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 generated in our laboratory. 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. Also of great interest are the mechanisms through which monocytes, including peripheral macrophages and spinal cord microglia, contribute to the persistent pain following nerve injury. With a view to overcoming the neurological consequences of peripheral nerve damage, we also studied the effects of 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, effectively treating what we consider to be the "disease" of neuropathic pain. And recently using long-term calcium imaging of spinal cord and cortical neurons in awake, behaving mice we are examining the brain and spinal cord circuits and mechanisms through which pain and itch percepts are generated as well as the mechanisms through which different general anesthetics exert their analgesic action. Below are several comprehensive reviews that we have published on the topics described above.