Cortical Signature and Modulation of Pain

皮层信号与痛觉调制 摘要/项目摘要 疼痛知觉包括两个主要维度：感觉辨别性和情感认知性 方面。在这项提案中，我们将重点介绍大脑皮质的信号和感觉方面的调节。 使用小鼠模型进行疼痛实验。疼痛在很大程度上可以分为炎症性或神经病理性疼痛。一种常见的 这两种疼痛的情况都是机械性超敏：外用无害的温柔触摸变成 很痛苦。矛盾的是，疼痛会引发自发的康复行为，如摩擦和按摩 疼痛区域；而这种自我产生的行为产生的机械刺激通常会缓解疼痛。这个 外部机械刺激与自身机械刺激相反效应的神经回路机制 疼痛的情况仍然知之甚少。根据之前的研究以及我们的初步研究， 我们假设初级躯体感觉(S1)皮层的皮质脊髓投射神经元 疼痛模型中的机械超敏反应，而特定的运动皮质投射神经元起关键作用 在抑制自主恢复行为(如小鼠舔和擦拭)中的触觉异常痛。 我们进一步假设，皮层疼痛信号可以从大脑皮层的活动模式中读出 通过比较疼痛和非疼痛或疼痛中的活动来观察单个S1神经元的数量。 被解除的条件。我们将在体内使用特定皮质神经元的病毒遗传标记的组合 自由行为小鼠的钙成像和活体多电极细胞外记录，光遗传学- 辅助切片生理学、光/化学遗传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.