Our laboratory investigates the mechanisms through which inflammation or injury produces changes in the peripheral nerves, spinal cord, and brain, leading to a transition from acute pain to chronic pain. We explore innovative ideas using state-of-the art techniques to better understand the molecular neurobiology of pain sensitization and opioid dependence, and thus contribute to new pharmacotherapeutic approaches to the development of analgesic drugs.
Recently, we reported in Science that long-lasting activity at endogenous mu-opioid receptors inhibits multiple signs of chronic pain. We found that inverse agonists reinstate hyperalgesia, affective pain, spontaneous pain, and molecular and neurophysiological markers of spinal pain transmission when delivered long after the induction and resolution of acute pain. These studies suggested that constitutive activity at mu opioid receptor maintains hyperalgesia in a state of remission, and are now funded through 2020. We have also reported in PNAS that endogenous neuropeptide Y tonically inhibits chronic pain, perhaps by a completely different mechanism involving a ligand-induced activation of NPY receptors (rather than constitutive activity at opioid receptors), and the R01 was just renewed again to continue these studies through 2021. Also, in 2006 we discovered a new target for the pharmacotherapy of chronic pain including painful diabetic neuropathy, the peroxisome proliferator-activated receptor gamma in the dorsal horn, and the R01 was just renewed again to continue these studies through 2022.