The plasticity of descending controls in pain: translational probing
The plasticity of descending controls in pain: translational probing
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DOI：
10.1113/jp274165
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发表时间：
2017-07-01
影响因子：
5.5
通讯作者：
Dickenson, A. H.
中科院分区：
文献类型：
--
作者：
Bannister, Kirsty;Dickenson, A. H.
下行控制，包括起源于中脑和脑干区域并投射到脊髓的通路，长期以来一直被认为是相互作用产生整体疼痛体验的多个神经网络中的关键环节。临床前和临床研究有明确的证据表明，外周和中枢敏化在确定疼痛感知水平方面发挥着重要作用。人们非常重视中枢兴奋性的脊髓机制，但现在越来越清楚的是，脊髓过度兴奋性可以通过主要源自去甲肾上腺素能和血清素能系统的大脑下行通路来调节。一种痛苦可以抑制另一种痛苦。在这方面，弥漫性有害抑制控制（DNIC）是内源性下行抑制途径的一种独特形式，因为它们可以在动物和人类中轻松诱发和量化。促进 DNIC 的脊髓药理学途径很复杂；在正常情况下，这些下行控制通过去甲肾上腺素对脊髓 (2)-肾上腺素受体的作用产生最终的抑制作用，尽管作用于易化脊髓 5-HT3 受体的血清素也影响 DNIC 的最终表达。这些下行通路在神经病变中发生改变，过量血清素的作用现在可能通过激活脊髓 5-HT7 受体而变得具有抑制性。条件性疼痛调节 (CPM) 是 DNIC 的人类对应物，也需要降序控制。 DNIC 和 CPM 之间的前后转化研究（在实验室和床边进行评估）是开发利用去甲肾上腺素能和血清素能下降控制途径的镇痛疗法的关键。
Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognised as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems. One pain can inhibit another. In this respect diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous descending inhibitory pathway since they can be easily evoked and quantified in animals and man. The spinal pharmacology of pathways that subserve DNIC are complicated; in the normal situation these descending controls produce a final inhibitory effect through the actions of noradrenaline at spinal (2)-adrenoceptors, although serotonin, acting on facilitatory spinal 5-HT3 receptors, influences the final expression of DNIC also. These descending pathways are altered in neuropathy and the effects of excess serotonin may now become inhibitory through activation of spinal 5-HT7 receptors. Conditioned pain modulation (CPM) is the human counterpart of DNIC and requires a descending control also. Back and forward translational studies between DNIC and CPM, gauged between bench and bedside, are key for the development of analgesic therapies that exploit descending noradrenergic and serotonergic control pathways.