Department of Neuroscience, Physiology and Pharmacology, University College London, United Kingdom.
Pain. 2013 Aug;154(8):1263-73. doi: 10.1016/j.pain.2013.03.041. Epub 2013 Apr 6.
Translational studies are key to furthering our understanding of nociceptive signalling and bridging the gaps between molecules and pathways to the patients. This requires use of appropriate preclinical models that accurately depict outcome measures used in humans. Whereas behavioural animal studies classically involve reports related to nociceptive thresholds of, for example, withdrawal, electrophysiological recordings of spinal neurones that receive convergent input from primary afferents permits investigation of suprathreshold events and exploration of the full-range coding of different stimuli. We explored the central processing of nociceptive inputs in a novel parallel investigation between rats and humans. Using radiant laser pulses, we first compared the electrophysiological responses of deep wide dynamic range and superficial nociceptive-specific neurones in the rat dorsal horn with human psychophysics and cortical responses. Secondly, we explored the effects of spatial summation using laser pulses of identical energy and different size. We observed 3 main findings. Firstly, both rodent and human data confirmed that neodymium-yttrium aluminium perovskite laser stimulation is a nociceptive-selective stimulus that never activates Aβ afferents. Secondly, graded laser stimulation elicited similarly graded electrophysiological and behavioural responses in both species. Thirdly, there was a significant degree of spatial summation of laser nociceptive input. The remarkable similarity in rodent and human coding indicates that responses of rat dorsal horn neurones can translate to human nociceptive processing. These findings suggest that recordings of spinal neuronal activity elicited by laser stimuli could be a valuable predictive measure of human pain perception.
转化研究对于进一步了解伤害性信号以及弥合分子和途径与患者之间的差距至关重要。这需要使用适当的临床前模型，这些模型准确地描述了人类中使用的结果测量。虽然经典的行为动物研究涉及与例如撤退相关的伤害性阈值的报告，但接收来自初级传入纤维的会聚输入的脊髓神经元的电生理记录允许研究超阈值事件并探索不同刺激的全范围编码。我们在大鼠和人类之间进行了一项新的平行研究，探索了伤害性输入的中枢处理。使用辐射激光脉冲，我们首先比较了大鼠背角深部宽动态范围和浅层伤害性特异性神经元的电生理反应与人类心理物理学和皮质反应。其次，我们探索了使用相同能量和不同大小的激光脉冲进行空间总和的效果。我们观察到 3 个主要发现。首先，啮齿动物和人类数据都证实钕 - 钇 - 铝石榴石激光刺激是一种伤害性选择性刺激，永远不会激活 Aβ传入纤维。其次，分级激光刺激在两种物种中均引起类似分级的电生理和行为反应。第三，激光伤害性输入存在显著的空间总和。激光伤害性输入编码的惊人相似性表明，大鼠背角神经元的反应可以转化为人类伤害性处理。这些发现表明，激光刺激引起的脊髓神经元活动的记录可能是人类疼痛感知的有价值的预测指标。
