Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice

Neuron. 2010 Mar 25;65(6):886-98. doi: 10.1016/j.neuron.2010.02.025.


Itch is the least well understood of all the somatic senses, and the neural circuits that underlie this sensation are poorly defined. Here we show that the atonal-related transcription factor Bhlhb5 is transiently expressed in the dorsal horn of the developing spinal cord and appears to play a role in the formation and regulation of pruritic (itch) circuits. Mice lacking Bhlhb5 develop self-inflicted skin lesions and show significantly enhanced scratching responses to pruritic agents. Through genetic fate-mapping and conditional ablation, we provide evidence that the pruritic phenotype in Bhlhb5 mutants is due to selective loss of a subset of inhibitory interneurons in the dorsal horn. Our findings suggest that Bhlhb5 is required for the survival of a specific population of inhibitory interneurons that regulate pruritus, and provide evidence that the loss of inhibitory synaptic input results in abnormal itch.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / deficiency*
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Cell Survival / physiology
  • Gene Knock-In Techniques / methods
  • Interneurons / metabolism
  • Interneurons / pathology*
  • Mice
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Neural Inhibition / physiology
  • Posterior Horn Cells / metabolism
  • Posterior Horn Cells / pathology*
  • Pruritus / genetics*
  • Pruritus / pathology*
  • Pruritus / physiopathology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology


  • Basic Helix-Loop-Helix Transcription Factors
  • Bhlhe22 protein, mouse