Effects of intrathecal NMDA and AMPA receptors agonists or antagonists on antinociception of propofol.
OBJECTIVE
To study the effects of intrathecal (it) agonists and antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors and NMDAR1 antisense oligodeoxynucleotides (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 microg, it) or NBQX (0.25, 0.5 microg, it) groups had no behavioral changes, two antagonists 0.5 microg but not 0.25 microg increased HPPT in conscious or propofol-treated mice. AS ODN (5, 10, and 20 microg, it) groups exhibited dose-dependent increased in HPPT in propofol-treated groups compared with aCSF group (P<0.05, P<0.01).


CONCLUSIONS
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.
Xu
Ai-Jun
AJ
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, China.
Duan
Shi-Ming
SM
Zeng
Yin-Ming
YM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000700:Analgesics; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D015742:Propofol