Skip to main content

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

Publication ,  Journal Article
Liu, T; Berta, T; Xu, Z-Z; Park, C-K; Zhang, L; Lü, N; Liu, Q; Liu, Y; Gao, Y-J; Liu, Y-C; Ma, Q; Dong, X; Ji, R-R
Published in: J Clin Invest
June 2012

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 demonstrate a critical role of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic transmission, and central sensitization. TLR3 may serve as a new target for developing anti-itch treatment.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

June 2012

Volume

122

Issue

6

Start / End Page

2195 / 2207

Location

United States

Related Subject Headings

  • Toll-Like Receptor 7
  • Toll-Like Receptor 3
  • TRPV Cation Channels
  • Synaptic Transmission
  • Spinal Cord
  • Sensory Receptor Cells
  • Pruritus
  • Pain
  • Mice, Knockout
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, T., Berta, T., Xu, Z.-Z., Park, C.-K., Zhang, L., Lü, N., … Ji, R.-R. (2012). TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest, 122(6), 2195–2207. https://doi.org/10.1172/JCI45414
Liu, Tong, Temugin Berta, Zhen-Zhong Xu, Chul-Kyu Park, Ling Zhang, Ning Lü, Qin Liu, et al. “TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice.J Clin Invest 122, no. 6 (June 2012): 2195–2207. https://doi.org/10.1172/JCI45414.
Liu T, Berta T, Xu Z-Z, Park C-K, Zhang L, Lü N, et al. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest. 2012 Jun;122(6):2195–207.
Liu, Tong, et al. “TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice.J Clin Invest, vol. 122, no. 6, June 2012, pp. 2195–207. Pubmed, doi:10.1172/JCI45414.
Liu T, Berta T, Xu Z-Z, Park C-K, Zhang L, Lü N, Liu Q, Liu Y, Gao Y-J, Liu Y-C, Ma Q, Dong X, Ji R-R. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest. 2012 Jun;122(6):2195–2207.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

June 2012

Volume

122

Issue

6

Start / End Page

2195 / 2207

Location

United States

Related Subject Headings

  • Toll-Like Receptor 7
  • Toll-Like Receptor 3
  • TRPV Cation Channels
  • Synaptic Transmission
  • Spinal Cord
  • Sensory Receptor Cells
  • Pruritus
  • Pain
  • Mice, Knockout
  • Mice