Emmers R
Exp Neurol. 1985 May;88(2):405-17. doi: 10.1016/0014-4886(85)90202-x.
Because increased tolerance of narcotics is marked by progressive deactivation of the descending antinociceptive system, a question was raised whether stimulation of the periaqueductal gray matter (PAG) would have any electroanalgetic effect in animals adapted to increasing doses of narcotics. The daily dose of morphine (10 mg/kg) administered to rats was increased on alternate days by 10 mg/kg to 100 mg/kg/day. To another group, the daily dose of meperidine was increased from 15 mg/kg by 15 mg/kg to 150 mg/kg/day. Electrophysiological experiments were conducted under chloralose and urethane anesthesia 16 h after the last injection of morphine or meperidine. Spike potentials evoked from individual neurons of the nucleus ventralis posterolateralis by single-pulse stimulation of the sciatic nerve were accumulated in poststimulus time histograms. For nociceptive neurons the histograms were characterized by a short-latency activity peak and at least two late (270 and 420 ms) peaks. For non-nociceptive neurons the histograms had no late activity peaks. In control rats, stimulation of the PAG (400 ms at 70/s) prior to each sciatic nerve pulse reorganized the late activity peaks of the nociceptive neurons: a single late peak occurred during the 280 to 400 ms poststimulus interval, indicating suppression of pain by electroanalgesia. In rats adapted to morphine or meperidine, intracarotid infusion of naloxone lowered the nociceptive threshold. Stimulation of the PAG reorganized the late peaks but only if the sciatic nerve stimulation was not increased. At the voltage used to stimulate the sciatic nerve in control animals, two separate late peaks appeared, which were subdued by PAG stimulation after intracarotid infusion of 5-hydroxytryptophan (5-HTP). These results affirmed previous findings that electroanalgesia is induced by activity in an ascending and a descending pathway, both originating from the PAG. Since the function of the descending pathway is impaired by repeated administration of narcotics, only the pathway ascending to the somesthetic thalamus can be activated to mask pain, unless 5-HTP is injected. The latter renews the functional capacity of the descending pathway and thus reinstates the full capacity of electroanalgesia.
由于对麻醉品耐受性的增加表现为下行抗伤害感受系统的逐渐失活，因此有人提出，对于适应逐渐增加剂量麻醉品的动物，刺激导水管周围灰质（PAG）是否会产生任何电镇痛作用。给大鼠注射的吗啡每日剂量（10毫克/千克）每隔一天增加10毫克/千克，直至100毫克/千克/天。给另一组大鼠注射的哌替啶每日剂量从15毫克/千克开始，每次增加15毫克/千克，直至150毫克/千克/天。在最后一次注射吗啡或哌替啶16小时后，在氯醛糖和乌拉坦麻醉下进行电生理实验。通过对坐骨神经进行单脉冲刺激，从腹后外侧核的单个神经元诱发的锋电位被累积到刺激后时间直方图中。对于伤害感受神经元，直方图的特征是有一个短潜伏期活动峰和至少两个晚期（270和420毫秒）峰。对于非伤害感受神经元，直方图没有晚期活动峰。在对照大鼠中，在每次坐骨神经脉冲之前刺激PAG（70次/秒，持续400毫秒）可重新组织伤害感受神经元的晚期活动峰：在刺激后280至400毫秒的间隔内出现单个晚期峰，表明电镇痛抑制了疼痛。在适应吗啡或哌替啶的大鼠中，颈内注射纳洛酮会降低伤害感受阈值。刺激PAG可重新组织晚期峰，但前提是坐骨神经刺激没有增强。在用于刺激对照动物坐骨神经的电压下，出现了两个分开的晚期峰，在颈内注射5-羟色氨酸（5-HTP）后，PAG刺激可减弱这些峰。这些结果证实了先前的发现，即电镇痛是由起源于PAG的一条上行和一条下行通路的活动诱导的。由于重复给予麻醉品会损害下行通路的功能，因此只有上行至躯体感觉丘脑的通路可以被激活以掩盖疼痛，除非注射5-HTP。后者可恢复下行通路的功能能力，从而恢复电镇痛的全部能力。
