Background: Chronic pruritus is a symptom that commonly observed in neurological diseases. It has been hypothesized that the chronic pruritus may result from sensitization of itch-signaling pathways but the mechanisms remain obscure.Methods: In this study, we established a mouse model of chronic compression of dorsal root ganglion (CCD) and injected various pruritogenic and algogenic agents intradermally to the calf skin ipsilateral to the compressed DRG. We additionally investigated if

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... en-evoked activities of dorsal root ganglion (DRG) neurons is enhanced in this model. The expression of TRPV1, CGRP and H1R was detected with immunoflorescent staining. DRG neurons response to four agents using in vivo calcium imaging.Results: Compared to the naïve mice, a significant increase in itch-related behaviors was observed in the CCD mice after the injection of pruritogens including histamine and BAM8-22, but not after the injection of algogenic agents including capsaicine and 5-HT, although all the above agents evoked enhanced pain-related behaviors toward the injected site. In vivo calcium imaging revealed that compressed DRG neurons exhibited significantly enhanced responses to histamine and BAM8-22. Immunoflorescent staining also showed that the histamine receptor H1 and the capsaicin receptor TRPV1 were significantly upregulated in DRG neurons.Conclusions: Our findings indicated that sensitization of primary pruriceptive neurons may underlie the enhanced itch sensation after chronic compression of DRG neurons in mice, and may play a role in chronic pruritus in neurological diseases.