Format

Send to

Choose Destination
Neuron. 2016 Sep 7;91(5):1137-1153. doi: 10.1016/j.neuron.2016.07.038. Epub 2016 Aug 18.

Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain.

Author information

1
Department of Neuroscience, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Department of Anesthesiology, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, USA.
3
Department of Anesthesiology, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, USA. Electronic address: yuanxiang.tao@njms.rutgers.edu.
4
Department of Neuroscience, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: luow@mail.med.upenn.edu.

Abstract

The gate control theory (GCT) of pain proposes that pain- and touch-sensing neurons antagonize each other through spinal cord dorsal horn (DH) gating neurons. However, the exact neural circuits underlying the GCT remain largely elusive. Here, we identified a new population of deep layer DH (dDH) inhibitory interneurons that express the receptor tyrosine kinase Ret neonatally. These early RET+ dDH neurons receive excitatory as well as polysynaptic inhibitory inputs from touch- and/or pain-sensing afferents. In addition, they negatively regulate DH pain and touch pathways through both pre- and postsynaptic inhibition. Finally, specific ablation of early RET+ dDH neurons increases basal and chronic pain, whereas their acute activation reduces basal pain perception and relieves inflammatory and neuropathic pain. Taken together, our findings uncover a novel spinal circuit that mediates crosstalk between touch and pain pathways and suggest that some early RET+ dDH neurons could function as pain "gating" neurons.

PMID:
27545714
PMCID:
PMC5017914
DOI:
10.1016/j.neuron.2016.07.038
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center