Circuit dissection of the role of somatostatin in itch and pain

Nat Neurosci. 2018 May;21(5):707-716. doi: 10.1038/s41593-018-0119-z. Epub 2018 Mar 19.


Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide.

Publication types

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

MeSH terms

  • Animals
  • Dynorphins / metabolism
  • Female
  • Ganglia, Spinal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiopathology*
  • Optogenetics
  • Pain / metabolism
  • Pain / physiopathology*
  • Pruritus / metabolism
  • Pruritus / physiopathology*
  • Receptors, Atrial Natriuretic Factor / biosynthesis
  • Receptors, Atrial Natriuretic Factor / metabolism
  • Receptors, Purinergic / metabolism
  • Receptors, Somatostatin / antagonists & inhibitors
  • Receptors, Somatostatin / genetics
  • Sensory Receptor Cells
  • Somatostatin / biosynthesis
  • Somatostatin / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / physiopathology


  • Receptors, Purinergic
  • Receptors, Somatostatin
  • somatostatin receptor 2, mouse
  • Somatostatin
  • Dynorphins
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor B