PMID- 30981714
OWN - NLM
STAT- MEDLINE
DCOM- 20200529
LR  - 20200529
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 80
DP  - 2019 Aug
TI  - CCL2/CCR2 signaling elicits itch- and pain-like behavior in a murine model of 
      allergic contact dermatitis.
PG  - 464-473
LID - S0889-1591(18)31210-8 [pii]
LID - 10.1016/j.bbi.2019.04.026 [doi]
AB  - Spontaneous itch and pain are the most common symptoms in various skin diseases, 
      including allergic contact dermatitis (ACD). The chemokine (C-C motif) ligand 2 
      (CCL2, also referred to as monocyte chemoattractant protein 1 (MCP-1)) and its 
      receptor CCR2 are involved in the pathophysiology of ACD, but little is known of 
      the role of CCL2/CCR2 for the itch- and pain-behaviors accompanying the murine 
      model of this disorder, termed contact hypersensitivity (CHS). C57BL/6 mice 
      previously sensitized to the hapten, squaric acid dibutyl ester, applied to the 
      abdomen were subsequently challenged twice with the hapten delivered to either 
      the cheek or to the hairy skin of the hind paw resulting in CHS at that site. By 
      24 h after the 2nd challenge to the hind paw CCL2 and CCR2 mRNA, protein, and 
      signaling activity were upregulated in the dorsal root ganglion (DRG). Calcium 
      imaging and whole-cell current-clamp recordings revealed that CCL2 directly acted 
      on its neuronal receptor, CCR2 to activate a subset of small-diameter, 
      nociceptive-like DRG neurons retrogradely labeled from the CHS site. Intradermal 
      injection of CCL2 into the site of CHS on the cheek evoked site-directed itch- 
      and pain-like behaviors which could be attenuated by prior delivery of an 
      antagonist of CCR2. In contrast, CCL2 failed to elicit either type of behavior in 
      control mice. Results are consistent with the hypothesis that CHS upregulates 
      CCL2/CCR2 signaling in a subpopulation of cutaneous small diameter DRG neurons 
      and that CCL2 can activate these neurons through neuronal CCR2 to elicit itch- 
      and pain-behavior. Targeting the CCL2/CCR2 signaling might be beneficial for the 
      treatment of the itch and pain sensations accompanying ACD in humans.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Jiang, Haowu
AU  - Jiang H
AD  - Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 
      06510, USA; Department of Anatomy, Histology and Embryology, Institute of Basic 
      Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, 
      School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
FAU - Cui, Huan
AU  - Cui H
AD  - Department of Anatomy, Histology and Embryology, Institute of Basic Medical 
      Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of 
      Basic Medicine, Peking Union Medical College, Beijing 100005, China.
FAU - Wang, Tao
AU  - Wang T
AD  - Department of Anatomy, Histology and Embryology, Institute of Basic Medical 
      Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of 
      Basic Medicine, Peking Union Medical College, Beijing 100005, China.
FAU - Shimada, Steven G
AU  - Shimada SG
AD  - Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 
      06510, USA.
FAU - Sun, Rui
AU  - Sun R
AD  - Department of Internal Medicine, Section of Digestive Diseases, Yale University, 
      New Haven, CT 06510, USA.
FAU - Tan, Zhiyong
AU  - Tan Z
AD  - Department of Pharmacology and Toxicology and Stark Neurosciences Research 
      Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
FAU - Ma, Chao
AU  - Ma C
AD  - Department of Anatomy, Histology and Embryology, Institute of Basic Medical 
      Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of 
      Basic Medicine, Peking Union Medical College, Beijing 100005, China. Electronic 
      address: machao@ibms.cams.cn.
FAU - LaMotte, Robert H
AU  - LaMotte RH
AD  - Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 
      06510, USA. Electronic address: robert.lamotte@yale.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190411
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cyclobutanes)
RN  - 0 (Receptors, CCR2)
RN  - 4RTO57VG65 (squaric acid dibutyl ester)
SB  - IM
CIN - Brain Behav Immun. 2019 Oct;81:12-13. PMID: 31271874
MH  - Animals
MH  - Chemokine CCL2/*metabolism/physiology
MH  - Cyclobutanes/pharmacology
MH  - Dermatitis, Allergic Contact/*metabolism/physiopathology
MH  - Disease Models, Animal
MH  - Ganglia, Spinal/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pain/metabolism
MH  - Patch-Clamp Techniques
MH  - Pruritus/metabolism
MH  - Receptors, CCR2/*metabolism/physiology
MH  - Sensory Receptor Cells/metabolism
MH  - Signal Transduction
MH  - Skin/metabolism
OTO - NOTNLM
OT  - Allergic contact dermatitis
OT  - Chemokine
OT  - Dorsal root ganglion
OT  - Itch
OT  - Pain
EDAT- 2019/04/15 06:00
MHDA- 2020/05/30 06:00
CRDT- 2019/04/15 06:00
PHST- 2018/12/14 00:00 [received]
PHST- 2019/03/14 00:00 [revised]
PHST- 2019/04/10 00:00 [accepted]
PHST- 2019/04/15 06:00 [pubmed]
PHST- 2020/05/30 06:00 [medline]
PHST- 2019/04/15 06:00 [entrez]
AID - S0889-1591(18)31210-8 [pii]
AID - 10.1016/j.bbi.2019.04.026 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2019 Aug;80:464-473. doi: 10.1016/j.bbi.2019.04.026. Epub 2019 
      Apr 11.