Emmers R
Exp Neurol. 1984 May;84(2):450-62. doi: 10.1016/0014-4886(84)90241-3.
Functional changes of the descending antinociceptive system were studied in morphine-dependent rats by two types of experiments: (a) by recording the effects produced on nociceptive responses of the somesthetic thalamus by stimulation of the nucleus raphe magnus (NRM), and (b) by analyzing changes in the tonic activity of neurons in the periaqueductal gray matter (PAG). Poststimulus time histograms indicated that the input of A-alpha, A-delta, and C fibers into the spinal cord was conveyed via the spinothalamic tract (STT) to particular neurons of the nucleus ventralis posterolateralis (nVPL). Spikes of their responses were grouped in a short-latency burst followed by late spikes that occurred at the appropriate intervals for the arrival of the excitations originally initiated in the A-delta and C fibers. Only the histograms with late peaks were evaluated for the influence of the antinociceptive system. Stimulation of the NRM prior to stimulation of the sciatic nerve promptly suppressed the late A-delta and C-fiber) peaks in morphine-naive animals. In morphine-dependent rats, NRM stimulation had little or no effect on the histograms. 5-Hydroxytryptophan (5-HTP) had no effect on the nVPL neurons in morphine-naive rats, but in the morphine-dependent rats it renewed the ability of NRM stimulation to suppress the late activity. The tonic activity of the PAG neurons was significantly higher in morphine-dependent compared with that of the morphine-naive animals. Naloxone had a differential effect on the activity of the PAG neurons with regard to the two types of animals: it decreased the PAG activity drastically in the morphine-dependent rats. Apparently, the high tonic activity induced in the PAG by repeated administration of morphine acts on the descending antinociceptive fibers of the NRM and exhausts the synaptic transmitter substance, serotonin, in the NRM terminals, thus decreasing the ability of these terminals to block A-delta and C-fiber excitation of the STT. By assisting the synthesis of serotonin, 5-HTP renews the capacity of the NRM fibers to counteract STT excitation, and thus reinstates the normal function of the antinociceptive system.
（a）记录刺激中缝大核（NRM）对躯体感觉丘脑伤害性反应产生的影响，以及（b）分析中脑导水管周围灰质（PAG）神经元紧张性活动的变化。刺激后时间直方图表明，A-α、A-δ和C纤维传入脊髓后通过脊髓丘脑束（STT）传导至腹后外侧核（nVPL）的特定神经元。它们反应的锋电位聚集成一个短潜伏期爆发，随后是晚期锋电位，这些晚期锋电位以适当的间隔出现，与最初由A-δ和C纤维引发的兴奋到达时间一致。仅评估具有晚期峰值的直方图以研究抗伤害感受系统的影响。在未用吗啡的动物中，在刺激坐骨神经之前刺激NRM可迅速抑制晚期A-δ和C纤维峰值。在吗啡依赖大鼠中，刺激NRM对直方图几乎没有影响。5-羟色氨酸（5-HTP）对未用吗啡的大鼠的nVPL神经元没有影响，但在吗啡依赖大鼠中，它恢复了NRM刺激抑制晚期活动的能力。与未用吗啡的动物相比，吗啡依赖大鼠中PAG神经元的紧张性活动明显更高。纳洛酮对两种动物的PAG神经元活动有不同影响：它使吗啡依赖大鼠的PAG活动急剧下降。显然，反复给予吗啡在PAG中诱导的高紧张性活动作用于NRM的下行抗伤害感受纤维，并耗尽NRM终末中的突触传递物质5-羟色胺，从而降低这些终末阻断STT的A-δ和C纤维兴奋的能力。通过协助5-羟色胺的合成，5-HTP恢复了NRM纤维对抗STT兴奋的能力，从而恢复了抗伤害感受系统的正常功能。
