Emmers R
Exp Neurol. 1984 Jan;83(1):118-33. doi: 10.1016/0014-4886(84)90051-7.
Rats were injected with progressively increasing doses of morphine or meperidine during a period of 3 to 40 days. From this colony of animals individual rats were used at 3- to 4-day intervals for electrophysiologic experiments to analyze the activity of nociceptive neurons in the somesthetic thalamus. After an i.p. injection of chloralose-urethane and the appropriate preparation for a stereotaxic microelectrode penetration of the thalamus, a nociceptive neuron was identified in the nucleus ventralis posterolateralis by its unique spacing of spike potentials emitted in response to pricking the foot with a pin. In addition to the short-latency response that formed a high activity peak on poststimulus time histograms, spikes following the stimulus up to 500 ms also formed activity peaks. Single-pulse stimulation of the sciatic nerve evoked the same response as pinpricks, but innocuous stimuli (pin shielded with a piece of cork) evoked a response without the late activity peaks. Only neurons that exhibited this differential response were regarded as nociceptive. Their response and spontaneous activity were accumulated separately on a digital computer. Following this, naloxone was infused i.v. and the computer accumulations were repeated. It was found that during naloxone-precipitated narcotic withdrawal, innocuous stimuli evoked responses indicative of pain; the nociceptive system was sensitized. Furthermore, a small dose or morphine or meperidine heightened the sensitization. This action of the narcotic agents was reversed by 5-hydroxytryptophan, which assisted the narcotics in suppressing pain in morphine- or meperidine-dependent rats but had no demonstrable effect in control animals. The spontaneous tonic activity of the nociceptive neurons of the somesthetic thalamus was high in rats exhibiting narcotic dependence. Naloxone decreased the count, but not to the value of the control animals. The sensitization of nociception can be explained by a decreased action of a neural pathway that descends from the periaqueductal gray matter via the nucleus raphe magnus to the spinal cord and there blocks the excitation of the spinothalamic tract cells by A-delta and C fibers. The mechanisms that increase the spontaneous activity of the thalamic nociceptive neurons remain unclear.
在3至40天的时间段内，给大鼠注射剂量逐渐增加的吗啡或哌替啶。从这群动物中，每隔3至4天挑选个体大鼠用于电生理实验，以分析躯体感觉丘脑内伤害性神经元的活动。腹腔注射水合氯醛 - 乌拉坦并进行适当准备以便立体定位微电极穿刺丘脑后，通过对大鼠足部进行针刺时所发出的独特峰电位间隔，在丘脑腹后外侧核中识别出一个伤害性神经元。除了在刺激后时间直方图上形成高活动峰值的短潜伏期反应外，刺激后长达500毫秒的峰电位也形成活动峰值。坐骨神经的单脉冲刺激诱发的反应与针刺相同，但无害刺激（用一块软木塞屏蔽的针）诱发的反应没有后期活动峰值。只有表现出这种差异反应的神经元才被视为伤害性神经元。它们的反应和自发活动分别在数字计算机上进行累加。在此之后，静脉注射纳洛酮并重复计算机累加。结果发现，在纳洛酮诱发的麻醉戒断期间，无害刺激诱发了表明疼痛的反应；伤害性系统被致敏。此外，小剂量的吗啡或哌替啶增强了这种致敏作用。麻醉剂的这种作用被5 - 羟色氨酸逆转，5 - 羟色氨酸在吗啡或哌替啶依赖的大鼠中协助麻醉剂抑制疼痛，但在对照动物中没有明显效果。在表现出麻醉依赖的大鼠中，躯体感觉丘脑伤害性神经元的自发紧张性活动很高。纳洛酮减少了计数，但未降至对照动物的值。伤害感受的致敏作用可以通过一条神经通路的作用减弱来解释，该神经通路从导水管周围灰质经中缝大核下行至脊髓，并在脊髓处阻断A - δ和C纤维对脊髓丘脑束细胞的兴奋。增加丘脑伤害性神经元自发活动的机制仍不清楚。
