Characterization of N-methyl-D-aspartate receptor subunits responsible for postoperative pain.
N-methyl-D-aspartate (NMDA) receptors have been suggested to be critical for the development of central sensitization, which may amplify postoperative pain. NMDA receptors are formed by GluRzeta (NR1) with any one of four GluRvarepsilon1-4 (NR2A-D) subunits. To clarify the involvement of NMDA receptors in postoperative pain, we examined the effect of the GluRepsilon2-selective antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenyl piperidino)-1-propanol (CP-101,606) on postoperative pain caused by plantar incision. We also applied the postoperative pain model to GluRepsilon1 and GluRepsilon4 knockout mice. CP-101,606 administered intrathecally 30 min prior to incision significantly increased mechanical withdrawal thresholds 2 h and 1-3 days after surgery and reduced postoperative pain dose-dependently. Neither GluRvarepsilon1 nor GluRepsilon4 knockout mice showed a difference in withdrawal thresholds as compared with wild-type mice. Pretreatment with CP-101,606 did not produce an additive analgesic effect in the mice. These results demonstrate that GluRepsilon2-containing NMDA receptors are involved in postoperative pain and that CP-101,606 may be effective in reducing it.
Nishimura
Wataru
W
Department of Anesthesiology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan.
Muratani
Tadatoshi
T
Tatsumi
Shinichi
S
Sakimura
Kenji
K
Mishina
Masayoshi
M
Minami
Toshiaki
T
Ito
Seiji
S
D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000503:physiopathology / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000503:physiopathology* / Q000523:psychology; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D018091:Receptors, AMPA / Q000187:drug effects / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics
C120997:NR2A NMDA receptor; D010880:Piperidines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104724:glutamate receptor ionotropic, AMPA 4; C095106:traxoprodil mesylate