PMID- 31954829
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 429
DP  - 2020 Mar 1
TI  - Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch.
PG  - 245-255
LID - S0306-4522(20)30023-3 [pii]
LID - 10.1016/j.neuroscience.2020.01.010 [doi]
AB  - Toll-like receptors (TLRs) have been implicated in pain and itch regulation. 
      TLR2, a TLR family member that detects microbial membrane components, has been 
      implicated in pathologic pain. However, the role of TLR2 in pruritic and 
      nociceptive responses has not been thoroughly investigated. In this study, we 
      found that TLR2 was expressed in mouse dorsal root ganglia (DRG) and trigeminal 
      ganglia (TG) neurons. Itch and pain behaviors, including histamine-dependent and 
      histamine-independent acute itching, acetone/diethyl ether/water and 
      2,4-dinitrofluorobenzene-induced chronic itching and inflammatory pain, were 
      largely attenuated in TLR2 knockout (KO) mice. The TLR2 agonist Pam3CSK4, which 
      targets TLR2/1 heterodimers, evoked pain and itch behavior, whereas lipoteichoic 
      acid (LTA) and zymosan, which recognize TLR2/6 heterodimers, produced only pain 
      response. The TLR2 agonist-induced nociceptive and pruritic behaviors were 
      largely diminished in transient receptor potential vanilloid 1 (TRPV1) and 
      transient receptor potential ankyrin 1 (TRPA1) KO mice. Finally, Pam3Csk4 and 
      zymosan increased the [Ca2(+)](i) in DRG neurons from wild-type mice. However, 
      the enhancement of [Ca2(+)](i) was largely inhibited in the DRG neurons from 
      TRPV1 and TRPA1 KO mice. Our results demonstrate that TLR2 is involved in 
      different itch and pain behaviors through activating TLR1/TLR2 or TLR6/TLR2 
      heterodimers via TRPV1 and TRPA1 channels.
CI  - Copyright (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Wang, Ting-Ting
AU  - Wang TT
AD  - The First Rehabilitation Hospital of Shanghai, Tongji University School of 
      Medicine, Shanghai 200090, China; Department of Dermatology, Tongren Hospital 
      Shanghai Jiao Tong University School of Medicine Shanghai 200336, China; State 
      Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Department of Translational Neuroscience, Institutes of Brain Science, 
      Fudan University, Shanghai 200032, China.
FAU - Xu, Xian-Yun
AU  - Xu XY
AD  - The First Rehabilitation Hospital of Shanghai, Tongji University School of 
      Medicine, Shanghai 200090, China; Key Laboratory of Spine and Spinal Cord Injury 
      Repair and Regeneration of Ministry of Education, Orthopaedic Department of 
      Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; 
      Department of Anatomy and Histology, Tongji University School of Medicine, 
      Shanghai 200092, China.
FAU - Lin, Wei
AU  - Lin W
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Department of Translational Neuroscience, Institutes of Brain Science, 
      Fudan University, Shanghai 200032, China.
FAU - Hu, Dan-Dan
AU  - Hu DD
AD  - The First Rehabilitation Hospital of Shanghai, Tongji University School of 
      Medicine, Shanghai 200090, China; Key Laboratory of Spine and Spinal Cord Injury 
      Repair and Regeneration of Ministry of Education, Orthopaedic Department of 
      Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; 
      Department of Anatomy and Histology, Tongji University School of Medicine, 
      Shanghai 200092, China.
FAU - Shi, Wu
AU  - Shi W
AD  - The First Rehabilitation Hospital of Shanghai, Tongji University School of 
      Medicine, Shanghai 200090, China; Key Laboratory of Spine and Spinal Cord Injury 
      Repair and Regeneration of Ministry of Education, Orthopaedic Department of 
      Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; 
      Department of Anatomy and Histology, Tongji University School of Medicine, 
      Shanghai 200092, China.
FAU - Jia, Xin
AU  - Jia X
AD  - The First Rehabilitation Hospital of Shanghai, Tongji University School of 
      Medicine, Shanghai 200090, China; Key Laboratory of Spine and Spinal Cord Injury 
      Repair and Regeneration of Ministry of Education, Orthopaedic Department of 
      Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China; 
      Department of Anatomy and Histology, Tongji University School of Medicine, 
      Shanghai 200092, China.
FAU - Wang, Hui
AU  - Wang H
AD  - The First Rehabilitation Hospital of Shanghai, Tongji University School of 
      Medicine, Shanghai 200090, China.
FAU - Song, Ning-Jing
AU  - Song NJ
AD  - Department of Dermatology, Tongren Hospital Shanghai Jiao Tong University School 
      of Medicine Shanghai 200336, China.
FAU - Zhang, Yu-Qiu
AU  - Zhang YQ
AD  - State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Department of Translational Neuroscience, Institutes of Brain Science, 
      Fudan University, Shanghai 200032, China.
FAU - Zhang, Ling
AU  - Zhang L
AD  - The First Rehabilitation Hospital of Shanghai, Tongji University School of 
      Medicine, Shanghai 200090, China; Department of Anatomy and Histology, Tongji 
      University School of Medicine, Shanghai 200092, China; Department of Dermatology, 
      Tongren Hospital Shanghai Jiao Tong University School of Medicine Shanghai 
      200336, China. Electronic address: lzhang0808@tongji.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200116
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Transient Receptor Potential Channels)
SB  - IM
MH  - Animals
MH  - Ganglia, Spinal
MH  - Mice
MH  - *Pain
MH  - *Pruritus/chemically induced
MH  - TRPA1 Cation Channel
MH  - TRPV Cation Channels/genetics
MH  - *Toll-Like Receptor 2/genetics
MH  - Transient Receptor Potential Channels
OTO - NOTNLM
OT  - TLR2
OT  - TRPA1
OT  - TRPV1
OT  - itch
OT  - pain
EDAT- 2020/01/20 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/01/20 06:00
PHST- 2019/08/08 00:00 [received]
PHST- 2020/01/03 00:00 [revised]
PHST- 2020/01/07 00:00 [accepted]
PHST- 2020/01/20 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/01/20 06:00 [entrez]
AID - S0306-4522(20)30023-3 [pii]
AID - 10.1016/j.neuroscience.2020.01.010 [doi]
PST - ppublish
SO  - Neuroscience. 2020 Mar 1;429:245-255. doi: 10.1016/j.neuroscience.2020.01.010. 
      Epub 2020 Jan 16.