Our laboratory investigates the mechanisms through which inflammation, nerve injury, or CNS disease produces neurochemical changes and plasticity in peripheral nerve, spinal cord, and brain, leading to a transition from acute pain to chronic pain. We explore innovative ideas using optogenetic stimulation and GCaMP imaging of selected neuronal or glial populations, behavioral pharmacology, and immunohistochemistry to better understand the molecular neurobiology of pain sensitization and opioid dependence. Our goal is to contribute to new pharmacotherapeutic approaches for the development of analgesic drugs. We have several ongoing projects: 1. We reported in Science that mu-opioid receptor (MOR) inverse agonists, when delivered long after the resolution of acute pain, could reliably, repeatedly, and robustly reinstate hyperalgesia, affective pain, spontaneous pain, molecular and neurophysiological markers of spinal pain transmission, and, remarkably, behavioral signs of opioid withdrawal. These studies suggested that tissue injury triggers two previously undescribed phenomenon: MOR constitutive activity (which we have coined MORCA), and “endogenous opioid dependence”. We are currently asking how MORCA prevents that pathological manifestations of latent neuronal pain sensitization, studying the cellular signaling pathways of latent sensitization, and launching a project to determine the neurobiological basis of endogenous opioid dependence in the brain; 2. We reported in PNAS that endogenous neuropeptide Y tonically inhibits chronic pain. Current studies are investigating mechanisms of NPY release and the dorsal horn circuitry of the NPY Y1 receptor-containing neuron; 3. In 2006 we discovered a new target in the dorsal horn for the pharmacotherapy of chronic pain -- the peroxisome proliferator-activated receptor gamma, using PPARg drugs that are currently FDA approved to treat diabetes. Current studies are exploring mechanisms of painful diabetic neuropathy in the peripheral nerve and spinal cord.
Summer Undergraduate Research Program
- Doolen S, Iannitti T., Donahue RR, Shaw BC, Grachen CM, and Taylor BK. Fingolimod reduces neuropathic pain in a mouse model of multiple sclerosis by a sphingosine-1-phosphate receptor 1-dependent inhibition of central sensitization in the dorsal horn. Pain, Nov 13 Epub ahead of print, (2017).
- Doolen S*., Cook, J*., Riedle, M., Kitto, K., Kohsaka, S., Honda, CN., Fairbanks, CA, Taylor, B.K+, Vulchanova, L.+Complement3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling. Glia. Epub Aug 29. (2017). *co-first authors. +co-senior authors.
- Griggs, R.B., Donahue, R.R., Morgenweck, J., Grace, P.M., Sutton, A., Watkins, L.R., and Taylor, B.K. Pioglitazone rapidly reduces neuropathic pain through astrocyte and nongenomic PPARg mechanisms. Pain 156:469-82 (2015).
- G. Corder, S. Doolen, R. R. Donahue, M.K. Winter, B.L. Jutras, Y. He, X. Hu, J.S. Wieskopf, J.S. Mogil, D.R. Storm, Z.J. Wang, K.E. McCarson, and B.K. Taylor. Constitutive µ-Opioid Receptor Activity Leads to Long-term Endogenous Analgesia and Dependence. Science 341: 1394-1399 (2013). Top Science Advance in Pain Research, 2012-2013”, NIH Interagency Pain Research Coordinating Committee (IPRCC).
- Solway, B., Bose, S., Corder, G., Donahue, R., and Taylor, B.K. Tonic inhibition of chronic pain by Neuropeptide Y. Proceedings of the National Academy of Sciences 108:7224-9 (2011).