Feng J, Kendig J J
Department of Anesthesia, Stanford University School of Medicine, CA 94305, USA.
Neurosci Lett. 1995 Apr 14;189(2):128-30. doi: 10.1016/0304-3940(95)11465-9.
In isolated neonatal rat spinal cord, naloxone administered after an opioid increases a nociceptive-related slow ventral root potential (sVRP) to levels above pre-drug controls. We studied the role of N-methyl-D-aspartate (NMDA) receptors in this phenomenon, which may be related to acute tolerance and to hyperalgesia on antagonist-precipitated withdrawal. Naloxone (200 nM) alone produced no significant effect on sVRP area, while naloxone (560 nM) increased area to 121 +/- 17.7% of control (mean +/- SD). Following 200 nM alfentanil, naloxone (200 nM) was associated with a significant rebound in sVRP area to 138 +/- 18.0% of pre-drug control. Hyperresponsiveness developed within 7 min of initial alfentanil exposure. The non-competitive NMDA antagonist MK-801 (20 nM) had no effect on sVRP area when applied alone; higher concentrations produced irreversible depression. MK-801 (20 nM) co-applied with 200 nM alfentanil blocked the rebound increase in sVRP area following naloxone 200 nM and also the increase following naloxone alone (560 nM). The results suggest that alfentanil induces a rapid NMDA receptor-dependent change in spinal cord neuronal excitability.
在新生大鼠离体脊髓中，阿片类药物作用后给予纳洛酮可使伤害性相关的慢腹根电位（sVRP）升高至高于用药前对照水平。我们研究了N-甲基-D-天冬氨酸（NMDA）受体在此现象中的作用，该现象可能与急性耐受性以及拮抗剂诱发戒断时的痛觉过敏有关。单独使用纳洛酮（200 nM）对sVRP面积无显著影响，而纳洛酮（560 nM）可使面积增加至对照值的121±17.7%（平均值±标准差）。给予200 nM阿芬太尼后，纳洛酮（200 nM）可使sVRP面积显著反弹至用药前对照值的138±18.0%。在首次接触阿芬太尼后7分钟内出现高反应性。非竞争性NMDA拮抗剂MK-801（20 nM）单独应用时对sVRP面积无影响；较高浓度会产生不可逆的抑制作用。MK-801（20 nM）与200 nM阿芬太尼共同应用可阻断200 nM纳洛酮给药后sVRP面积的反弹增加，以及单独使用纳洛酮（560 nM）后的增加。结果表明，阿芬太尼可诱导脊髓神经元兴奋性快速发生依赖于NMDA受体的变化。
