Fields H L, Heinricher M M
Philos Trans R Soc Lond B Biol Sci. 1985 Feb 19;308(1136):361-74. doi: 10.1098/rstb.1985.0037.
Although efferent control of sensory transmission is a well-established concept, a specific network for nociceptive modulation has only recently been discovered. This network includes interconnected components at midbrain, medullary and spinal levels. At the midbrain level, electrical stimulation of the periaqueductal grey (p.a.g.) inhibits spinal neurons that respond to noxious stimuli as well as nociceptor-induced reflexes and escape behaviour in a variety of species. Midbrain stimulation also produces analgesia in patients with clinically significant pain. The rostral ventral medulla (r.v.m.) has similar behavioural and physiological effects and mediates midbrain antinociceptive actions at the level of the spinal cord. Endorphins are present at all levels of this nociceptive modulating network. Opiate microinjections at p.a.g., r.v.m. or spinal levels produce analgesia, presumably by mimicking the actions of the endorphins. The nociceptive modulatory system is diffusely organized, highly interconnected and appears to act as a unit whether activated by opiates or electrical stimulation. There are two classes of r.v.m. neurons the activity of which is correlated with the occurrence of reflexes induced by noxious stimulation. One class (the on-cell) accelerates, the other class (the off-cell) pauses just before tail flick. Both classes project to the spinal cord and are excited by electrical stimulation of the midbrain. However, when morphine is injected either systemically or into the p.a.g., the off-cell is excited and the on-cell stops firing. The off-cell is probably the r.v.m. output cell that inhibits nociceptive transmission at the level of the spinal cord. The function of the on-cell is not clear. The nociceptive modulatory system can be activated by a variety of stressful environmental factors, which are often, but not necessarily, noxious. The idea that the system acts as a simple negative feedback circuit is not consistent with its known properties.
尽管传出神经对感觉传递的控制是一个已被充分证实的概念，但伤害性调制的特定网络直到最近才被发现。该网络包括中脑、延髓和脊髓水平的相互连接的组件。在中脑水平，对导水管周围灰质（PAG）进行电刺激会抑制对有害刺激有反应的脊髓神经元，以及伤害感受器诱发的反射和多种物种的逃避行为。中脑刺激还能使有临床显著疼痛的患者产生镇痛作用。延髓头端腹内侧部（RVM）具有类似的行为和生理效应，并在脊髓水平介导中脑的抗伤害感受作用。内啡肽存在于这个伤害性调制网络的所有水平。在PAG、RVM或脊髓水平微量注射阿片类药物会产生镇痛作用，推测是通过模拟内啡肽的作用。伤害性调制系统分布广泛、高度相互连接，并且无论是由阿片类药物还是电刺激激活，似乎都作为一个整体起作用。有两类RVM神经元，其活动与有害刺激诱发的反射的发生相关。一类（开启细胞）会加速，另一类（关闭细胞）在甩尾前会暂停。这两类神经元都投射到脊髓，并受到中脑电刺激的兴奋。然而，当全身注射吗啡或向PAG注射吗啡时，关闭细胞会被兴奋，开启细胞则停止放电。关闭细胞可能是在脊髓水平抑制伤害性传递的RVM输出细胞。开启细胞的功能尚不清楚。伤害性调制系统可被多种应激性环境因素激活，这些因素通常但不一定是有害的。认为该系统作为一个简单的负反馈回路起作用的观点与其已知特性不符。
