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

Journal of Clinical Investigation

Volumn 122, Issue 6, 2012, Pages 2195-2207

  Liu, Tong ^a,d   Berta, Temugin ^a,d   Xu, Zhen Zhong ^a,d   Park, Chul Kyu ^a,d   Zhang, Ling ^a   Lü, Ning ^a   Liu, Qin ^b   Liu, Yang ^c   Gao, Yong Jing ^a   Liu, Yen Chin ^a   Ma, Qiufu ^c   Dong, Xinzhong ^b   Ji, Ru Rong ^a,d  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GASTRIN; HISTAMINE; PEPTIDE; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 7; VANILLOID RECEPTOR 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CENTRAL NERVOUS SYSTEM SENSITIZATION; CONTROLLED STUDY; DRY SKIN; EXCITATORY POSTSYNAPTIC POTENTIAL; FEMALE; GENE EXPRESSION; GENE SILENCING; LONG TERM POTENTIATION; MALE; MOUSE; NERVE POTENTIAL; NOCICEPTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PRURITUS; SENSORY NERVE CELL; SIGNAL TRANSDUCTION; SPINAL CORD; SPINAL GANGLION; SYNAPTIC TRANSMISSION; WILD TYPE;

ACTION POTENTIALS; ANIMALS; GANGLIA, SPINAL; GASTRIN-RELEASING PEPTIDE; GENE EXPRESSION REGULATION; GENE KNOCKDOWN TECHNIQUES; MEMBRANE GLYCOPROTEINS; MICE; MICE, KNOCKOUT; PAIN; PRURITUS; SENSORY RECEPTOR CELLS; SPINAL CORD; SYNAPTIC TRANSMISSION; TOLL-LIKE RECEPTOR 3; TOLL-LIKE RECEPTOR 7; TRPV CATION CHANNELS;

EID: 84861794417     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI45414     Document Type: Article

References (49)

1. Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006;7(7):535-547. (Pubitemid 43995431)
2. Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet. 2003;361(9358):690- 694. (Pubitemid 36253608)
3. Paus R, Schmelz M, Biro T, Steinhoff M. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest. 2006;116(5):1174-1186.
4. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373-384.
5. Town T, Jeng D, Alexopoulou L, Tan J, Flavell RA. Microglia recognize double-stranded RNA via TLR3. J Immunol. 2006;176(6):3804-3812. (Pubitemid 43364029)
6. Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med. 2004;10(12):1366-1373. (Pubitemid 40022719)
7. Kim D, et al. A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J Biol Chem. 2007;282(20):14975-14983. (Pubitemid 47093373)
8. Obata K, et al. Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury. J Neurochem. 2008;105(6):2249-2259. (Pubitemid 351782279)
9. Tanga FY, Nutile-McMenemy N, Deleo JA. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci U S A. 2005;102(16):5856-5861. (Pubitemid 40559649)
10. Wadachi R, Hargreaves KM. Trigeminal nociceptors express TLR-4 and CD14: a mechanism for pain due to infection. J Dent Res. 2006;85(1):49-53. (Pubitemid 43827762)
11. Diogenes A, Ferraz CC, Akopian AN, Henry MA, Hargreaves KM. LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons. J Dent Res. 2011;90(6):759-764.
12. Cameron JS, et al. Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals. J Neurosci. 2007;27(47):13033-13041. (Pubitemid 350159595)
13. Liu T, Xu ZZ, Park CK, Berta T, Ji RR. Toll-like receptor 7 mediates pruritus. Nat Neurosci. 2010;13(12):1460-1462.
14. Ji RR, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696-705. (Pubitemid 37415022)
15. Patel KN, Dong X. An itch to be scratched. Neuron. 2010;68(3):334-339.
16. Ruscheweyh R, Wilder-Smith O, Drdla R, Liu XG, Sandkuhler J. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy. Mol Pain. 2011;7:20.
17. Ji RR, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696-705. (Pubitemid 37415022)
18. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001;413(6857):732-738. (Pubitemid 33009951)
19. Liu Q, et al. Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell. 2009;139(7):1353-1365.
20. Akiyama T, Merrill AW, Carstens MI, Carstens E. Activation of superficial dorsal horn neurons in the mouse by a PAR-2 agonist and 5-HT: potential role in itch. J Neurosci. 2009;29(20):6691-6699.
21. Steinhoff M, et al. Proteinase-activated receptor- 2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci. 2003;23(15):6176-6180. (Pubitemid 36875617)
22. Liu Q, et al. The distinct roles of two GPCRs, MrgprC11 and PAR2, in itch and hyperalgesia. Sci Signal. 2011;4(181):ra45.
23. Ross SE, et al. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron. 2010;65(6):886-898.
24. Kim SJ, et al. Analysis of cellular and behavioral responses to imiquimod reveals a unique itch pathway in transient receptor potential vanilloid 1 (TRPV1)-expressing neurons. Proc Natl Acad Sci U S A. 2011;108(8):3371-3376.
25. Shimada SG, LaMotte RH. Behavioral differentiation between itch and pain in mouse. Pain. 2008;139(3):681-687.
26. Akiyama T, Carstens MI, Carstens E. Facial injections of pruritogens and algogens excite partly overlapping populations of primary and secondorder trigeminal neurons in mice. J Neurophysiol. 2010;104(5):2442-2450.
27. Cameron JS, et al. Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals. J Neurosci. 2007;27(47):13033-13041. (Pubitemid 350159595)
28. Sun YG, Chen ZF. A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature. 2007;448(7154):700-703.
29. Imamachi N, et al. TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proc Natl Acad Sci U S A. 2009;106(27):11330-11335.
30. Kawasaki Y, Zhang L, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin- 6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci. 2008;28(20):5189-5194.
31. Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF. Cellular basis of itch sensation. Science. 2009;325(5947):1531-1534.
32. Toshchakov VU, Basu S, Fenton MJ, Vogel SN. Differential involvement of BB loops of toll-IL-1 resistance (TIR) domain-containing adapter proteins in. J Immunol. 2005;175(1):494-500. (Pubitemid 40884354)
33. Steinhoff M, Cevikbas F, Ikoma A, Berger TG. Pruritus: management algorithms and experimental therapies. Semin Cutan Med Surg. 2011;30(2):127-137.
34. Miyamoto T, Nojima H, Shinkado T, Nakahashi T, Kuraishi Y. Itch-associated response induced by experimental dry skin in mice. Jpn J Pharmacol. 2002;88(3):285-292. (Pubitemid 34302979)
35. Akiyama T, Carstens MI, Carstens E. Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch. Pain. 2010;151(2):378-383.
36. Yosipovitch G, Carstens E, McGlone F. Chronic itch and chronic pain: Analogous mechanisms. Pain. 2007;131(1-2):4-7. (Pubitemid 47187897)
37. Shim WS, Oh U. Histamine-induced itch and its relationship with pain. Mol Pain. 2008;4:29.
38. Han SK, Mancino V, Simon MI. Phospholipase Cbeta 3 mediates the scratching response activated by the histamine H1 receptor on C-fiber nociceptive neurons. Neuron. 2006;52(4):691-703. (Pubitemid 44781169)
39. Wilson SR, et al. TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor- mediated itch. Nat Neurosci. 2011;14(5):595-602.
40. Mishra SK, Tisel SM, Orestes P, Bhangoo SK, Hoon MA. TRPV1-lineage neurons are required for thermal sensation. EMBO J. 2011;30(3):582-593.
41. Liu Y, et al. VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron. 2010;68(3):543-556.
42. Carstens EE, Carstens MI, Simons CT, Jinks SL. Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport. 2010; 21(4):303-308.
43. Okun E, et al. Toll-like receptor 3 inhibits memory retention and constrains adult hippocampal neurogenesis. Proc Natl Acad Sci U S A. 2010;107(35):15625-15630.
44. Bsibsi M, et al. The microtubule regulator stathmin is an endogenous protein agonist for TLR3. J Immunol. 2010;184(12):6929-6937.
45. Ma Q. Labeled lines meet and talk: population coding of somatic sensations. J Clin Invest. 2010;120(11):3773-3778.
46. Kulka M, Alexopoulou L, Flavell RA, Metcalfe DD. Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol. 2004;114(1):174-182.
47. Tohyama M, et al. dsRNA-mediated innate immunity of epidermal keratinocytes. Biochem Biophys Res Commun. 2005;335(2):505-511. (Pubitemid 41140251)
48. Botchkarev VA, et al. Neurotrophins in skin biology and pathology. J Invest Dermatol. 2006; 126(8):1719-1727. (Pubitemid 44086504)
49. Park CK, Lu N, Xu ZZ, Liu T, Serhan CN, Ji RR. Resolving TRPV1- and TNF-alpha-mediated spinal cord synaptic plasticity and inflammatory pain with neuroprotectin D1. J Neurosci. 2011;31(42):15072-15085.