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Exploration of Sensory and Spinal Neurons Expressing GRP in Itch and Pain

56 Pages Posted: 15 Sep 2018 Sneak Peek Status: Review Complete

See all articles by Devin M. Barry

Devin M. Barry

Washington University in St. Louis - Center for the Study of Itch

Qianyi Yang

Washington University in St. Louis - Center for the Study of Itch

Xian-Yu Liu

Washington University in St. Louis - Center for the Study of Itch

Xue-Ting Liu

Washington University in St. Louis - Center for the Study of Itch

Xiansi Zeng

Washington University in St. Louis - Center for the Study of Itch

Ben-Long Liu

Washington University in St. Louis - Center for the Study of Itch

Zhou-Feng Chen

Washington University in St. Louis - Center for the Study of Itch

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Abstract

Gastrin-releasing peptide (GRP) is a putative itch-specific neurotransmitter, but definite evidence in the dorsal root ganglion (DRG) and spinal cord is lacking. We generated and validated a Grp-Cre knock-in (GrpCre-KI) mouse line whereby Grp neurons are genetically labeled. Cre-dependent marking analysis revealed exclusive innervation of the upper epidermis of the skin by GRP fibers. Importantly, optical stimulation of Grp fibers expressing channel rhodopsin (ChR2) in the skin evoked itch but not pain-related scratching behaviors, while conditional deletion of Grp in sensory neurons attenuated non-histaminergic itch. In contrast, intersectional genetic ablation of spinal Grp neurons did not affect itch nor pain transmission. Our study demonstrates a role of GRP in sensory neurons in itch and suggests that GRP sensory neurons are dedicated to itch transmission. GrpCre-KI mice provide a long-sought avenue for investigating peripheral coding mechanism of itch and further interrogation of itch-nerve fibers in the skin under chronic pruritus.

Suggested Citation

Barry, Devin M. and Yang, Qianyi and Liu, Xian-Yu and Liu, Xue-Ting and Zeng, Xiansi and Liu, Ben-Long and Chen, Zhou-Feng, Exploration of Sensory and Spinal Neurons Expressing GRP in Itch and Pain (September 14, 2018). Available at SSRN: https://ssrn.com/abstract=3249821 or http://dx.doi.org/10.2139/ssrn.3249821
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Devin M. Barry

Washington University in St. Louis - Center for the Study of Itch

One Brookings Drive
Campus Box 1208
St. Louis, MO 63130-4899
United States

Qianyi Yang

Washington University in St. Louis - Center for the Study of Itch

One Brookings Drive
Campus Box 1208
St. Louis, MO 63130-4899
United States

Xian-Yu Liu

Washington University in St. Louis - Center for the Study of Itch

One Brookings Drive
Campus Box 1208
St. Louis, MO 63130-4899
United States

Xue-Ting Liu

Washington University in St. Louis - Center for the Study of Itch

One Brookings Drive
Campus Box 1208
St. Louis, MO 63130-4899
United States

Xiansi Zeng

Washington University in St. Louis - Center for the Study of Itch

One Brookings Drive
Campus Box 1208
St. Louis, MO 63130-4899
United States

Ben-Long Liu

Washington University in St. Louis - Center for the Study of Itch

One Brookings Drive
Campus Box 1208
St. Louis, MO 63130-4899
United States

Zhou-Feng Chen (Contact Author)

Washington University in St. Louis - Center for the Study of Itch ( email )

One Brookings Drive
Campus Box 1208
St. Louis, MO 63130-4899
United States

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