%0 Journal Article
%A Kälin, Stefanie
%A Miller, Kelly R
%A Kälin, Roland E
%A Jendrach, Marina
%A Witzel, Christian
%A Heppner, Frank L
%T CNS myeloid cells critically regulate heat hyperalgesia.
%J The journal of clinical investigation
%V 128
%N 7
%@ 0021-9738
%C Ann Arbor, Mich.
%I ASCJ
%M DZNE-2020-06367
%P 2774-2786
%D 2018
%X 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.
%K Animals
%K Calcitonin Gene-Related Peptide: physiology
%K Central Nervous System: pathology
%K Central Nervous System: physiopathology
%K Hot Temperature
%K Hyperalgesia: pathology
%K Hyperalgesia: physiopathology
%K Male
%K Mice
%K Mice, Inbred C57BL
%K Mice, Transgenic
%K Microglia: cytology
%K Microglia: physiology
%K Myeloid Cells: pathology
%K Myeloid Cells: physiology
%K Neuralgia: pathology
%K Neuralgia: physiopathology
%K Peptide Fragments: physiology
%K Peripheral Nerve Injuries: pathology
%K Peripheral Nerve Injuries: physiopathology
%K Peripheral Nerves: pathology
%K Peripheral Nerves: physiopathology
%K Spinal Cord Dorsal Horn: pathology
%K Spinal Cord Dorsal Horn: physiopathology
%K Peptide Fragments (NLM Chemicals)
%K calcitonin gene related peptide (1-7) (NLM Chemicals)
%K Calcitonin Gene-Related Peptide (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:29634489
%2 pmc:PMC6025970
%R 10.1172/JCI95305
%U https://pub.dzne.de/record/140045