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October 26, 2005
9:00:00 AM - 11:00:00 AM
Hall C4
Effects of NMDA and AMPA Receptors Agonists or Antagonists on Antinociception of Propofol
Aijun Xu, M.D., Hong Cao, M.D., Jun Li, M.D., Ph.D., Shiming Duan, B.S., Yinming Zeng, M.D.
Anesthesiology, 2nd Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China
AIM: To investigate the interaction between NMDA and AMPA receptors in the central nervous system and propofol.

METHODS: The recovery time of righting reflex(RT)was recorded; Hot-plate test 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: Compared with aCSF group, RT of 0.05μg or 0.075μg NMDA groups had no difference, however, RT of 0.1μg NMDA group was prolonged significantly; RT of 0.05μg AMPA group had no difference, RT of 0.075μg or 0.1μg AMPA groups were prolonged significantly; RT of 2μg MK-801 group had no difference, but RT of 4 or 8μg MK-801 groups were prolonged significantly, RT of 0.5,2 or 4μg NBQX groups were all prolonged significantly. Comparing with aCSF group, NMDA 0.05μg or AMPA 0.05μg decreased the pain threshold in hot-plate test (HPPT) slightly but had no difference; 2μg MK-801 or 0.5μg NBQX both increased the HPPT significantly. Propofol (25, 50 mg/kg, ip) displayed an appreciable antinociceptive effect in HPPT and the pain threshold in 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 observed 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 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) 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) exhibited dose-dependent increase in HPPT in propofol-treated groups compared with aCSF group (P<0.05, P<0.01).

CONCLUSION: NMDA or AMPA had no effects on the general anesthesia of propofol, but MK-801 and NBQX had dose-dependent synergism with propofol. Both agonists NMDA and AMPA reversed the antinociception of propofol. MK-801, NBQX and NMDAR1 AS ODN potentiated the antinociceptive effects of propofol. Propofol produces antinociception through an interaction with spinal NMDA and AMPA receptors in mice.

Key Words:N-methyl-D-aspartate, Receptors; AMPA, Receptors; antinociception; propofol

Anesthesiology 2005; 103: A1091