Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury

被引:103
作者
Peirs, Cedric [1 ,2 ,5 ]
Williams, Sean-Paul G. [1 ,2 ]
Zhao, Xinyi [1 ,2 ,6 ]
Arokiaraj, Cynthia M. [1 ,2 ]
Ferreira, David W. [1 ,2 ]
Noh, Myung-chul [1 ,2 ]
Smith, Kelly M. [1 ,2 ]
Halder, Priyabrata [1 ,2 ]
Corrigan, Kelly A. [1 ,2 ]
Gedeon, Jeremy Y. [1 ,2 ]
Lee, Suh Jin [1 ,2 ]
Gatto, Graziana [3 ]
Chi, David [4 ]
Ross, Sarah E. [1 ,2 ]
Goulding, Martyn [3 ]
Seal, Rebecca P. [1 ,2 ,4 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Sch Med, Pittsburgh Ctr Pain Res, Pittsburgh, PA 15260 USA
[3] Salk Inst Biol Studies, Mol Neurobiol Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA
[4] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15260 USA
[5] Univ Clermont Auvergne, CHU, INSERM, NeuroDol, F-63000 Clermont Ferrand, France
[6] Tsinghua Univ, Dept Neurol, Beijing Tsinghua Changgung Hosp, Sch Med, Beijing 102218, Peoples R China
关键词
SPARED NERVE INJURY; KINASE-C-GAMMA; NEUROPATHIC PAIN; EXPRESSING NEURONS; MICE LACKING; TOUCH; INTERNEURONS; MODEL; GATE; IDENTIFICATION;
D O I
10.1016/j.neuron.2020.10.027
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The spinal dorsal horn is a major site for the induction and maintenance of mechanical allodynia, but the circuitry that underlies this clinically important form of pain remains unclear. The studies presented here provide strong evidence that the neural circuits conveying mechanical allodynia in the dorsal horn differ by the nature of the injury. Calretinin (CR) neurons in lamina II inner convey mechanical allodynia induced by inflammatory injuries, while protein kinase C gamma (PKC gamma) neurons at the lamina II/III border convey mechanical allodynia induced by neuropathic injuries. Cholecystokinin (CCK) neurons located deeper within the dorsal horn (laminae III-IV) are important for both types of injuries. Interestingly, the Maf(+) subset of CCK neurons is composed of transient vesicular glutamate transporter 3 (tVGLUT3) neurons, which convey primarily dynamic allodynia. Identification of an etiology-based circuitry for mechanical allodynia in the dorsal horn has important implications for the mechanistic and clinical understanding of this condition.
引用
收藏
页码:73 / 90.e7
页数:26
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