Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation

Int J Mol Sci. 2021 Nov 16;22(22):12365. doi: 10.3390/ijms222212365.

Abstract

Although histamine is a well-known itch mediator, histamine H1-receptor blockers often lack efficacy in chronic itch. Recent molecular and cellular based studies have shown that non-histaminergic mediators, such as proteases, neuropeptides and cytokines, along with their cognate receptors, are involved in evocation and modulation of itch sensation. Many of these molecules are produced and secreted by immune cells, which act on sensory nerve fibers distributed in the skin to cause itching and sensitization. This understanding of the connections between immune cell-derived mediators and sensory nerve fibers has led to the development of new treatments for itch. This review summarizes current knowledge of immune cell-derived itch mediators and neuronal response mechanisms, and discusses therapeutic agents that target these systems.

Keywords: cytokines; immune cell; itch mediator and modulator; sensory neuron.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • Cytokines / metabolism
  • Gene Expression
  • Histamine / immunology*
  • Histamine / metabolism
  • Histamine Antagonists / therapeutic use
  • Humans
  • Immunologic Factors / therapeutic use*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / pathology
  • Myeloid Cells / drug effects
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • Neuropeptides / antagonists & inhibitors
  • Neuropeptides / immunology
  • Neuropeptides / metabolism
  • Peptide Hydrolases / immunology
  • Peptide Hydrolases / metabolism
  • Protease Inhibitors / therapeutic use
  • Pruritus / drug therapy
  • Pruritus / genetics
  • Pruritus / immunology*
  • Pruritus / pathology
  • Receptors, Histamine H1 / genetics
  • Receptors, Histamine H1 / immunology*
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / immunology*
  • Sensory Receptor Cells / pathology
  • Skin / drug effects
  • Skin / immunology
  • Skin / innervation
  • Skin / pathology

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Cytokines
  • Histamine Antagonists
  • Immunologic Factors
  • Neuropeptides
  • Protease Inhibitors
  • Receptors, Histamine H1
  • Histamine
  • Peptide Hydrolases