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@ARTICLE{Klin:140045,
author = {Kälin, Stefanie and Miller, Kelly R and Kälin, Roland E
and Jendrach, Marina and Witzel, Christian and Heppner,
Frank L},
title = {{CNS} myeloid cells critically regulate heat hyperalgesia.},
journal = {The journal of clinical investigation},
volume = {128},
number = {7},
issn = {0021-9738},
address = {Ann Arbor, Mich.},
publisher = {ASCJ},
reportid = {DZNE-2020-06367},
pages = {2774-2786},
year = {2018},
abstract = {Activation of non-neuronal microglia is thought to play a
causal role in spinal processing of neuropathic pain. To
specifically investigate microglia-mediated effects in a
model of neuropathic pain and overcome the methodological
limitations of previous approaches exploring microglia
function upon nerve injury, we selectively ablated resident
microglia by intracerebroventricular ganciclovir infusion
into male CD11b-HSVTK-transgenic mice, which was followed by
a rapid, complete, and persistent (23 weeks) repopulation of
the CNS by peripheral myeloid cells. In repopulated mice
that underwent sciatic nerve injury, we observed a normal
response to mechanical stimuli, but an absence of thermal
hypersensitivity ipsilateral to the injured nerve.
Furthermore, we found that neuronal expression of calcitonin
gene-related peptide (CGRP), which is a marker of neurons
essential for heat responses, was diminished in the dorsal
horn of the spinal cord in repopulated mice. These findings
identify distinct mechanisms for heat and mechanical
hypersensitivity and highlight a crucial contribution of CNS
myeloid cells in the facilitation of noxious heat.},
keywords = {Animals / Calcitonin Gene-Related Peptide: physiology /
Central Nervous System: pathology / Central Nervous System:
physiopathology / Hot Temperature / Hyperalgesia: pathology
/ Hyperalgesia: physiopathology / Male / Mice / Mice, Inbred
C57BL / Mice, Transgenic / Microglia: cytology / Microglia:
physiology / Myeloid Cells: pathology / Myeloid Cells:
physiology / Neuralgia: pathology / Neuralgia:
physiopathology / Peptide Fragments: physiology / Peripheral
Nerve Injuries: pathology / Peripheral Nerve Injuries:
physiopathology / Peripheral Nerves: pathology / Peripheral
Nerves: physiopathology / Spinal Cord Dorsal Horn: pathology
/ Spinal Cord Dorsal Horn: physiopathology / Peptide
Fragments (NLM Chemicals) / calcitonin gene related peptide
(1-7) (NLM Chemicals) / Calcitonin Gene-Related Peptide (NLM
Chemicals)},
cin = {AG Heppner},
ddc = {610},
cid = {I:(DE-2719)1810007},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29634489},
pmc = {pmc:PMC6025970},
doi = {10.1172/JCI95305},
url = {https://pub.dzne.de/record/140045},
}