Touch Receptor-Derived Sensory Information Alleviates Acute Pain Signaling and Fine-Tunes Nociceptive Reflex Coordination
Touch Receptor-Derived Sensory Information Alleviates Acute Pain Signaling and Fine-Tunes Nociceptive Reflex Coordination
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DOI：
10.1016/j.neuron.2016.11.027
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发表时间：
2017-01-04
期刊：
影响因子：
16.2
通讯作者：
Lechner, Stefan G.
中科院分区：
文献类型：
--
作者：
Arcourt, Alice;Gorham, Louise;Lechner, Stefan G.
疼痛性机械刺激同时激活多种外周感觉传入亚型，包括伤害感受器和低阈值机械感受器（LTMR）。使用光遗传学方法，我们证明LTMR不仅作为触觉受体，而且在急性疼痛信号传导中发挥重要作用。我们发现，选择性激活神经肽Y受体-2-表达（Npy 2 r）的有髓A-纤维伤害感受器引起异常加剧的疼痛，这是缓解的LTMR的同时激活的频率依赖性的方式。我们进一步表明，从多个NPY 2 R阳性传入的单个动作电位的空间总和是足以触发疼痛性缩爪，但额外的同时从LTMR的感觉输入需要正常的协调执行这个反射。因此，我们的研究结果表明，组合编码的伤害和触觉感觉输入所需的正常急性机械疼痛信号。此外，我们在功能鉴定的感觉神经元亚群中精确定义的神经活动与伤害反应行为和疼痛之间建立了因果关系。
Painful mechanical stimuli activate multiple peripheral sensory afferent subtypes simultaneously, including nociceptors and low-threshold mechano-receptors (LTMRs). Using an optogenetic approach, we demonstrate that LTMRs do not solely serve as touch receptors but also play an important role in acute pain signaling. We show that selective activation of neuropeptide Y receptor-2-expressing (Npy2r) myelinated A-fiber nociceptors evokes abnormally exacerbated pain, which is alleviated by concurrent activation of LTMRs in a frequency-dependent manner. We further show that spatial summation of single action potentials from multiple NPY2R-positive afferents is sufficient to trigger nocifensive paw withdrawal, but additional simultaneous sensory input from LTMRs is required for normal well-coordinated execution of this reflex. Thus, our results show that combinatorial coding of noxious and tactile sensory input is required for normal acute mechanical pain signaling. Additionally, we established a causal link between precisely defined neural activity in functionally identified sensory neuron subpopulations and nocifensive behavior and pain.