Altered expression of itch-related mediators in the lower cervical spinal cord in mouse models of two types of chronic itch

Abstract

In this study, we focused on several itch-related molecules and receptors in the spinal cord with the goal of clarifying the specific mediators that regulate itch sensation. We investigated the involvement of serotonin receptors, opioid receptors, glia cell markers and chemokines (ligands and receptors) in models of acetone/ether/water (AEW)- and diphenylcyclopropenone (DCP)-induced chronic itch. Using reverse transcription-quantitative polymerase chain reaction, we examined the expression profiles of these mediators in the lower cervical spinal cord (C5-8) of two models of chronic itch. We found that the gene expression levels of opioid receptor mu 1 (Oprm1), 5-hydroxytryptamine receptor 1A (Htr1a) and 5-hydroxytryptamine receptor 6 (Htr6) were upregulated. Among the chemokines, the expression levels of C-C motif chemokine ligand (Ccl)21, Cxcl3 and Cxcl16 and their receptors, Ccr7, Cxcr2 and Cxcr6, were simultaneously upregulated in the spinal cords of the mice in both models of chronic itch. By contrast, the expression levels of Ccl2, Ccl3, Ccl4 and Ccl22 were downregulated. These findings indicate that multiple mediators, such as chemokines in the spinal cord, are altered and may be central candidates in further research into the mechanisms involved in the development of chronic itch.