Somatosensation and pain

神经病理性疼痛涉及到一种深刻的敏感度开关，以至于低强度的输入会产生疼痛。与伤害性疼痛不同，神经性疼痛实际上是一种对正常疼痛专一性模式的破坏。临床上，周围神经病理性疼痛广泛存在于周围神经损伤、中毒性和代谢性神经病以及带状疱疹和艾滋病等病毒感染性疾病的患者中。遗憾的是，传统的止痛药在治疗神经病理性疼痛时往往效果不佳。 目前，已有多种机制独立或共同促进神经病理性疼痛：中枢敏化、去抑制和中枢传入终末萌发。然而，脊椎-大脑沟通如何以及是否参与神经病理性疼痛仍然知之甚少。在我们之前的研究中，我们表明皮质脊髓神经元是控制触觉和机械痛觉过敏所必需的，从而证明了第一例来自皮质的直接自上而下的控制(Liu等人，《自然》，2018)。这个项目是先前研究的自然延伸。利用电生理学、单细胞测序和成像技术，我们探索了参与双向心身交流的自上而下和自下而上的电路，并试图破译它们在调节触觉和神经病理性疼痛敏感性方面的作用。通过进一步剖析参与躯体感觉和疼痛控制的神经回路，我们的研究揭示了疼痛超敏的潜在机制，并设计了治疗疼痛的新的治疗干预措施。

Neuropathic pain involves a profound switch in sensitivity such that low-intensity input can generate pain. Different from nociceptive pain, neuropathic pain is indeed a disruption of the normal pattern of pain specificity. Clinically, peripheral neuropathic pain is widely present in patients suffering from peripheral nerve trauma, toxic and metabolic neuropathies, and viral infectious diseases such as Herpes zoster and AIDS. Unfortunately, traditional anti-pain medicines often fail to show satisfactory effects in treating neuropathic pain. Currently, a number of mechanisms have been postulated, either independently or together, to promote neuropathic pain: central sensitization, disinhibition, and central afferent terminal sprouting. However, how and whether spino-brain communication is involved in neuropathic pain remains poorly understood. In our previous studies, we showed that the corticospinal neurons are required for controlling both tactile and mechanical allodynia sensitivity and thereby demonstrated a first case of a direct top-down control from the cortex (Liu et al., Nature, 2018). This project is a natural extension of previous studies. With electrophysiology, single cell sequencing and imaging techniques, we explored both top-down and bottom-up circuits involved in bi-directional mind-body communication and are trying to decipher their roles in regulating tactile and neuropathic pain sensitivity. By further dissection of neural circuits involved in somatosensation and pain control, our studies shed light on the underlying mechanisms of pain hypersensitivity and design of novel therapeutic interventions to treat pain.