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Papers: 13 Mar 2021 - 19 Mar 2021

2021 Mar 16

Sci Signal



Editor's Pick

A ligand-receptor interactome platform for discovery of pain mechanisms and therapeutic targets.


Wangzhou A, Paige C, Neerukonda SV, Naik DK, Kume M, David ET, Dussor G, Ray PR, Price TJ
Sci Signal. 2021 Mar 16; 14(674).
PMID: 33727337.


In the peripheral nervous system, ligand-receptor interactions between cells and neurons shape sensory experience, including pain. We set out to identify the potential interactions between sensory neurons and peripheral cell types implicated in disease-associated pain. Using mouse and human RNA sequencing datasets and computational analysis, we created interactome maps between dorsal root ganglion (DRG) sensory neurons and an array of normal cell types, as well as colitis-associated glial cells, rheumatoid arthritis-associated synovial macrophages, and pancreatic tumor tissue. These maps revealed a common correlation between the abundance of heparin-binding EGF-like growth factor (HBEGF) in peripheral cells with that of its receptor EGFR (a member of the ErbB family of receptors) in DRG neurons. Subsequently, we confirmed that increased abundance of HBEGF enhanced nociception in mice, likely acting on DRG neurons through ErbB family receptors. Collectively, these interactomes highlight ligand-receptor interactions that may lead to treatments for disease-associated pain and, furthermore, reflect the complexity of cell-to-neuron signaling in chronic pain states.