% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Vicua:127706,
author = {L. Vicuña and D. E. Strochlic and A. Latremoliere and K.
K. Bali and M. Simonetti and D. Husainie and S. Prokosch$^*$
and P. Riva and R. S. Griffin and C. Njoo and S. Gehrig and
M. A. Mall and B. Arnold$^*$ and M. Devor and C. J. Woolf
and S. D. Liberles and M. Costigan and R. Kuner},
title = {{T}he serine protease inhibitor {S}erpin{A}3{N} attenuates
neuropathic pain by inhibiting {T} cell-derived leukocyte
elastase.},
journal = {Nature medicine},
volume = {21},
number = {5},
issn = {1546-170X},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DKFZ-2017-03729},
pages = {518 - 523},
year = {2015},
abstract = {Neuropathic pain is a major, intractable clinical problem
and its pathophysiology is not well understood. Although
recent gene expression profiling studies have enabled the
identification of novel targets for pain therapy, classical
study designs provide unclear results owing to the
differential expression of hundreds of genes across sham and
nerve-injured groups, which can be difficult to validate,
particularly with respect to the specificity of pain
modulation. To circumvent this, we used two outbred lines of
rats, which are genetically similar except for being
genetically segregated as a result of selective breeding for
differences in neuropathic pain hypersensitivity. SerpinA3N,
a serine protease inhibitor, was upregulated in the dorsal
root ganglia (DRG) after nerve injury, which was further
validated for its mouse homolog. Mice lacking SerpinA3N
developed more neuropathic mechanical allodynia than
wild-type (WT) mice, and exogenous delivery of SerpinA3N
attenuated mechanical allodynia in WT mice. T lymphocytes
infiltrate the DRG after nerve injury and release leukocyte
elastase (LE), which was inhibited by SerpinA3N derived from
DRG neurons. Genetic loss of LE or exogenous application of
a LE inhibitor (Sivelastat) in WT mice attenuated
neuropathic mechanical allodynia. Overall, we reveal a novel
and clinically relevant role for a member of the serpin
superfamily and a leukocyte elastase and crosstalk between
neurons and T cells in the modulation of neuropathic pain.},
keywords = {Acute-Phase Proteins (NLM Chemicals) / Enzyme Inhibitors
(NLM Chemicals) / Serpina3n protein, mouse (NLM Chemicals) /
Serpina3n protein, rat (NLM Chemicals) / Serpins (NLM
Chemicals) / Leukocyte Elastase (NLM Chemicals)},
cin = {D050},
ddc = {610},
cid = {I:(DE-He78)D050-20160331},
pnm = {314 - Tumor immunology (POF3-314)},
pid = {G:(DE-HGF)POF3-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25915831},
pmc = {pmc:PMC4450999},
doi = {10.1038/nm.3852},
url = {https://inrepo02.dkfz.de/record/127706},
}