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Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma.

Publication ,  Journal Article
Chen, O; He, Q; Han, Q; Furutani, K; Gu, Y; Olexa, M; Ji, R-R
Published in: The Journal of clinical investigation
February 2023

Our understanding of neuropathic itch is limited due to a lack of relevant animal models. Patients with cutaneous T cell lymphoma (CTCL) experience severe itching. Here, we characterize a mouse model of chronic itch with remarkable lymphoma growth, immune cell accumulation, and persistent pruritus. Intradermal CTCL inoculation produced time-dependent changes in nerve innervations in lymphoma-bearing skin. In the early phase (20 days), CTCL caused hyperinnervations in the epidermis. However, chronic itch was associated with loss of epidermal nerve fibers in the late phases (40 and 60 days). CTCL was also characterized by marked nerve innervations in mouse lymphoma. Blockade of C-fibers reduced pruritus at early and late phases, whereas blockade of A-fibers only suppressed late-phase itch. Intrathecal (i.t.) gabapentin injection reduced late-phase, but not early-phase, pruritus. IL-31 was upregulated in mouse lymphoma, whereas its receptor Il31ra was persistently upregulated in Trpv1-expressing sensory neurons in mice with CTCL. Intratumoral anti-IL-31 treatment effectively suppressed CTCL-induced scratching and alloknesis (mechanical itch). Finally, i.t. administration of a TLR4 antagonist attenuated pruritus in early and late phases and in both sexes. Collectively, we have established a mouse model of neuropathic and cancer itch with relevance to human disease. Our findings also suggest distinct mechanisms underlying acute, chronic, and neuropathic itch.

Duke Scholars

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Published In

The Journal of clinical investigation

DOI

EISSN

1558-8238

ISSN

0021-9738

Publication Date

February 2023

Volume

133

Issue

4

Start / End Page

e160807

Related Subject Headings

  • Skin
  • Sensory Receptor Cells
  • Pruritus
  • Mice
  • Male
  • Lymphoma
  • Immunology
  • Female
  • Disease Models, Animal
  • Animals
 

Citation

APA
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ICMJE
MLA
NLM
Chen, O., He, Q., Han, Q., Furutani, K., Gu, Y., Olexa, M., & Ji, R.-R. (2023). Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma. The Journal of Clinical Investigation, 133(4), e160807. https://doi.org/10.1172/jci160807
Chen, Ouyang, Qianru He, Qingjian Han, Kenta Furutani, Yun Gu, Madelynne Olexa, and Ru-Rong Ji. “Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma.The Journal of Clinical Investigation 133, no. 4 (February 2023): e160807. https://doi.org/10.1172/jci160807.
Chen O, He Q, Han Q, Furutani K, Gu Y, Olexa M, et al. Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma. The Journal of clinical investigation. 2023 Feb;133(4):e160807.
Chen, Ouyang, et al. “Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma.The Journal of Clinical Investigation, vol. 133, no. 4, Feb. 2023, p. e160807. Epmc, doi:10.1172/jci160807.
Chen O, He Q, Han Q, Furutani K, Gu Y, Olexa M, Ji R-R. Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma. The Journal of clinical investigation. 2023 Feb;133(4):e160807.

Published In

The Journal of clinical investigation

DOI

EISSN

1558-8238

ISSN

0021-9738

Publication Date

February 2023

Volume

133

Issue

4

Start / End Page

e160807

Related Subject Headings

  • Skin
  • Sensory Receptor Cells
  • Pruritus
  • Mice
  • Male
  • Lymphoma
  • Immunology
  • Female
  • Disease Models, Animal
  • Animals