Serotoninergic projection from dorsal raphe nucleus to insular cortex is involved in acute itch sensation processing in mice

Previous studies have demonstrated that both dorsal raphe nucleus (DR) and insular cortex (IC) are critical for somatic sensory information transmission and regulation, especially for pain, and neurons in the DR send projection fibers to the IC. However, whether these ascending connections are involved in the processing of itch sensation remains unknown. In order to provide evidence for that, fluoro-gold (FG) retrograde tracing combined with immunofluorescent histochemical staining was performed for revealing the chemical nature of the projection neurons and the FOS expression induced by acute itch stimulation via intradermal histamine or chloroquine injection in the mouse. Both FOS- and p-ERK-containing neurons were increased in the DR and IC in the acute itch mice compared to those in the sham group. After FG was injected into the IC, FG-labeled retrograde neuronal cell bodies were observed in the whole extent of the brainstem, especially in the DR. About 81% of the total number of FG-labeled neurons in the DR showed serotonin (5-HT)-immunopositive staining. About 32% FG-labeled 5-HT-ergic neurons within DR expressed FOS in chroloquine-induced acute itch, whereas only 6% FG-labeled 5-HT-ergic neurons within DR expressed FOS in histamine-induced acute itch. These results provide morphological evidence for that there are 5-HT-ergic projections from the DR to IC which might be involved in the sensory information processing of acute itch. These results are helpful for understanding functional roles of 5-HT-ergic ascending projection under the condition of acute itch.