Cortical Signature and Modulation of Pain

皮层信号与疼痛的调制 摘要/项目摘要 疼痛知觉包括两个主要维度：感觉-辨别维度和情感-认知维度 方面在这个建议中，我们将集中在皮层签名和调制的感觉方面， 疼痛的小鼠模型。疼痛可大致分为炎症性疼痛或神经性疼痛。一个共同 这两种类型的疼痛的条件是机械性异常性疼痛：外部应用无害的温柔触摸变得 痛.奇怪的是，疼痛激发了自我启动的恢复行为，如摩擦和按摩的皮肤。 疼痛区域;并且来自这种自发行为的机械刺激通常减轻疼痛。的 外部与自我施加的机械刺激的相反效应的神经回路机制 对疼痛状况的了解仍然很少。根据以前的研究以及我们的初步研究， 我们假设，来自初级躯体感觉（S1）皮质的皮质脊髓投射神经元促进 疼痛模型中的机械超敏反应，而特定的运动皮层投射神经元起关键作用 在自我启动的恢复性行为（如小鼠的舔和擦拭）中抑制触觉异常性疼痛。 我们进一步假设，皮层疼痛信号可以从大的活动模式中读出。 单个S1神经元的群体，通过比较它们在疼痛与非疼痛或疼痛中的活动， 解除条件。我们将在体内使用特定皮质神经元的病毒遗传标记组合 钙成像和体内多电极细胞外记录在自由行为的小鼠，光遗传学- 辅助切片生理学，光学/化学遗传学操作和计算分析，以测试我们的 假设

Cortical Signature and Modulation of Pain Abstract/Project Summary Pain perception contains two main dimensions: the sensory-discriminative and the affective-cognitive aspects. In this proposal, we will focus on the cortical signature and modulations of the sensory aspects of pain using mouse models. Pain can be largely divided into inflammatory or neuropathic pain. A common condition in both types of pain is mechanical allodynia: externally applied innocuous gentle touch becomes painful. Paradoxically, pain elicits self-initiated recuperative behaviors such as rubbing and massaging of the painful regions; and the mechanical stimuli from such self-generated behaviors generally relieve pain. The neural circuit mechanisms underlying the opposite effects of external versus self-applied mechanical stimuli in pain conditions remain poorly understood. Based on previous research as well as our preliminary studies, we hypothesize that corticospinal projecting neurons from primary somatosensory (S1) cortex facilitate mechanical hypersensitivity in pain models, whereas specific motor cortex projection neurons play key roles in suppressing tactile allodynia in self-initiated recuperative behaviors (such as licking and wiping in mice). We further hypothesize that the cortical pain signature can be read out from activity patterns of large populations of individual S1 neurons by comparing their activities in the painful versus non-painful or pain- relieved conditions. We will use a combination of viral-genetic labeling of specific cortical neurons, in vivo calcium imaging and in vivo multi-electrode extracellular recording in freely behaving mice, optogenetics- assisted slice physiology, opto/chemicogenetic manipulations, and computational analyses to test our hypotheses.