核糖核苷酸时，切片中PGF(2α)反应性细胞的数量减少，并且PGF(2α)诱导的这些细胞的[Ca2+]i增加减少。这些数据强烈表明，在脊髓的背角中，存在与PGF(2α)诱导的机械性异常性疼痛有关的表达FP的细胞。
Prostaglandin F-2alpha (PGF(2alpha) ) 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(2alpha) to mouse induces touch-evoked pain (mechanical allodynia), in which capsaicin-insensitive primary afferent Abeta-fibres and N -methyl-d-aspartate receptor epsilon4 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(2alpha) -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(2alpha) -induced mechanical allodynia and decrease of FP mRNA. With saline-administered mice, PGF(2alpha) 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(2alpha) -responsive cells in the slices reduced, and PGF(2alpha) -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(2alpha) -induced mechanical allodynia.