Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice

被引:200
作者
Eguchi, N
Minami, T
Shirafuji, N
Kanaoka, Y
Tanaka, T
Nagata, A
Yoshida, N
Urade, Y
Ito, S
Hayaishi, O [1 ]
机构
[1] Osaka Biosci Inst, Dept Mol Behav Biol, Osaka 5650874, Japan
[2] Univ Tokyo, Fac Med, Dept Biochem, Tokyo 1130033, Japan
[3] Kansai Med Univ, Dept Med Chem, Osaka 5708506, Japan
[4] Osaka Med Ctr Maternal & Child Hlth, Res Inst, Div Mol & Cellular Immunol, Osaka 5941101, Japan
[5] Osaka Med Coll, Dept Anesthesiol, Osaka 5698686, Japan
[6] Osaka Biosci Inst, Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Osaka 5650874, Japan
[7] Kyoto Univ, Fac Med, Dept Morphol Brain Sci, Kyoto 6068315, Japan
[8] Japan Sci & Technol Corp, Precursory Res Embryon Sci & Technol, Kyoto 6068315, Japan
关键词
gene targeting; hyperalgesia;
D O I
10.1073/pnas.96.2.726
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Prostaglandin (PG) D-2 is the most abundant prostanoid produced in the central nervous system of mammals and has been implicated in the modulation of neural functions such as sleep induction, nociception, regulation of body temperature, and odor responses. We generated gene-knockout mice for lipocalin-type PGD(2) synthase (L-PGDS) and found that the intrathecal administration of PGE(2), an endogenous pain-producing substance, failed to elicit allodynia (touch-evoked pain), which is one typical phenomenon of neuropathic pain, whereas it evoked thermal hyperalgesia, in L-PGDS-/- mice. We also found that the allodynic response induced by the gamma-aminobutyric acid (GABA)(A) receptor antagonist bicuculline was selectively abolished in the L-PGDS-/- mice, among excitatory and inhibitory agents that induced allodynia in wild-type mice. interestingly, simultaneous injection of a femtogram amount of PGD(2) with PGE(2) or bicuculline induced allodynia in L-PGDS-/- mice to the same extent as in wild-type mice. The PGE(2)- or bicuculline-evoked allodynia in wild-type and in PGD(2)-supplemented L-PGDS-/- mice was blocked by a PGD(2) receptor antagonist given in a femtogram amount. These results reveal that endogenous PGD(2) is essential for both PGE(2)- and bicuculline-induced allodynia.
引用
收藏
页码:726 / 730
页数:5
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