As chronic pain is a severe problem in clinics, study of the mechanisms of chronic pain and development of novel analgesic agents is of significance. In the past decade, our lab completed a series of studies on the regulatory mechanisms of functional sensitization and membrane trafficking of transient receptor potential vanilloid type 1 (TRPV1), a key molecule involved in the development of peripheral sensitization. Our studies elucidated the important regulatory roles of several protein kinases, including PKD1 (protein kinase D1), Cdk5 (cyclin-dependent kinase 5) and LIMK (LIM-motif containing kinase), in inflammatory thermal hyperalgesia. Moreover, based on these findings, we constructed a series of transmembrane Tat-fusion peptides for pain relief. The potential role of central TRPV1 was discussed as well. Prelimbic subregion of prefrontal cortex was revealed to be a critical brain region involved in the interaction between pain sensation and pain emotions by our recent studies. In addition, our work attempted to improve the analgesic effects of the agents targeting TRPV1 and concurrently reduce their side effects. Herein we summarized the work of our lab in pain and pain modulation during the past decade.