Dr. Tony L. Yaksh: Purdue University (PhD 1971), U.S. Army (1971-73), University of Wisconsin (1973-76), University College London (1976-77), Mayo Clinic, Rochester, MN (1977-1988).  He is Professor in Anesthesiology at UC San Diego (1988-present).  His studies (> 800 papers) provide a basis for understanding the pharmacology of pain processing.   He has >46,000 citations in >26,000 papers. He has mentored over 100 postdoctoral trainees and has been funded consistently by NIH since 1977.  He has received many awards including from the American Pain Society, the International Association for the Study of Pain and the Swedish Society of Medicine. He has twice received the Javitz award. My laboratory at Mayo Clinic (1976 to 1988) and at the University of California San Diego (1989 - present) has been continuously involved in NIH-supported research on the mechanisms of pain and analgesia. A continuing thread of this ongoing work has first been the role of lipid mediators in pain processing and more specifically the contribution of innate immunity in spinal systems. A continuing thread of this ongoing work (>20 papers) has been the contribution of inflammatory cascades and innate immunity in these spinal systems. Our group, in an extensive collaboration with Dr. Maripat Corr at UCSD demonstrated that KO of TLR4 signaling and spinal TLR4 blockers prevented the transition from an acute inflammation to a chronic neuropathic like pain state and the differential role of sex in this cascade. Our recent work looking at cell specific KO of an important link in this signaling cascade emphasize the importance of this cascade in the development of a chronic pain state. I look forward to working with Dr. Corr in pursuing the work outlined in this proposal. We have an established track record of productive collaboration and co-mentoring students and fellows.