TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice.

The Journal of Clinical Investigation
Tong LiuRu-Rong Ji

Abstract

Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs) that coexpress the itch signaling pathway components transient receptor potential subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a TLR3 agonist induces inward currents and action potentials in DRG neurons and elicited scratching in WT mice but not Tlr3(-/-) mice. Furthermore, excitatory synaptic transmission in spinal cord slices and long-term potentiation in the intact spinal cord were impaired in Tlr3(-/-) mice but not Tlr7(-/-) mice. Consequently, central sensitization-driven pain hypersensitivity, but not acute pain, was impaired in Tlr3(-/-) mice. In addition, TLR3 knockdown in DRGs also attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was substantially reduced in Tlr3(-/-) mice. Our findings...Continue Reading

References

Apr 13, 2002·Japanese Journal of Pharmacology·Takayuki MiyamotoYasushi Kuraishi
Feb 28, 2003·Lancet·Gil YosipovitchMartin Schmelz
Nov 20, 2003·Trends in Neurosciences·Ru-Rong JiClifford J Woolf
Jul 9, 2004·The Journal of Allergy and Clinical Immunology·Marianna KulkaDean D Metcalfe
Apr 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Flobert Y TangaJoyce A DeLeo
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vladimir U ToshchakovStefanie N Vogel
Aug 10, 2005·Biochemical and Biophysical Research Communications·Mikiko TohyamaKoji Hashimoto
Dec 24, 2005·Journal of Dental Research·R Wadachi, K M Hargreaves
Mar 7, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Terrence TownRichard A Flavell
May 4, 2006·The Journal of Clinical Investigation·Ralf PausMartin Steinhoff
Jun 23, 2006·Nature Reviews. Neuroscience·Akihiko IkomaMartin Schmelz
Jul 18, 2006·The Journal of Investigative Dermatology·Vladimir A BotchkarevCarlo Pincelli
May 26, 2007·Pain·Gil YosipovitchFrancis McGlone
Nov 23, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jill S CameronTimothy Vartanian
Mar 28, 2008·Journal of Neurochemistry·Koichi ObataKoichi Noguchi
Aug 1, 2008·Molecular Pain·Won-Sik Shim, Uhtaek Oh
Sep 16, 2008·Pain·Steven G Shimada, Robert H LaMotte
May 22, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tasuku AkiyamaE Carstens
Jul 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Noritaka ImamachiSang-Kyou Han
Aug 8, 2009·Science·Yan-Gang SunZhou-Feng Chen
Feb 4, 2010·Neuroreport·Earl E CarstensSteven L Jinks
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Malika BsibsiJohannes M van Noort
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eitan OkunMark P Mattson
Nov 3, 2010·Nature Neuroscience·Tong LiuRu-Rong Ji
Nov 3, 2010·Neuron·Kush N Patel, Xinzhong Dong
Nov 3, 2010·The Journal of Clinical Investigation·Qiufu Ma
Dec 9, 2010·The EMBO Journal·Santosh K MishraMark A Hoon
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Se-Jeong KimSang-Kyou Han
Mar 12, 2011·Journal of Dental Research·A DiogenesK M Hargreaves
Mar 30, 2011·Molecular Pain·Ruth RuscheweyhJürgen Sandkühler
Jul 20, 2011·Seminars in Cutaneous Medicine and Surgery·Martin SteinhoffTimothy G Berger
Jul 22, 2011·Science Signaling·Qin LiuXinzhong Dong
Oct 22, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chul-Kyu ParkRu-Rong Ji

❮ Previous
Next ❯

Citations

May 3, 2013·Pflügers Archiv : European journal of physiology·Tong Liu, Ru-Rong Ji
Dec 29, 2012·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yongtang SongHongbing Xiang
Apr 3, 2013·Annales de dermatologie et de vénéréologie·A Petit
Mar 26, 2013·The Journal of Clinical Investigation·Farzad AlemiCarlos U Corvera
Aug 2, 2013·Biological & Pharmaceutical Bulletin·Yasushi Kuraishi
Aug 16, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Promila PagadalaRu-Rong Ji
Jun 25, 2013·Brain : a Journal of Neurology·Amar Dhand, Michael J Aminoff
Jan 30, 2014·Nature Neuroscience·Diana M BautistaMark A Hoon
May 14, 2014·Annual Review of Biophysics·Liang Han, Xinzhong Dong
Jul 16, 2014·Experimental Neurology·Kristina A KigerlRobert W Keane
Jul 27, 2014·Brain, Behavior, and Immunity·Adee HeimanStella Elkabes
Jul 3, 2013·Expert Opinion on Investigational Drugs·Heike BeneckeSonja Ständer
Aug 21, 2014·Molecular Brain·Hyunjung MinSung Joong Lee
Jan 21, 2014·The Journal of Investigative Dermatology·Momoko NakaoShinichi Sato
Sep 20, 2015·Seminars in Immunopathology·Shuohao Sun, Xinzhong Dong
Jul 31, 2013·Neuroscience·Tasuku Akiyama, E Carstens
Apr 22, 2015·Cellular and Molecular Life Sciences : CMLS·Jialie LuoHongzhen Hu
May 2, 2015·Clinical Reviews in Allergy & Immunology·Nicholas K MollanazarGil Yosipovitch
Jan 10, 2017·Journal of Molecular Biology·Nicole J Yang, Isaac M Chiu
Jun 10, 2016·Cell Host & Microbe·Pankaj BaralIsaac M Chiu
Feb 2, 2017·Neuroscience Bulletin·Isaac M Chiu
Sep 19, 2017·Anesthesia and Analgesia·Jan Rossaint, Alexander Zarbock
Feb 21, 2018·Anesthesiology·Ru-Rong JiWilliam Maixner
Sep 12, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xenia KodjiSusan D Brain
Aug 1, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sunita KeshariChun-Ming Huang
Mar 17, 2016·Anesthesiology·Benjamin E SteinbergPeder S Olofsson
May 18, 2016·Pain·Isaac M ChiuClifford J Woolf

❮ Previous
Next ❯

Methods Mentioned

BETA
antisense oligodeoxynucleotides
PCR
Protein Assay

Related Concepts

Related Feeds

Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. Discover the latest research on atopic dermatitis here.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.