Cross-sensitization of histamine-independent itch in mouse primary sensory neurons

Neuroscience. 2012 Dec 13:226:305-12. doi: 10.1016/j.neuroscience.2012.09.019. Epub 2012 Sep 19.


Overexpression of pruritogens and their precursors may contribute to the sensitization of histamine-dependent and -independent itch-signaling pathways in chronic itch. We presently investigated self- and cross-sensitization of scratching behavior elicited by various pruritogens, and their effects on primary sensory neurons. The MrgprC11 agonist BAM8-22 exhibited self- and reciprocal cross-sensitization of scratching evoked by the protease-activated receptor-2 (PAR-2) agonist SLIGRL. The MrgprA3 agonist chloroquine unidirectionally cross-sensitized BAM8-22-evoked scratching. Histamine unidirectionally cross-sensitized scratching evoked by chloroquine and BAM8-22. SLIGRL unidirectionally cross-sensitized scratching evoked by chloroquine. Dorsal root ganglion (DRG) cells responded to various combinations of pruritogens and algogens. Neither chloroquine, BAM8-22 nor histamine had any effect on responses of DRG cell responses to subsequently applied pruritogens, implying that their behavioral self- and cross-sensitization effects are mediated indirectly. SLIGRL unilaterally cross-sensitized responses of DRG cells to chloroquine and BAM8-22, consistent with the behavioral data. These results indicate that unidirectional cross-sensitization of histamine-independent itch-signaling pathways might occur at a peripheral site through PAR-2. PAR-2 expressed in pruriceptive nerve endings is a potential target to reduce sensitization associated with chronic itch.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Calcium Signaling / physiology
  • Chloroquine
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / physiology
  • Histamine / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroimaging
  • Peptide Fragments
  • Pruritus / chemically induced
  • Pruritus / physiopathology*
  • Pruritus / psychology
  • Receptor, PAR-2 / agonists
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology*
  • Signal Transduction / physiology


  • Peptide Fragments
  • Receptor, PAR-2
  • bovine adrenal medulla 8-22
  • Histamine
  • Chloroquine