4.8 Article

Distinct neural networks derived from galanin-containing nociceptors and neurotensin-expressing pruriceptors

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2118501119

Keywords

pain; itch; neural network; dorsal root ganglia; herpes simplex virus

Funding

  1. National Natural Science Foundation of China [32192413, 31600853, 32071001, 32030050, 32192412, 81827901]
  2. Special Fund for Science-Technology Innovation Strategy of Guangdong Province [2021B0909050004]
  3. Chinese Academy of Sciences [QYZDYSSWSMC007]
  4. Strategic Priority Research Program of the Chinese Academy of Sciences [XDB39050100]
  5. Science and Technology Commission of Shanghai Municipality [18JC1420301]
  6. Science and Technology Planning Project of Guangdong Province [2018B030331001]
  7. Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences [2019-I2M-5-082]

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We reveal the organization of neural networks in a DRG neuron type-dependent manner for processing pain and itch.
Pain and itch are distinct sensations arousing evasion and compulsive desire for scratching, respectively. It's unclear whether they could invoke different neural networks in the brain. Here, we use the type 1 herpes simplex virus H129 strain to trace the neural networks derived from two types of dorsal root ganglia (DRG) neurons: one kind of polymodal nociceptors containing galanin (Gal) and one type of pruriceptors expressing neurotensin (Nts). The DRG microinjection and immunosuppression were performed in transgenic mice to achieve a successful tracing from specific types of DRG neurons to the primary sensory cortex. About one-third of nuclei in the brain were labeled. More than half of them were differentially labeled in two networks. For the ascending pathways, the spinothalamic tract was absent in the network derived from Nts-expressing pruriceptors, and the two networks shared the spinobulbar projections but occupied different subnuclei. As to the motor systems, more neurons in the primary motor cortex and red nucleus of the somatic motor system participated in the Gal-containing nociceptor-derived network, while more neurons in the nucleus of the solitary tract (NST) and the dorsal motor nucleus of vagus nerve (DMX) of the emotional motor system was found in the Nts-expressing pruriceptor-derived network. Functional validation of differentially labeled nuclei by c-Fos test and chemogenetic inhibition suggested the red nucleus in facilitating the response to noxious heat and the NST/DMX in regulating the histamine-induced scratching. Thus, we reveal the organization of neural networks in a DRG neuron type-dependent manner for processing pain and itch.

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