Following upon our extensive earlier studies of the CNS circuits through which opioids exert their analgesic effects, our laboratory now examines the mechanisms through which tissue and nerve injury produce changes in the peripheral and central nervous system that result in persistent pain. In parallel studies, we examine the circuits through which pruritogens generate itch. The hallmark of our work is a multidisciplinary approach to the problem, using molecular, neuroanatomical, pharmacological and behavioral analyses in wild type, and genetically-modified mice, including knockouts and Cre- or reporter-expressing mice. By combining these studies with an analysis of the functional properties of molecularly-defined neurons, these studies examine the extent to which pain and itch circuits segregate or converge at the level of spinal cord interneurons and projection neurons. In recent studies, we turned our attention to the possibility of overcoming the neurological consequences of peripheral nerve damage, by transplanting embryonic cortical GABAergic precursor cells into the spinal cord. We have demonstrated that the cells integrate synaptically and functionally into host neural circuits and can ameliorate the persistent pain and itch associated with nerve damage. Very recently, we have significantly expanded the scope of our studies. We are using calcium imaging of cortical neurons in awake mice to examine the brain circuits and mechanisms through which pain and itch percepts are generated as well as the mechanisms through which general anesthetics exert their analgesic action.