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

T. Akiyama, M. Tominaga, A. Davoodi, M. Nagamine, K. Blansit, A. Horwitz, M. I. Carstens, E. Carstens

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)305-312
Number of pages8
StatePublished - Dec 13 2012
Externally publishedYes


  • Calcium imaging
  • Cross-sensitization
  • Dorsal root ganglion (DRG) cell
  • Itch
  • Pruritogen
  • Scratching

ASJC Scopus subject areas

  • Neuroscience(all)


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