TY  - JOUR
AU  - Kälin, Stefanie
AU  - Miller, Kelly R
AU  - Kälin, Roland E
AU  - Jendrach, Marina
AU  - Witzel, Christian
AU  - Heppner, Frank L
TI  - CNS myeloid cells critically regulate heat hyperalgesia.
JO  - The journal of clinical investigation
VL  - 128
IS  - 7
SN  - 0021-9738
CY  - Ann Arbor, Mich.
PB  - ASCJ
M1  - DZNE-2020-06367
SP  - 2774-2786
PY  - 2018
AB  - 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.
KW  - Animals
KW  - Calcitonin Gene-Related Peptide: physiology
KW  - Central Nervous System: pathology
KW  - Central Nervous System: physiopathology
KW  - Hot Temperature
KW  - Hyperalgesia: pathology
KW  - Hyperalgesia: physiopathology
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Microglia: cytology
KW  - Microglia: physiology
KW  - Myeloid Cells: pathology
KW  - Myeloid Cells: physiology
KW  - Neuralgia: pathology
KW  - Neuralgia: physiopathology
KW  - Peptide Fragments: physiology
KW  - Peripheral Nerve Injuries: pathology
KW  - Peripheral Nerve Injuries: physiopathology
KW  - Peripheral Nerves: pathology
KW  - Peripheral Nerves: physiopathology
KW  - Spinal Cord Dorsal Horn: pathology
KW  - Spinal Cord Dorsal Horn: physiopathology
KW  - Peptide Fragments (NLM Chemicals)
KW  - calcitonin gene related peptide (1-7) (NLM Chemicals)
KW  - Calcitonin Gene-Related Peptide (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29634489
C2  - pmc:PMC6025970
DO  - DOI:10.1172/JCI95305
UR  - https://pub.dzne.de/record/140045
ER  -