Prescott Steven A
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Prog Mol Biol Transl Sci. 2015;131:359-83. doi: 10.1016/bs.pmbts.2014.11.008. Epub 2015 Jan 30.
Nociceptive signals originating in the periphery must be transmitted to the brain to evoke pain. Rather than being conveyed unchanged, those signals undergo extensive processing in the spinal dorsal horn. Synaptic inhibition plays a crucial role in that processing. On the one hand, neuropathy and inflammation are associated with reduced spinal inhibition; on the other hand, the hypersensitivity associated with inflammatory and neuropathic pain can be reproduced by blocking inhibition at the spinal level. To understand the consequences of disinhibition and how to therapeutically reverse it, one must understand how synaptic inhibition normally operates. To that end, this chapter will discuss the structure and function of GABAA and glycine receptors together with the role of associated molecules involved in transmitter handling and chloride regulation. Mechanisms by which inhibition modulates cellular excitability will be described. The chapter will end with discussion of how inhibition goes awry under pathological conditions and what the implications are for the treatment of resulting pain.
源自外周的伤害性信号必须传递至大脑才能引起疼痛。这些信号并非原封不动地传导，而是在脊髓背角经历广泛的加工处理。突触抑制在这一加工过程中起着关键作用。一方面，神经病变和炎症与脊髓抑制作用减弱有关；另一方面，通过阻断脊髓水平的抑制作用，可以重现与炎性疼痛和神经性疼痛相关的超敏反应。为了理解去抑制的后果以及如何通过治疗逆转去抑制，必须了解突触抑制的正常运作方式。为此，本章将讨论GABAA和甘氨酸受体的结构与功能，以及参与递质处理和氯离子调节的相关分子的作用。将描述抑制调节细胞兴奋性的机制。本章最后将讨论在病理条件下抑制作用如何出现异常，以及这对由此产生的疼痛治疗有何意义。
