Bouhassira D, Villanueva L, Le Bars D
Unité de Recherches de Neurophysiologie Pharmacologique, Institut National de la Santé et de la Recherche Médicale (U161), Paris, France.
J Pharmacol Exp Ther. 1988 Oct;247(1):332-42.
Recordings were made from convergent neurons in the lumbar dorsal horn of the rat. These neurons were activated by both innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hindpaw. Transcutaneous application of suprathreshold 2-msec square-wave pulses to the center of the receptive field resulted in responses to A- and C-fiber activation being observed: 27.2 +/- 2.2 (mean +/- S.E.M.) C-fiber latency spikes were evoked per stimulus. This type of response was inhibited by applying noxious conditioning stimuli to heterotopic areas of the body; in particular, immersing the tail in a 52 degrees C waterbath caused a 74.2 +/- 2.0% inhibition of the C-fiber evoked responses; such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC). The effects of microinjections of morphine (0.6-40 micrograms; 2 microliter) within the 3rd ventricle on both the unconditioned C-fiber-evoked responses and the inhibitory processes triggered from the tail were investigated in an attempt to answer two questions: 1) does i.c.v. morphine increase tonic descending inhibitory processes? and 2) what are the effects of i.c.v. morphine on descending inhibitory processes triggered phasically by noxious stimuli? The predominant effect of i.c.v. morphine on the C-fiber-evoked responses was a facilitation (17 of 26 cases). Such a facilitation was dose-related in the 0.6 to 40 microgram range and naloxone reversible; it plateaued from 20 min after the microinjection. No clear relationship was found between the number of C-fiber evoked responses in the control sequences and the subsequent effect of i.c.v. morphine. Intracerebroventricular morphine clearly reduced DNIC in the majority of cases (21 of 26). Such a reduction was dose-related in the 0.6 to 2.5 microgram range and naloxone reversible; it plateaued within 90 min of microinjection. No clear relationship was found between the changes in DNIC and either the number of C-fiber-evoked spikes in the control sequences or the changes in the C-fiber responses induced by i.c.v. morphine. Autoradiographic controls using [3H]morphine showed a labeling along the ventricle wall including the hypothalamus, the periaqueductal gray matter and the floor of the 4th ventricle, three regions which have been implicated in the control of nociceptive transmission at the spinal level. Diffusion from the ventricle wall was over a distance of 0.5 mm and was identical whether observed 20 or 95 min after the microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)
对大鼠腰段背角的汇聚神经元进行了记录。这些神经元可被施加于其位于同侧后爪末端的兴奋性感受野的无害和有害刺激所激活。经皮向感受野中心施加阈上2毫秒方波脉冲,可观察到对A纤维和C纤维激活的反应:每次刺激诱发27.2±2.2(平均值±标准误)个C纤维潜伏期尖峰。这种反应类型可通过对身体异位区域施加有害条件刺激而受到抑制;特别是,将尾巴浸入52℃水浴中可使C纤维诱发反应受到74.2±2.0%的抑制;这种抑制过程被称为弥漫性有害抑制控制(DNIC)。研究了在第三脑室内微量注射吗啡(0.6 - 40微克;2微升)对未条件化的C纤维诱发反应以及由尾巴触发的抑制过程的影响,试图回答两个问题:1)脑室内注射吗啡是否会增强紧张性下行抑制过程?2)脑室内注射吗啡对由有害刺激相位性触发的下行抑制过程有何影响?脑室内注射吗啡对C纤维诱发反应的主要作用是易化(26例中有17例)。这种易化在0.6至40微克范围内与剂量相关且可被纳洛酮逆转;在微量注射后20分钟达到平台期。在对照序列中C纤维诱发反应的数量与随后脑室内注射吗啡的效果之间未发现明确关系。在大多数情况下(26例中有21例),脑室内注射吗啡明显降低了DNIC。这种降低在0.6至2.5微克范围内与剂量相关且可被纳洛酮逆转;在微量注射后90分钟内达到平台期。在DNIC的变化与对照序列中C纤维诱发尖峰的数量或脑室内注射吗啡引起的C纤维反应变化之间未发现明确关系。使用[3H]吗啡的放射自显影对照显示沿着脑室壁有标记,包括下丘脑、导水管周围灰质和第四脑室底部,这三个区域与脊髓水平的伤害性传递控制有关。从脑室壁扩散的距离为0.5毫米,在微量注射后20分钟或95分钟观察时是相同的。(摘要截短至400字)