Abstract：
Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.
摘要：
神经性疼痛，严重的临床症状,显著影响患者的生活质量。近几十年来，神经性疼痛的分子机制一直是研究的焦点；然而，与该疾病相关的神经元回路介导的机制仍然知之甚少。这里,我们报告说，从下丘脑外侧（LH）谷氨酸能神经元到外侧（LHb）的投影，兴奋性LH-LHb神经元回路,参与神经损伤引起的伤害性超敏反应。LH谷氨酸能神经元被激活，并在慢性收缩损伤后对正常非有害刺激表现出增强的反应。LH谷氨酸能神经元或兴奋性LH-LHb回路的化学遗传抑制阻断了CCI诱导的伤害性超敏反应。LH-LHb回路的激活导致无神经损伤的小鼠对机械和热刺激的反应增强。这些发现表明，LH神经元及其触发的LH-LHb回路参与了神经性疼痛的中枢机制，并且可能是治疗这种疾病的靶标。
