We continue to examine the cellular basis of somatosensation and the molecules that are important in signaling and transmitting neural signals from peripheral sensory nerves. In the past year we have worked on neurons that express the ion-channel TRPV1 and the key molecules they contain. In this reporting period we investigated nerves that innervate the lung and how they are involved in airway hyperactivity in a rodent model for asthma. Our studies determined that TRPV1-neurons are required for lung hypersensitivity. In particular, elimination of, or activation of, vagal TRPV1-neurons either ablated, or potentiated asthma like responses. In another study, we addressed a controversy about the primary pruriceptive transmitter. We used RNAseq of tissue collected from mouse, rat and human to determine all genes expressed in the sensory nerves and the spinal cord. Our studies demonstrated that the neuropeptide GRP is found in the spinal cord, but not dorsal root ganglia of sensory neurons from each species, showing that GRP cannot be responsible for transmitting signal at the first synapse of the itch circuit resolving the issue of the contribution this peptide makes to itch. This study also confirmed that human tissues expresses the same itch specific neuropeptides and their receptors as those found in mouse, suggesting that a very similar itch transmission pathway is used in man. Additional screens of RNAseq data revealed a number of other novel signaling molecules and at present we are studying the physiological role of these genes. Lastly, we have embarked on projects aimed at determining the molecular mechanisms employed by touch sensitive cells in the detection of mechanical force.

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8
Fiscal Year
2014
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Dental & Craniofacial Research
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Huang, Jing; Polgár, Erika; Solinski, Hans Jürgen et al. (2018) Circuit dissection of the role of somatostatin in itch and pain. Nat Neurosci 21:707-716
Szczot, Marcin; Pogorzala, Leah A; Solinski, Hans Jürgen et al. (2017) Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction. Cell Rep 21:2760-2771
Pandey, Mritunjay; Zhang, Jian-Hua; Mishra, Santosh K et al. (2017) A central role for R7bp in the regulation of itch sensation. Pain 158:931-944
Ran, Chen; Hoon, Mark A; Chen, Xiaoke (2016) The coding of cutaneous temperature in the spinal cord. Nat Neurosci 19:1201-9
Hoon, Mark A (2015) Molecular dissection of itch. Curr Opin Neurobiol 34:61-6
Mishra, Santosh K; Hoon, Mark A (2015) Transmission of pruriceptive signals. Handb Exp Pharmacol 226:151-62
Goswami, Samridhi C; Mishra, Santosh K; Maric, Dragan et al. (2014) Molecular signatures of mouse TRPV1-lineage neurons revealed by RNA-Seq transcriptome analysis. J Pain 15:1338-1359
Tränkner, Dimitri; Hahne, Nadeau; Sugino, Ken et al. (2014) Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways. Proc Natl Acad Sci U S A 111:11515-20
Bautista, Diana M; Wilson, Sarah R; Hoon, Mark A (2014) Why we scratch an itch: the molecules, cells and circuits of itch. Nat Neurosci 17:175-82
Goswami, Samridhi C; Thierry-Mieg, Danielle; Thierry-Mieg, Jean et al. (2014) Itch-associated peptides: RNA-Seq and bioinformatic analysis of natriuretic precursor peptide B and gastrin releasing peptide in dorsal root and trigeminal ganglia, and the spinal cord. Mol Pain 10:44

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