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Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors

Author

Listed:
  • Devin M. Barry

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Xue-Ting Liu

    (Washington University School of Medicine
    Washington University School of Medicine
    Guangzhou Medical University)

  • Benlong Liu

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Xian-Yu Liu

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Fang Gao

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Xiansi Zeng

    (Washington University School of Medicine
    Washington University School of Medicine
    Xinyang Normal University)

  • Juan Liu

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Qianyi Yang

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Steven Wilhelm

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Jun Yin

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Ailin Tao

    (Washington University School of Medicine
    Guangzhou Medical University)

  • Zhou-Feng Chen

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

Abstract

Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role of GRP in sensory neurons, we generated a floxed Grp mouse line. We found that conditional knockout of Grp in sensory neurons results in attenuated non-histaminergic itch, without impairing histamine-induced itch. Using a Grp-Cre knock-in mouse line, we show that the upper epidermis of the skin is exclusively innervated by GRP fibers, whose activation via optogeneics and chemogenetics in the skin evokes itch- but not pain-related scratching or wiping behaviors. In contrast, intersectional genetic ablation of spinal Grp neurons does not affect itch nor pain transmission, demonstrating that spinal Grp neurons are dispensable for itch transmission. These data indicate that GRP is a neuropeptide in sensory neurons for non-histaminergic itch, and GRP sensory neurons are dedicated to itch transmission.

Suggested Citation

  • Devin M. Barry & Xue-Ting Liu & Benlong Liu & Xian-Yu Liu & Fang Gao & Xiansi Zeng & Juan Liu & Qianyi Yang & Steven Wilhelm & Jun Yin & Ailin Tao & Zhou-Feng Chen, 2020. "Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15230-y
    DOI: 10.1038/s41467-020-15230-y
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    Cited by:

    1. Kensho Kanehisa & Keisuke Koga & Sho Maejima & Yuto Shiraishi & Konatsu Asai & Miho Shiratori-Hayashi & Mei-Fang Xiao & Hirotaka Sakamoto & Paul F. Worley & Makoto Tsuda, 2022. "Neuronal pentraxin 2 is required for facilitating excitatory synaptic inputs onto spinal neurons involved in pruriceptive transmission in a model of chronic itch," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Hyoung-Gon Ko & Hyunsu Jung & Seunghyo Han & Dong Il Choi & Chiwoo Lee & Ja Eun Choi & Jihae Oh & Chuljung Kwak & Dae Hee Han & Jun-Nyeong Kim & Sanghyun Ye & Jiah Lee & Jaehyun Lee & Kyungmin Lee & J, 2025. "Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice," Nature Communications, Nature, vol. 16(1), pages 1-16, December.

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