Synchronized cluster firing, a distinct form of sensory neuron activation, drives spontaneous pain.
Synchronized cluster firing, a distinct form of sensory neuron activation, drives spontaneous pain.
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DOI：
10.1016/j.neuron.2021.10.019
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发表时间：
2022-01-19
期刊：
影响因子：
16.2
通讯作者：
Dong X
中科院分区：
文献类型：
--
作者：
Zheng Q;Xie W;Lückemeyer DD;Lay M;Wang XW;Dong X;Limjunyawong N;Ye Y;Zhou FQ;Strong JA;Zhang JM;Dong X
自发性疼痛是指在没有外部刺激的情况下发生的疼痛。它是慢性疼痛的主要症状，治疗困难，而且对自发性疼痛的机制知之甚少。在这里，我们采用背根神经节（DRG）神经元的体内成像，并发现了一种不同形式的异常自发活动后，周围神经损伤：集群的相邻DRG神经元发射同步和零星。簇放电水平与神经损伤诱发的自发痛行为直接相关。此外，我们证明了簇放电是由交感神经的活动触发的，交感神经在损伤后发芽进入DRG，并确定去甲肾上腺素是介导这种独特放电的关键神经递质。交感神经活性和去甲肾上腺素受体的化学发生学和药理学操作表明，它们对于DRG簇放电和自发性疼痛行为都是必要的和充分的。因此，阻断交感神经介导的簇放电可能代表治疗自发性疼痛的新范例。自发性疼痛是神经病理性疼痛患者的主要主诉，但对其了解甚少。Zheng等人描述了一种新形式的感觉神经元活动：空间聚集的感觉神经元零星地一起放电，其在小鼠神经性疼痛模型中介导自发性疼痛。交感神经纤维不正常地发芽进入感觉神经节是这种簇放电的基础。
Spontaneous pain refers to pain occurring without external stimuli. It is a primary complaint in chronic pain conditions and remains difficult to treat. Moreover, the mechanisms underlying spontaneous pain remain poorly understood. Here, we employed in vivo imaging of dorsal root ganglion (DRG) neurons and discovered a distinct form of abnormal spontaneous activity following peripheral nerve injury: clusters of adjacent DRG neurons firing synchronously and sporadically. The level of cluster firing directly correlated with nerve injury induced spontaneous pain behaviors. Furthermore, we demonstrated that cluster firing is triggered by activity of sympathetic nerves, which sprout into DRG after injury, and identified norepinephrine as a key neurotransmitter mediating this unique firing. Chemogenetic and pharmacological manipulations of sympathetic activity and norepinephrine receptors suggest that they are both necessary and sufficient for DRG cluster firing and spontaneous pain behavior. Therefore, blocking sympathetic-mediated cluster firing may represent a new paradigm in treating spontaneous pain. Spontaneous pain, a primary complaint of neuropathic pain patients, is poorly understood. Zheng et al. describe a new form of sensory neuron activity: spatially clustered sensory neurons sporadically firing together, that mediates spontaneous pain in mice neuropathic pain models. Sympathetic fibers abnormally sprouting into sensory ganglia underlie this cluster firing.
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DOI：
10.1126/science.1169096
发表时间：
2009-02-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kuchibhotla KV;Lattarulo CR;Hyman BT;Bacskai BJ
通讯作者：
Bacskai BJ
影响因子：
1.7
作者：
Cho, HJ;Kim, DS;Kim, KJ
通讯作者：
Kim, KJ
DOI：
10.1073/pnas.1011221107
发表时间：
2010-09-07
影响因子：
11.1
作者：
Guan, Yun;Liu, Qin;Dong, Xinzhong
通讯作者：
Dong, Xinzhong
影响因子：
16.2
作者：
Feng, Jiesi;Zhang, Changmei;Li, Yulong
通讯作者：
Li, Yulong
影响因子：
3.4
作者：
Chisholm, Kim I.;Khovanov, Nikita;McMahon, Stephen B.
通讯作者：
McMahon, Stephen B.