goldengate

Our laboratory examines the mechanisms through which tissue and nerve injury produce changes in the peripheral and central nervous system, resulting in persistent pain. In parallel studies we are examining the circuits through which pruritogens generate itch.

These studies follow upon our recent work that defined mechanisms through which opioids that act at different receptor subtypes exert their pain relieving effects. The hallmark of our work is our laboratory’s multidisciplinary approach to the problem, using molecular, neuroanatomical, pharmacological and behavioral analyses in wild type and genetically modified mice. Many of these mice, including knockouts and Cre- or reporter-expressing mice are generated in our laboratory. To expand our analyses using our transgenic mouse in which wheat germ agglutinin transneuronal labeling of complex circuits can be triggered from neurons in any region of the brain or spinal cord, we now incorporate transneuronal anterograde (herpes) and retrograde (rabies) viral tracers in our circuit analyses.

These studies are integrated with functional analyses of the labeled neurons. These studies will examine the extent to which pain and itch circuits are segregated or convergent at the level of spinal cord interneurons and projection neurons. Most recently, 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 into the host and can ameliorate the persistent pain and itch associated with nerve damage.