Chronic Pain of Neuropathic Origin
The Patti laboratory is interested in neuropathic pain, a chronic pain state that results from peripheral and/or central nerve injury. By using cutting-edge metabolomic technologies, we have identified a novel sphingolipid, N,N-dimethylsphingosine (DMS), that is increased in the dorsal horn of patients suffering from neuropathic pain and is sufficient in itself to induce pain-like behaviors when administered intrathecally in healthy animals. A major effort in our laboratory is to identify the metabolic pathways and specific enzymes involved in DMS biosynthesis as well as the biochemical mechanism(s) by which DMS elicits pain-like behavior. Based on preliminary data showing that DMS results in cytokine release from astrocytes in vitro, we are interested in dissecting the role of astrocytes in the neuropathic pain state and the metabolic interrelationships with other surrounding cell types that may be influenced by alterations in sphingolipid production. Our current working model in which DMS is released from oligodendrocytes upon damage to activate a signaling cascade via astrocytes is shown below.