DMS Home  /  About DMS  /  Current Student Resources  /  Contact Us  /  Search 

Ru-Rong Ji, Ph.D.

Assistant Professor of Anesthesiology

Brigham & Women's Hospital
Medical Research Building
Boston, MA 02115
Telephone: 617-732-8852
Email: rrji@zeus.bwh.harvard.edu
Predoc: 0 Postdoc: 4 Completed PhD's: 0

 

Chronic pain, such as neural injury-associated neuropathic pain, is a major public health problem in the world. Current treatment for this pain only has limited success due to our incomplete understanding of the mechanisms underlying the induction and maintenance of chronic pain. It is generally believed that chronic pain is an expression of neural plasticity in the pain pathway.  Although pain was regarded as “neuron-mediated”, recent evidence suggests that glial cells in the spinal cord play an important role in the development and maintenance of chronic pain. Using well-characterized animal models of neuropathic pain, we found that three MAP kinase family members are activated in different types of spinal glial cells after an injury to the peripheral axons (e.g., spinal nerve or sciatic nerve) of primary sensory neurons. For example, p38 is only activated in spinal microglia at early times of injury, JNK is persistently activated in spinal astrocytes, and ERK is activated first in spinal microglia and then in spinal astrocytes. Importantly, blocking these kinases in the spinal cord can attenuate neuropathic pain. We hypothesize that neural-glial interaction is essential for chronic pain sensitization. We have been trying to answer the following questions: (1) how neural signal (e.g., electrical activity, release of chemokines and proteinases) in primary sensory neurons is conveyed to glial cells in the spinal cord after peripheral axonal injury, (2) how glial signal (e.g., release of cytokines and growth factors) gets back to spinal neurons to cause sensitization of these neurons, and (3) how microglia and astrocytes differentially regulate chronic pain (e.g., induction vs maintenance of chronic pain). We are using histochemical, biochemical, imaging, electrophysiological, and behavioral approaches in intact animals or in isolated spinal cord slices to answer these questions. 

 

 

References:

  • Jin SX, Zhuang ZY, Woolf CJ, and Ji RR. p38 MAPK is activated after spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. Journal of Neuroscience 2003; 23:4017-4022.

    Ji RR, Kohno T, Moore KA, and Woolf CJ. Central sensitization and long-term potentiation - do pain and memory share similar mechanisms? Trends in Neuroscience, 2003; 26: 696-705.

    Ji RR, Strichartz G. Cell signaling and the genesis of neuropathic pain. Science’ STKE, 2004; 252:reE14.

    Zhuang ZY, Gerner P, Woolf CJ, Ji RR. ERK is sequentially activated in neurons, microglia, and astroglia by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain, 2005, 114:149-59.

    Zhuang ZY, Wen YR, Zhang DR, Tiziana B, Christhophe B, Strichartz GR, Decosterd I, Ji RR. A peptide JNK inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance. Journal of Neuroscience, 2006; 26:3551-3560.