Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain

Takahiro Masuda, Yui Ozono, Satsuki Mikuriya, Yuta Kohro, Hidetoshi Tozaki-Saitoh, Ken Iwatsuki, Hisayuki Uneyama, Reiko Ichikawa, Michael W. Salter, Makoto Tsuda () and Kazuhide Inoue ()
Additional contact information
Takahiro Masuda: Graduate School of Pharmaceutical Sciences, Kyushu University
Yui Ozono: Graduate School of Pharmaceutical Sciences, Kyushu University
Satsuki Mikuriya: Graduate School of Pharmaceutical Sciences, Kyushu University
Yuta Kohro: Graduate School of Pharmaceutical Sciences, Kyushu University
Hidetoshi Tozaki-Saitoh: Graduate School of Pharmaceutical Sciences, Kyushu University
Ken Iwatsuki: Institute for Innovation, Ajinomoto Co., Inc.
Hisayuki Uneyama: Institute for Innovation, Ajinomoto Co., Inc.
Reiko Ichikawa: Institute for Innovation, Ajinomoto Co., Inc.
Michael W. Salter: Program in Neurosciences & Mental Health, Hospital for Sick Children
Makoto Tsuda: Graduate School of Pharmaceutical Sciences, Kyushu University
Kazuhide Inoue: Graduate School of Pharmaceutical Sciences, Kyushu University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing ATP within the spinal cord after PNI is unknown. Here we show that PNI increases expression of vesicular nucleotide transporter (VNUT) in the spinal cord. Extracellular ATP content ([ATP]e) within the spinal cord was increased after PNI, and this increase was suppressed by exocytotic inhibitors. Mice lacking VNUT did not show PNI-induced increase in [ATP]e and had attenuated hypersensitivity. These phenotypes were recapitulated in mice with specific deletion of VNUT in spinal dorsal horn (SDH) neurons, but not in mice lacking VNUT in primary sensory neurons, microglia or astrocytes. Conversely, ectopic VNUT expression in SDH neurons of VNUT-deficient mice restored PNI-induced increase in [ATP]e and pain. Thus, VNUT is necessary for exocytotic ATP release from SDH neurons which contributes to neuropathic pain.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms12529 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12529

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12529

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().