A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Akiyama, Tasuku; Nguyen, Tony; Curtis, Eric; Nishida, Katsuko; Devireddy, Jahnavi; Delahanty, Jeremy; Carstens, Mirela Iodi; Carstens, Earl
• Is Part Of: Pain. Volume 156:Issue 7(2015)
• Publication Date: 2015-07
• Subjects: Atopic dermatitis -- Chronic itch -- Central sensitization -- Alloknesis -- Hyperknesis -- Substance P -- Neurokinin-1 receptor -- Gastrin-releasing peptide receptor; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000000172
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : 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 bombesin-saporin (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. Abstract : Mice sensitized with ovalbumin developed dermatitis and behavioral signs of chronic itch that are mediated by ascending spinal projection neurons that express the neurokinin-1 receptor.