Kucharczyk Mateusz Wojciech, Valiente Diego, Bannister Kirsty
Central Modulation of Pain Group, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE1 1UL., UK.
J Pain Res. 2021 Apr 20;14:1083-1095. doi: 10.2147/JPR.S258602. eCollection 2021.
Bulbospinal pathways regulate nociceptive processing, and inhibitory modulation of nociception can be achieved via the activity of diffuse noxious inhibitory controls (DNIC), a unique descending pathway activated upon application of a conditioning stimulus (CS). Numerous studies have investigated the effects of varied pharmacological systems on the expression status of a) DNIC (as measured in anaesthetised animals) and b) the descending control of nociception (DCN), a surrogate measure of DNIC-like effects in conscious animals. However, the complexity of the underlying circuitry that governs initiation of a top-down inhibitory response in reaction to a CS, coupled with the methodological limitations associated with using pharmacological tools for its study, has often obscured the exact role(s) of a given drug. In this literature review, we discuss the pharmacological manipulation interrogation strategies that have hitherto been used to examine the functionality of DNIC and DCN. Discreet administration of a substance in the spinal cord or brain is considered in the context of action on one of four hypothetical systems that underlie the functionality of DNIC/DCN, where interpreting the outcome is often complicated by overlapping qualities. Systemic pharmacological modulation of DNIC/DCN is also discussed despite the fact that the precise location of drug action(s) cannot be pinpointed. Chiefly, modulation of the noradrenergic, serotonergic and opioidergic transmission systems impacts DNIC/DCN in a manner that relates to drug class, route of administration and health/disease state implicated. The advent of increasingly sophisticated interrogation tools will expedite our full understanding of the circuitries that modulate naturally occurring pain-inhibiting pathways.
延髓脊髓通路调节伤害性信息处理，通过弥漫性伤害性抑制控制（DNIC）的活动可实现对伤害感受的抑制性调节，DNIC是一种独特的下行通路，在施加条件刺激（CS）时被激活。众多研究调查了各种药理学系统对以下两方面表达状态的影响：a）DNIC（在麻醉动物中测量）；b）伤害性感受的下行控制（DCN），这是清醒动物中DNIC样效应的替代指标。然而，控制对CS产生自上而下抑制反应启动的潜在神经回路的复杂性，加上使用药理学工具进行研究时的方法学局限性，常常掩盖了特定药物的确切作用。在这篇文献综述中，我们讨论了迄今为止用于研究DNIC和DCN功能的药理学操纵询问策略。在作用于构成DNIC/DCN功能基础的四个假设系统之一的背景下，考虑在脊髓或大脑中谨慎给药一种物质，而解释结果时往往因重叠的特性而变得复杂。尽管无法精确确定药物作用的具体位置，但也讨论了对DNIC/DCN的全身药理学调节。主要地，去甲肾上腺素能、5-羟色胺能和阿片样物质传递系统的调节以与药物类别、给药途径以及所涉及的健康/疾病状态相关的方式影响DNIC/DCN。越来越复杂的询问工具的出现将加快我们对调节自然发生的疼痛抑制通路的神经回路的全面理解。
