神经病理性疼痛
去抑制
SNi公司
神经科学
痛觉超敏
脊髓
神经损伤
抑制性突触后电位
医学
伤害
慢性疼痛
敏化
痛觉过敏
化学
受体
生物
内科学
水解
生物化学
酸水解
作者
Bing Cao,Grégory Scherrer,Lu Chen
出处
期刊:Neuron
[Elsevier]
日期:2022-12-01
卷期号:110 (24): 4108-4124.e6
被引量:9
标识
DOI:10.1016/j.neuron.2022.09.027
摘要
Central sensitization caused by spinal disinhibition is a key mechanism of mechanical allodynia in neuropathic pain. However, the molecular mechanisms underlying spinal disinhibition after nerve injury remain unclear. Here, we show in mice that spared nerve injury (SNI), which induces mechanical hypersensitivity and neuropathic pain, triggers homeostatic reduction of inhibitory outputs from dorsal horn parvalbumin-positive (PV+) interneurons onto both primary afferent terminals and excitatory interneurons. The reduction in inhibitory outputs drives hyperactivation of the spinal cord nociceptive pathway, causing mechanical hypersensitivity. We identified the retinoic acid receptor RARα, a central regulator of homeostatic plasticity, as the key molecular mediator for this synaptic disinhibition. Deletion of RARα in spinal PV+ neurons or application of an RARα antagonist in the spinal cord prevented the development of SNI-induced mechanical hypersensitivity. Our results identify RARα as a crucial molecular effector for neuropathic pain and a potential target for its treatment.
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