Spinella Marcello, Cooper Madeline L, Bodnar Richard J
Department of Psychology and Neuropsychology Doctoral Subprogram, Queens College, City University of New York, Flushing, NY 11367, USA.
Pain. 1996 Mar;64(3):545-552. doi: 10.1016/0304-3959(95)00192-1.
Supraspinal opioid analgesia is mediated in part by connections between the periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Morphine analgesia elicited from the PAG is respectively decreased by selective serotonergic and opioid receptor antagonists administered into the RVM, and increased by RVM neurotensin antagonists. Since glutamate and excitatory amino acid (EAA) receptors are also active in the RVM, the present study evaluated whether either competitive (AP7) or non-competitive (MK-801) N-methyl-D-aspartate (NMDA) antagonists or a kainate/AMPA (CNQX) antagonist microinjected into the RVM altered morphine (2.5 micrograms) analgesia elicited from the PAG as measured by the tail-flick and jump tests. Mesencephalic morphine analgesia was markedly reduced on both tests after RVM pretreatment with either AP7 (0.01-1 microgram, 0.08-7.8 nmol) or MK-801 (0.03-3 micrograms, 0.04-4.4 nmol). In contrast, small but significant reductions in mesencephalic morphine analgesia occurred on the jump test following CNQX (0.5 microgram, 2.2 nmol) in the RVM. NMDA antagonists did not markedly alter either basal nociceptive thresholds following RVM administration, or mesencephalic morphine analgesia following administration into medullary placements lateral or dorsal to the RVM. These data implicate EAA and particularly NMDA receptors in the RVM in modulating the transmission of opioid pain-inhibitory signals from the PAG.
脊髓上阿片类镇痛作用部分是由中脑导水管周围灰质（PAG）和延髓头端腹内侧区（RVM）之间的联系介导的。从PAG引发的吗啡镇痛作用分别被注入RVM的选择性5-羟色胺能和阿片受体拮抗剂降低，而被RVM神经降压素拮抗剂增强。由于谷氨酸和兴奋性氨基酸（EAA）受体在RVM中也有活性，本研究评估了注入RVM的竞争性（AP7）或非竞争性（MK-801）N-甲基-D-天冬氨酸（NMDA）拮抗剂或一种海人藻酸/α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）拮抗剂（CNQX）是否会改变通过甩尾和跳跃试验测量的从PAG引发的吗啡（2.5微克）镇痛作用。在用AP7（0.01 - 1微克，0.08 - 7.8纳摩尔）或MK-801（0.03 - 3微克，0.04 - 4.4纳摩尔）对RVM进行预处理后，两种试验中的中脑吗啡镇痛作用均显著降低。相比之下，在RVM中注入CNQX（0.5微克，2.2纳摩尔）后，跳跃试验中的中脑吗啡镇痛作用出现了小幅度但显著的降低。NMDA拮抗剂在注入RVM后并未显著改变基础伤害性感受阈值，也未改变注入RVM外侧或背侧髓质部位后的中脑吗啡镇痛作用。这些数据表明RVM中的EAA尤其是NMDA受体参与调节来自PAG的阿片类疼痛抑制信号的传递。
