Distinct roles of NMB and GRP in itch transmission

Sci Rep. 2017 Nov 13;7(1):15466. doi: 10.1038/s41598-017-15756-0.

Abstract

A key question in our understanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter. Neuromedin B (NMB) is a mammalian member of the bombesin family of peptides closely related to GRP, but its role in itch is unclear. Here, we show that itch deficits in mice lacking NMB or GRP are non-redundant and Nmb/Grp double KO (DKO) mice displayed additive deficits. Furthermore, both Nmb/Grp and Nmbr/Grpr DKO mice responded normally to a wide array of noxious stimuli. Ablation of NMBR neurons partially attenuated peripherally induced itch without compromising nociceptive processing. Importantly, electrophysiological studies suggested that GRPR neurons receive glutamatergic input from NMBR neurons. Thus, we propose that NMB and GRP may transmit discrete itch information and NMBR neurons are an integral part of neural circuits for itch in the spinal cord.

Publication types

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

MeSH terms

  • Animals
  • Antipruritics / administration & dosage
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Capsaicin / administration & dosage
  • Disease Models, Animal
  • Gastrin-Releasing Peptide / genetics
  • Gastrin-Releasing Peptide / metabolism*
  • Histamine / administration & dosage
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurokinin B / analogs & derivatives*
  • Neurokinin B / genetics
  • Neurokinin B / metabolism
  • Nociception / drug effects
  • Nociception / physiology
  • Nociceptors / metabolism
  • Pruritus / chemically induced
  • Pruritus / drug therapy
  • Pruritus / pathology*
  • Receptors, Bombesin / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Skin / drug effects
  • Skin / innervation
  • Skin / pathology
  • Spinal Cord / cytology
  • Spinal Cord / metabolism

Substances

  • Antipruritics
  • Receptors, Bombesin
  • Gastrin-Releasing Peptide
  • Histamine
  • Neurokinin B
  • neuromedin B
  • Capsaicin