Molecular mechanisms of pruritus in prurigo nodularis

Front Immunol. 2023 Nov 23:14:1301817. doi: 10.3389/fimmu.2023.1301817. eCollection 2023.

Abstract

Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients' quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained "itch-scratch" vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune network; however, the underlying mechanism remains undetermined. Itch mediators play a key role in pruritus amplification in PN and understanding their action mechanism will undoubtedly lead to the development of novel targeted antipruritic agents. In this review, we describe a series of pruritogens and receptors involved in mediating itching in PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, and intracellular signaling pathways. Moreover, we provide a prospective outlook on potential therapies based on existing findings.

Keywords: pathogenetic mechanism; prurigo nodularis; pruritogen; pruritus; therapeutic target.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Humans
  • Neuropeptides*
  • Prurigo* / diagnosis
  • Prurigo* / drug therapy
  • Prurigo* / pathology
  • Pruritus / complications
  • Pruritus / etiology
  • Quality of Life

Substances

  • Neuropeptides

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Shanghai Association for Science and Technology (grant number 21Y11905100).