Spinal bombesin-recognized neurones mediate more nonhistaminergic than histaminergic sensation of itch in mice

Clin Exp Dermatol. 2012 Apr;37(3):290-5. doi: 10.1111/j.1365-2230.2011.04314.x. Epub 2012 Feb 14.

Abstract

Background: There may be distinct pathways for transmission of histaminergic and nonhistaminergic itch, but all scratching behaviours elicited by histamine-dependent and histamine-independent pruritogens are diminished when spinal bombesin-recognized neurones are ablated.

Aim: To investigate whether there is a difference in transmission of spinal itch signals between histamine-induced itch and nonhistamine-induced itch after neurotoxic destruction of spinal bombesin-recognized neurones.

Methods: To ascertain the different relevance of spinal bombesin-recognized neurones in transmission of itch signals between these two classes of pruritogens, we determined the distribution of Fos-positive cells in the dorsal horn of spinal cord after stimulation with histamine (500 μg/site) and chloroquine (200 μg/site) in mice with spinal bombesin-recognized neurones ablated by intrathecal injection of bombesin-saporin (400 ng/5 μL).

Results: We found that after stimulation with both histamine and chloroquine, fewer Fos-positive cells were present in mice treated with bombesin-saporin compared with those treated with saporin alone. The reduction in Fos expression was greater with chloroquine than with histamine, and the distribution of Fos-positive cells was also different. We used biotin-labelled isolectin (IB)4, which labels one subset of C-fibres, and found that the percentages of Fos-positive cells in three areas (the dorsal to IB4-labelled region, the IB4-labelled region itself, and the ventral to IB4-labelled region) all changed significantly after intradermal injection of chloroquine, but not histamine, in mice treated with bombesin-saporin.

Conclusions: These results suggest that spinal bombesin-recognized neurones are critical to both the histamine-dependent and histamine-independent pathways for itch, and that they mediate more nonhistaminergic than histaminergic sensation of itch in mice.

MeSH terms

  • Animals
  • Bombesin / administration & dosage
  • Chloroquine / pharmacology
  • Denervation / methods
  • Histamine / pharmacology
  • Histamine Agonists / pharmacology*
  • Hypersensitivity / metabolism
  • Hypersensitivity / physiopathology
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurotransmitter Agents / administration & dosage
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Pruritus / chemically induced
  • Pruritus / physiopathology*
  • Receptors, Bombesin / metabolism
  • Ribosome Inactivating Proteins, Type 1 / administration & dosage
  • Saporins
  • Skin / innervation
  • Synaptic Transmission / physiology

Substances

  • Histamine Agonists
  • Neurotransmitter Agents
  • Proto-Oncogene Proteins c-fos
  • Receptors, Bombesin
  • Ribosome Inactivating Proteins, Type 1
  • Histamine
  • Chloroquine
  • Saporins
  • Bombesin