SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons

被引：119

作者：

Han, Qingjian ^{[1
]}

Kim, Yong Ho ^{[1
]}

Wang, Xiaoming ^{[2
]}

Liu, Di ^{[1
]}

Zhang, Zhi-Jun ^{[1
]}

Bey, Alexandra L. ^{[3
]}

Lay, Mark ^{[1
]}

Chang, Wonseok ^{[1
]}

Berta, Temugin ^{[1
]}

Zhang, Yan ^{[1
]}

Jiang, Yong-Hui ^{[2
,3
]}

Ji, Ru-Rong ^{[1
,3
]}

机构：

[1] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA

来源：

NEURON | 2016年 / 92卷 / 06期

关键词：

MECHANICAL ALLODYNIA; MICE LACKING; AUTISM; PAIN; RECEPTOR; MUTATIONS; CHILDREN; DYSFUNCTION; NOCICEPTION; INHIBITION;

D O I：

10.1016/j.neuron.2016.11.007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Abnormal pain sensitivity is commonly associated with autism spectrum disorders (ASDs) and affects the life quality of ASD individuals. SHANK3 deficiency was implicated in ASD and pain dysregulation. Here, we report functional expression of SHANK3 in mouse dorsal root ganglion (DRG) sensory neurons and spinal cord presynaptic terminals. Homozygous and heterozygous Shank3 complete knockout (Delta e4-22) results in impaired heat hyperalgesia in inflammatory and neuropathic pain. Specific deletion of Shank3 in Nav1.8-expressing sensory neurons also impairs heat hyperalgesia in homozygous and heterozygous mice. SHANK3 interacts with transient receptor potential subtype V1 (TRPV1) via Proline-rich region and regulates TRPV1 surface expression. Furthermore, capsaicin-induced spontaneous pain, inward currents in DRG neurons, and synaptic currents in spinal cord neurons are all reduced after Shank3 haploinsufficiency. Finally, partial knockdown of SHANK3 expression in human DRG neurons abrogates TRPV1 function. Our findings reveal a peripheral mechanism of SHANK3, which may underlie pain deficits in SHANK3-related ASDs.

引用

页码：1279 / 1293

页数：15

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