Minami T, Matsumura S, Okuda-Ashitaka E, Shimamoto K, Sakimura K, Mishina M, Mori H, Ito S
Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686, Japan.
Brain Res. 2001 Mar 23;895(1-2):178-85. doi: 10.1016/s0006-8993(01)02069-8.
Glutamate is the main excitatory neurotransmitter in the central nervous system and has been shown to be involved in spinal nociceptive processing. We previously demonstrated that intrathecal (i.t.) administration of prostaglandin (PG) E(2) and PGF(2 alpha) induced touch-evoked pain (allodynia) through the glutamatergic system by different mechanisms. In the present study, we characterized glutamate receptor subtypes and glutamate transporters involved in induction and maintenance of PGE(2)- and PGF(2 alpha)-evoked allodynia. In addition to PGE(2) and PGF(2 alpha), N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not kainate, induced allodynia. PGE(2)- and NMDA-induced allodynia were observed in NMDA receptor epsilon 4 (NR2D) subunit knockout (GluR epsilon 4(-/-)) mice, but not in epsilon 1 (NR2A) subunit knockout (GluR epsilon 1(-/-)) mice. Conversely, PGF(2 alpha)- and AMPA-induced allodynia were observed in GluR epsilon 1(-/-) mice, but not in GluR epsilon 4(-/-) mice. The induction of allodynia by PGE(2) and NMDA was abolished by the NMDA receptor epsilon 2 (NR2B) antagonist CP-101,606 and neonatal capsaicin treatment. PGF(2 alpha)- and AMPA-induced allodynia were not affected by CP-101,606 and by neonatal capsaicin treatment. On the other hand, the glutamate transporter blocker DL-threo-beta-benzyloxyaspartate (DL-TBOA) blocked all the allodynia induced by PGE(2), PGF(2 alpha), NMDA, and AMPA. These results demonstrate that there are two pathways for induction of allodynia mediated by the glutamatergic system and suggest that the glutamate transporter is essential for the induction and maintenance of allodynia.
谷氨酸是中枢神经系统中主要的兴奋性神经递质，已被证明参与脊髓伤害性感受处理。我们之前证明，鞘内注射前列腺素（PG）E2和PGF2α通过谷氨酸能系统，通过不同机制诱发触觉诱发疼痛（异常性疼痛）。在本研究中，我们对参与PGE2和PGF2α诱发异常性疼痛的诱导和维持的谷氨酸受体亚型和谷氨酸转运体进行了表征。除了PGE2和PGF2α，N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA），但不是海人藻酸，可诱发异常性疼痛。在NMDA受体ε4（NR2D）亚基敲除（GluR ε4（-/-））小鼠中观察到PGE2和NMDA诱发的异常性疼痛，但在ε1（NR2A）亚基敲除（GluR ε1（-/-））小鼠中未观察到。相反，在GluR ε1（-/-）小鼠中观察到PGF2α和AMPA诱发的异常性疼痛，但在GluR ε4（-/-）小鼠中未观察到。PGE2和NMDA诱发的异常性疼痛可被NMDA受体ε2（NR2B）拮抗剂CP-101,606和新生期辣椒素处理消除。PGF2α和AMPA诱发的异常性疼痛不受CP-101,606和新生期辣椒素处理的影响。另一方面，谷氨酸转运体阻滞剂DL-苏式-β-苄氧基天冬氨酸（DL-TBOA）可阻断由PGE2、PGF2α、NMDA和AMPA诱发的所有异常性疼痛。这些结果表明，谷氨酸能系统介导的异常性疼痛诱导有两条途径，并表明谷氨酸转运体对异常性疼痛的诱导和维持至关重要。
