Cancer-associated itch can be described as pruritus associated with malignancy. Although intractable itch associated with specific types of cancer afflicts patients badly, few effective treatments are available due to limited knowledge about the mechanisms of such itch. Globally, cancer-associated itch is an uncommon symptom in malignancy; its incidence among the whole cancer population is just 10%[1], but in specific categories of cancer such as a polycythemia vera, lymphoma, and non-melanoma skin cancer, the itch ratio can reach 60%[2]. One typical subtype of itch-associated malignancy is cutaneous T-cell lymphoma (CTCL), which is pathologically characterized by the abnormal accumulation of malignant T-cells in the skin, potentially resulting in the development of rashes, plaques, and especially a high incidence of severe itch [3]. These properties make CTCL an ideal candidate for generating a mouse model of cancer-associated itch. In a previous study, we established a CTCL cancer-associated itch mouse model by inoculating CD4? Myla cells derived from tumor tissue from CTCL patients intradermally into the nape of the neck, and found that the miR-711 released from malignant cells can elicits peripheral itch [4]. However, neutralizing or blocking miR-711 just partially attenuates the CTCL-associated itch [4], suggesting that other mechanisms are involved in cancer-associated itch. The hapten 2, 4-dinitrofluorobenzene (DNFB) is a contact skin sensitizer that has been reported to have a tumorpromoting effect when applied to the tumor-forming region [5]. We improved the previous CTCL mouse model by painting 0.5% DNFB on the nape of the neck 24 h after inoculation of CD4? Myla cells; this caused the tumorforming ratio increase from-60% to-90%(Fig. 1 A–C). Topical application of DNFB induces skin inflammation characterized by high dynamic transcriptional change of pro-inflammatory cytokines, Gr-1 (high) neutrophils, and F4/80 (?) macrophage infiltration, which can improve all stages of cancer [6]. So DNFB application mimics the clinical condition of a tumor with inflammation. We allowed the tumor grow for 40 days, and at about day 20, we observe an obvious skin lesion at the center of the tumor (Fig. 1 B). Consistent with the previous CTCL mouse model, severe itch developed from 5 days after Myla cell inoculation; its intensity was reduced at day 20; recovered at day 30; and increased continuously later on (Fig. 1 H). One possible reason for the reduction of itch intensity at day 20 may be that the excessive tumor growth resulted in nerve injury, and the resulting pain masked the itch. To investigate the central mechanism of cancer-associated itch, we checked the glial activation in the cervical