Identification of Spinal Circuits Transmitting and Gating Mechanical Pain

被引:423
作者
Duan, Bo [1 ,2 ]
Cheng, Longzhen [1 ,2 ,8 ,9 ]
Bourane, Steeve [3 ]
Britz, Olivier [3 ]
Padilla, Christopher [3 ]
Garcia-Campmany, Lidia [3 ,4 ,5 ]
Krashes, Michael [4 ,5 ]
Knowlton, Wendy [1 ,2 ]
Velasquez, Tomoko [3 ]
Ren, Xiangyu
Ross, Sarah E. [6 ,7 ]
Lowell, Bradford B. [4 ,5 ]
Wang, Yun [8 ,9 ]
Goulding, Martyn [3 ]
Ma, Qiufu [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[3] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA
[4] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA
[5] Harvard Univ, Sch Med, Boston, MA 02215 USA
[6] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA
[7] Univ Pittsburgh, Pain Ctr, Pittsburgh, PA 15213 USA
[8] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China
[9] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
SUBSTANTIA-GELATINOSA NEURONS; SUPERFICIAL DORSAL-HORN; MARGINAL ZONE; GABAERGIC NEURONS; THERMAL STIMULI; SENSORY NEURONS; CELLULAR BASIS; CORD; HYPERALGESIA; GATE;
D O I
10.1016/j.cell.2014.11.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pain information processing in the spinal cord has been postulated to rely on nociceptive transmission (T) neurons receiving inputs from nociceptors and A beta mechanoreceptors, with A beta inputs gated through feed-forward activation of spinal inhibitory neurons (INs). Here, we used intersectional genetic manipulations to identify these critical components of pain transduction. Marking and ablating six populations of spinal excitatory and inhibitory neurons, coupled with behavioral and electrophysiological analysis, showed that excitatory neurons expressing somatostatin (SOM) include T-type cells, whose ablation causes loss of mechanical pain. Inhibitory neurons marked by the expression of dynorphin (Dyn) represent INs, which are necessary to gate A beta fibers from activating SOM+ neurons to evoke pain. Therefore, peripheral mechanical nociceptors and A beta mechanoreceptors, together with spinal SOM+ excitatory and Dyn(+) inhibitory neurons, form a microcircuit that transmits and gates mechanical pain.
引用
收藏
页码:1417 / 1432
页数:16
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