Spinal Neuropeptide Y1 Receptor-Expressing Neurons Form an Essential Excitatory Pathway for Mechanical Itch

Cell Rep. 2019 Jul 16;28(3):625-639.e6. doi: 10.1016/j.celrep.2019.06.033.


Acute itch can be generated by either chemical or mechanical stimuli, which activate separate pathways in the periphery and spinal cord. While substantial progress has been made in mapping the transmission pathway for chemical itch, the central pathway for mechanical itch remains obscure. Using complementary genetic and pharmacological manipulations, we show that excitatory neurons marked by the expression of the neuropeptide Y1 receptor (Y1Cre neurons) form an essential pathway in the dorsal spinal cord for the transmission of mechanical but not chemical itch. Ablating or silencing the Y1Cre neurons abrogates mechanical itch, while chemogenetic activation induces scratching. Moreover, using Y1 conditional knockout mice, we demonstrate that endogenous neuropeptide Y (NPY) acts via dorsal-horn Y1-expressing neurons to suppress light punctate touch and mechanical itch stimuli. NPY-Y1 signaling thus regulates the transmission of innocuous tactile information by establishing biologically relevant thresholds for touch discrimination and mechanical itch reflexes.

Keywords: NPY1R signaling; Y1 excitatory neurons; chemical itch; dorsal spinal cord; inhibition; mechanical itch transmission; neuropeptide Y; pain; somatosensory processing; touch.

Publication types

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

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Mechanoreceptors / metabolism
  • Mechanoreceptors / physiology*
  • Mice
  • Mice, Knockout
  • Neuropeptide Y / metabolism*
  • Neuropeptide Y / physiology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism
  • Posterior Horn Cells / physiology*
  • Receptors, Neuropeptide Y / metabolism*
  • Reflex / physiology
  • Sensory System Agents / pharmacology
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Spinal Cord / physiology
  • Stimulation, Chemical


  • Neuropeptide Y
  • Receptors, Neuropeptide Y
  • Sensory System Agents
  • neuropeptide Y-Y1 receptor
  • Clozapine
  • clozapine N-oxide
  • Capsaicin