Undoubtedly, pain conditions the quality of life of millions of people worldwide suffering a wide range of diseases. Major research efforts are being made by the international scientific community to determine the mechanisms underlying nociception. Growing evidence points out a complex network including oxidative and nitrosative stress, inflammatory response and cation signaling. In this sense, transient receptor potential (TRP) channels have attracted researchers' attention. Expression levels are very different in tissues and cells mediating a myriad of processes in our organism. At the neurological level, it has been observed that the expression levels of four TRP channels (TRPA1, TRPM2, TRPV1, and TRPV4) are high in neurons related to nociception, including dorsal root ganglion and trigeminal ganglia neurons. For this reason, this research field promises to shed light on this intricated matrix linking oxidative stress, calcium signaling (via TRP channels), and inflammatory signals in different pain modalities, including neuropathic pain and chemotherapy-induced peripheral pain. In such a way, all this intense research activity will enable us to design individual and rational treatment strategies for pain relief, such as the use of molecular neurosurgery.