Heitler Bill
School of Psychology and Neuroscience, University of St Andrews, Fife KY16 9JP, United Kingdom.
J Undergrad Neurosci Educ. 2023 Dec 17;22(1):A58-A65. doi: 10.59390/PWFC1224. eCollection 2023 Fall.
The gate control theory of pain postulates that the sensation of pain can be reduced or blocked by closing a "gate" at the earliest synaptic level in the spinal cord, where nociceptive (pain) afferents excite the ascending interneurons that transmit the signal to the brain. Furthermore, the gate can be induced to close by stimulating touch afferents with receptive fields in the same general area as the trauma that is generating the pain (the "rub it to make it better" effect). A considerable volume of research has substantiated the theory and shown that a key mechanism mediating the gate is pre-synaptic inhibition, and that this inhibition is generated by depolarizing IPSPs in the nociceptor central terminals (primary afferent depolarization; PAD). Both pre-synaptic inhibition and depolarizing IPSPs are topics that students often regard as matters of secondary importance (if they are aware of them at all), and yet they are crucial to a matter of primary importance to us all - pain control. This report describes some simple computer simulations that illustrate pre-synaptic inhibition and explore the importance of the depolarizing aspect of the IPSPs. These concepts are then built into a model of the gate control of pain itself. Finally, the simulations show how a small change in chloride homeostasis can generate the dorsal root reflex, in which nociceptor afferents generate antidromic spikes which may increase neurogenic inflammation and actually exacerbate pain. The hope is that the simulations will increase awareness and understanding of a topic that is important in both basic neuroscience and medical neurology.
疼痛的闸门控制理论假定，在脊髓最早的突触水平关闭一个“闸门”，可以减轻或阻断疼痛感觉，在这个水平，伤害性（疼痛）传入神经会激发将信号传递至大脑的上行中间神经元。此外，通过刺激与产生疼痛的创伤处于同一大致区域的具有感受野的触觉传入神经，可促使闸门关闭（即“揉一揉就好点”的效果）。大量研究证实了该理论，并表明介导闸门的一个关键机制是突触前抑制，且这种抑制是由伤害感受器中枢终末处的去极化抑制性突触后电位（初级传入去极化；PAD）产生的。突触前抑制和去极化抑制性突触后电位都是学生们通常认为不太重要的主题（如果他们根本了解这些主题的话），然而它们对于我们所有人都至关重要的一件事——疼痛控制来说却是关键所在。本报告描述了一些简单的计算机模拟，这些模拟阐释了突触前抑制，并探讨了抑制性突触后电位去极化方面的重要性。然后将这些概念纳入疼痛本身的闸门控制模型中。最后，模拟展示了氯离子内环境稳定的微小变化如何产生背根反射，在背根反射中，伤害感受器传入神经产生逆向冲动，这可能会增加神经源性炎症并实际上加剧疼痛。希望这些模拟能够提高人们对一个在基础神经科学和医学神经学中都很重要的主题的认识和理解。
