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鞘内注射NMDA和AMPA受体激动剂或拮抗剂对异丙酚抗伤害作用的影响
AIM: To study the effects of intrathecal (it) agonists and antagonists of N-methyl-D-aspartate (NMDA) and alphaamino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors and NMDAR1 antisenseoligodeoxynucleotides (AS ODN) on the antinociception of propofol. METHODS: Hot-plate test (HPPT) and acetic acid-induced writhing test were used to measure the nociceptive thresholds in mice. The effects of intrathecal NMDA, AMPA, MK-801, NBQX, or NMDAR1 AS ODN on the antinociception of propofol were observed.RESULTS: Propofol (25, 50 mg/kg, ip) displayed an appreciable antinociceptive effect in hot-plate test and acetic acid-induced writhing test. NMDA (12.5, 25 ng, it) or AMPA (1.25, 2.5 ng, it) exhibited no effects on the behavior but decreased HPPT significantly compared with basal HPPT and aCSF group (P＜0.05, P＜0.01). No effects on behavior and HPPT were obtained in NMDA (6.25 ng, it) or AMPA (0.625 ng, it) groups. NMDA (6.25, 12.5, and 25 ng, it) dose-dependently decreased the HPPT in propofol-treated group. AMPA (1.25, 2.5 ng, it) also decreased HPPT significantly. MK-801 (0.25, 0.5 μg, it) or NBQX (0.25, 0.5 μg, it) groups had no behavioral changes, two antagonists 0.5 μg but not 0.25 μg increased HPPT in conscious or propofol-treated mice. AS ODN (5, 10, and 20 μg, it) groups exhibited dose-dependent increased in HPPT in propofol-treated groups compared with aCSF group (P＜0.05, P＜0.01). CONCLUSION: Both agonists NMDA and AMPA reversed the antinociception of propofol.MK-801, NBQX, and NMDAR1 AS ODN potentiated the antinociceptive effects of propofol. Propofol produced antinociception through an interaction with spinal NMDA and AMPA receptors in mice.
