Activation of medullary dorsal horn γ isoform of protein kinase C interneurons is essential to the development of both static and dynamic facial mechanical allodynia
Activation of medullary dorsal horn γ isoform of protein kinase C interneurons is essential to the development of both static and dynamic facial mechanical allodynia
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DOI：
10.1111/ejn.13165
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发表时间：
2016-03-01
影响因子：
3.4
通讯作者：
Artola, Alain
中科院分区：
文献类型：
--
作者：
Pham-Dang, Nathalie;Descheemaeker, Amelie;Artola, Alain
蛋白激酶C（PKC）的亚型集中在脊髓背角和延髓背角（MDH）的内层II（IIi）内的特定类别的中间神经元中，已知其参与机械性异常性疼痛的发展，机械性异常性疼痛是炎性或神经性疼痛的广泛且顽固的症状。然而，尽管在疼痛的动物模型中，在神经损伤或抑制减少后，PKC的遗传和药理学损伤被证明可以防止机械异常性疼痛，但单独PKC激活对机械敏感性的功能后果仍然未知。在大鼠MDH中使用行为和解剖学方法，我们测试了幼稚动物中PKC激活是否足以建立机械性异常性疼痛。脑池内注射佛波醇酯，12，13-二丁酸酯伴随诱导静态以及动态面部机械异常性疼痛。磷酸化细胞外信号调节激酶1和2的免疫反应性监测内的MDH的神经元活动显示，激活的第一层外板II和III层外板III神经元，包括板IIIPKC表达的中间神经元，与机械异常性疼痛的表现。佛波酯、12，13-二丁酸酯诱导的机械性异常性疼痛和相关的神经元激活均通过用KIG 31 -1选择性抑制节段性PKC来预防。我们的研究结果表明，PKC激活，没有任何其他实验操作，是足够的静态和动态机械异常性疼痛的发展。板层III-PKC中间神经元已被证明是直接激活的低阈值机械输入进行有髓鞘传入。因此，PKC中间神经元内的PKC激活水平可能控制无害的机械输入到I层（伤害性输出神经元）的传递，从而将触摸转变为疼痛。
The isoform of protein kinase C (PKC), which is concentrated in a specific class of interneurons within inner lamina II (IIi) of the spinal dorsal horn and medullary dorsal horn (MDH), is known to be involved in the development of mechanical allodynia, a widespread and intractable symptom of inflammatory or neuropathic pain. However, although genetic and pharmacological impairment of PKC were shown to prevent mechanical allodynia in animal models of pain, after nerve injury or reduced inhibition, the functional consequences of PKC activation alone on mechanical sensitivity are still unknown. Using behavioural and anatomical approaches in the rat MDH, we tested whether PKC activation in naive animals is sufficient for the establishment of mechanical allodynia. Intracisternal injection of the phorbol ester, 12,13-dibutyrate concomitantly induced static as well as dynamic facial mechanical allodynia. Monitoring neuronal activity within the MDH with phospho-extracellular signal-regulated kinases 1 and 2 immunoreactivity revealed that activation of both lamina I-outer lamina II and IIi-outer lamina III neurons, including lamina IIi PKC-expressing interneurons, was associated with the manifestation of mechanical allodynia. Phorbol ester, 12,13-dibutyrate-induced mechanical allodynia and associated neuronal activations were all prevented by inhibiting selectively segmental PKC with KIG31-1. Our findings suggest that PKC activation, without any other experimental manipulation, is sufficient for the development of static and dynamic mechanical allodynia. Lamina IIi PKC interneurons have been shown to be directly activated by low-threshold mechanical inputs carried by myelinated afferents. Thus, the level of PKC activation within PKC interneurons might gate the transmission of innocuous mechanical inputs to lamina I, nociceptive output neurons, thus turning touch into pain.