Pain and itch are distinct sensations that significantly affect the quality of life. Their underlying mechanisms continues to be a major challenge for neuroscientists. The aim of this special issue is to provide the most recent investigations of pain and itch. On the cover of this special issue, Tong et al. reveal the potential role of the autonomic nervous system in itch formation in cutaneous T-cell lymphoma (CTCL). The cover image shows a patient with CTCL suffering from severe itch. The sympathetic nerve works like an evil hand that viciously changes naive glial cells of the spinal cord into monsters and leads to the formation of cancer-associated itch. See pages 435–439. (Cover provided by Dr. Qingjian Han)