A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch

Tasuku Akiyama, Tony Nguyen, Eric Curtis, Katsuko Nishida, Jahnavi Devireddy, Jeremy Delahanty, Mirela Iodi Carstens, Earl Carstens

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

We investigated roles for spinal neurons expressing the neurokinin-1 receptor (NK1R) and/or gastrin-releasing peptide receptor (GRPR) in a mouse model of ovalbumin (OVA)-induced chronic atopic dermatitis. Mice receiving repeated topical application of OVA exhibited atopic-like skin lesions and behavioral signs of chronic itch including spontaneous scratching, touch-evoked scratching (alloknesis), and enhancement of chloroquine-evoked scratching (hyperknesis). Substance P-saporin (SP-SAP) and bombesinsaporin (BB-SAP) were intrathecally injected into OVA-sensitized mice to neurotoxically ablate NK1R- or GRPR-expressing spinal neurons, respectively. SP-SAP diminished the expression of NK1R in the superficial spinal dorsal horn and significantly attenuated all behavioral signs of chronic itch. BB-SAP reduced the spinal dorsal horn expression of GRPR and significantly attenuated hyperknesis, with no effect on spontaneous scratching or alloknesis. To investigate whether NK1R-expressing spinal neurons project in ascending somatosensory pathways, we performed a double-label study. The retrograde tracer, Fluorogold (FG), was injected into either the somatosensory thalamus or lateral parabrachial nucleus. In the upper cervical (C1-2) spinal cord, most neurons retrogradely labeled with FG were located in the dorsomedial aspect of the superficial dorsal horn. Of FG-labeled spinal neurons, 89% to 94% were double labeled for NK1R. These results indicate that NK1R-expressing spinal neurons play a major role in the expression of symptoms of chronic itch and give rise to ascending somatosensory projections. Gastrin-releasing peptide receptor-expressing spinal neurons contribute to hyperknesis but not to alloknesis or ongoing itch. NK1R-expressing spinal neurons represent a potential target to treat chronic itch.

Original languageEnglish (US)
Pages (from-to)1240-1246
Number of pages7
JournalPain
Volume156
Issue number7
DOIs
StatePublished - Jul 2015
Externally publishedYes

Keywords

  • Alloknesis
  • Atopic dermatitis
  • Central sensitization
  • Chronic itch
  • Gastrin-releasing peptide receptor
  • Hyperknesis
  • Neurokinin-1 receptor
  • Substance P

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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  • Cite this

    Akiyama, T., Nguyen, T., Curtis, E., Nishida, K., Devireddy, J., Delahanty, J., Carstens, M. I., & Carstens, E. (2015). A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch. Pain, 156(7), 1240-1246. https://doi.org/10.1097/j.pain.0000000000000172