Dr. Levine’s Research Synopsis: Our laboratory employs a multidisciplinary approach molecular, biochemical, in vitro and in vivo electrophysiological and behavioral techniques are employed to evaluate mechanisms underlying pain and analgesia. We are investigating signal transduction mechanisms for mechanical, thermal and chemical stimulus-induced activation of sensory neurons and mechanisms underlying sensitization of responses to these stimuli. We have recently described novel transducer mechanisms for thermal stimuli. We have also described a second messenger pathway mediating sensitization. The modulation of transduction by opioids is also being investigated, including the mechanisms underlying opioid tolerance and dependence. We also investigate circuits that mediate analgesia and have recently described a novel analgesia circuit involving limbic pathways as well as sexual dimorphism in pain and analgesic mechanisms. Finally, we are investigating neural and endocrine contributions to inflammation and to the immune response. Our recent work has elucidated a physiological mechanism consisting of a negative feedback inhibition of the inflammatory response, involving neural and endocrine circuits.