Somatosensation and pain

神经性疼痛涉及敏感性的深刻转变，使得低强度输入可以产生疼痛。与伤害性疼痛不同，神经病理性疼痛确实是对疼痛特异性正常模式的破坏。在临床上，周围神经性疼痛广泛存在于患有周围神经创伤、毒性和代谢性神经病以及病毒感染性疾病如带状疱疹和艾滋病的患者中。不幸的是，传统的抗疼痛药物在治疗神经性疼痛方面往往不能显示出令人满意的效果。 目前，许多机制已被假定，无论是独立或共同，以促进神经性疼痛：中枢敏化，去抑制，和中央传入终末发芽。然而，自上而下的控制如何以及是否参与神经性疼痛仍然知之甚少。在我们以前的研究中，我们表明皮质脊髓神经元是控制触觉和机械异常性疼痛敏感性所必需的，从而证明了来自皮质的直接自上而下控制的第一例（Liu等人，Nature，2018）。该项目是以前研究的自然延伸。通过电生理学、单细胞测序和成像技术，我们探索了皮质脊髓神经元的上游和下游靶点，并试图破译它们在调节触觉和神经病理性疼痛敏感性中的作用。通过进一步解剖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反应的潜在机制和治疗疼痛的新型治疗干预措施的设计。

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 top-down control 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 up-stream and down-stream targets of corticospinal neurons 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 study shed light into the underlying mechanisms of pain hypersensitivity and design of novel therapeutic interventions to treat pain.