Chronic pain is a frequent and disabling condition that is significantly maintained by central sensitization, which results in pathological amplification of responses to noxious and innocuous stimuli. As such, mechanical allodynia, or pain in response to a tactile stimulus that does not normally provoke pain, is a cardinal feature of chronic pain. Recent evidence suggests that the dorsal horn excitatory interneurons that express the γ isoform of protein kinase C (PKCγ) play a critical role in the mechanism of mechanical allodynia during chronic pain. Here, we review this evidence as well as the main aspects of the development, anatomy, electrophysiology, inputs, outputs, and pathophysiology of dorsal horn PKCγ neurons. Primary afferent high-threshold neurons transmit the nociceptive message to the dorsal horn of the spinal cord and trigeminal system where it activates second-order nociceptive neurons relaying the information to the brain. In physiological conditions, low-threshold mechanoreceptor inputs activate inhibitory interneurons in the dorsal horn, which may control activation of second-order nociceptive neurons. During chronic pain, low-threshold mechanoreceptor inputs now activate PKCγ neurons that forward the message to second-order nociceptive neurons, turning thus tactile inputs into pain. Several mechanisms may contribute to opening this gate, including disinhibition, activation of local astrocytes, release of diffusible factors such as reactive oxygen species, and alteration of the descending serotoninergic control on PKCγ neurons through 5-HT2A serotonin receptors. Dorsal horn PKCγ neurons, therefore, appear as a relevant therapeutic target to alleviate mechanical allodynia during chronic pain.

中文翻译：

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PKCγinterneurons，通向背角病理性疼痛的门户。

慢性疼痛是一种常见的致残性疾病，可通过中枢敏化显着维持，从而导致对有害和无害刺激的反应发生病理放大。这样，机械性异常性疼痛或对通常不引起疼痛的触觉刺激的响应引起的疼痛是慢性疼痛的主要特征。最近的证据表明，表达蛋白激酶C（PKCγ）的γ亚型的背角兴奋性中间神经元在慢性疼痛期间的机械性异常性疼痛的机制中起关键作用。在这里，我们审查此证据以及背角PKCγ神经元的发育，解剖学，电生理学，输入，输出和病理生理学的主要方面。原发性高阈值神经元将伤害性信息传递到脊髓和三叉神经系统的背角，在那里它激活将信息传递到大脑的二阶伤害性神经元。在生理条件下，低阈值机械感受器输入会激活背角中的抑制性中间神经元，这可能会控制二阶伤害感受神经元的激活。现在，在慢性疼痛中，低阈值机械感受器输入会激活PKCγ神经元，从而将信息转发至二阶伤害感受性神经元，从而将触觉输入转化为疼痛。有几种机制可能有助于打开此门，包括抑制作用，激活局部星形胶质细胞，释放可扩散因子（例如活性氧），5-HT2A 5-羟色胺受体对PKCγ神经元的5-羟色胺能下降控制的改变和改变。因此，背角PKCγ神经元似乎是缓解慢性疼痛期间机械性异常性疼痛的相关治疗靶标。