Neuronal pentraxin 2 is required for facilitating excitatory synaptic inputs onto spinal neurons involved in pruriceptive transmission in a model of chronic itch

Kensho Kanehisa, Keisuke Koga, Sho Maejima, Yuto Shiraishi, Konatsu Asai, Miho Shiratori-Hayashi, Mei-Fang Xiao, Hirotaka Sakamoto, Paul F. Worley and Makoto Tsuda ()
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Kensho Kanehisa: Kyushu University
Keisuke Koga: Kyushu University
Sho Maejima: Okayama University, 130-17 Kashino
Yuto Shiraishi: Kyushu University
Konatsu Asai: Kyushu University
Miho Shiratori-Hayashi: Kyushu University
Mei-Fang Xiao: Johns Hopkins University School of Medicine
Hirotaka Sakamoto: Okayama University, 130-17 Kashino
Paul F. Worley: Johns Hopkins University School of Medicine
Makoto Tsuda: Kyushu University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract An excitatory neuron subset in the spinal dorsal horn (SDH) that expresses gastrin-releasing peptide receptors (GRPR) is critical for pruriceptive transmission. Here, we show that glutamatergic excitatory inputs onto GRPR+ neurons are facilitated in mouse models of chronic itch. In these models, neuronal pentraxin 2 (NPTX2), an activity-dependent immediate early gene product, is upregulated in the dorsal root ganglion (DRG) neurons. Electron microscopy reveals that NPTX2 is present at presynaptic terminals connected onto postsynaptic GRPR+ neurons. NPTX2-knockout prevents the facilitation of synaptic inputs to GRPR+ neurons, and repetitive scratching behavior. DRG-specific NPTX2 expression rescues the impaired behavioral phenotype in NPTX2-knockout mice. Moreover, ectopic expression of a dominant-negative form of NPTX2 in DRG neurons reduces chronic itch-like behavior in mice. Our findings indicate that the upregulation of NPTX2 expression in DRG neurons contributes to the facilitation of glutamatergic inputs onto GRPR+ neurons under chronic itch-like conditions, providing a potential therapeutic target.

Date: 2022
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DOI: 10.1038/s41467-022-30089-x

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