TRPV1 is an important analgesia target. Capsaicin, the prototypical TRPV1 agonist, has a clear therapeutic potential. But the highly pungency limited its use. In this letter, for lowering its pungency, a series of capsaicin derivatives were designed and synthesized, including 10 compounds which were the direct combination of capsaicin and dihydro capsaicin with various NSAIDs. Preliminary biological tests suggested that some compounds had both anti-inflammatory activity and analgesic activity and their pungency was lower. Based on these results, some of these molecules can be considered as lead candidates for the further development of analgesic drugs.