Ru-Rong Ji, Ph.D.

Associate Professor of Anesthesiology

Brigham & Women's Hospital
Medical Research Building, Room 502
Boston, MA 02115
Telephone: 617-732-8852
Email: rrji@zeus.bwh.harvard.edu

Chronic pain, such as neural injury-associated neuropathic pain, is a major public health problem in the world. Current treatments 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 MAP kinase family members (e.g., ERK, p38, and JNK) are activated in different types of spinal glial cells (e.g., microglia and astrocytes) after peripheral nerve injury and required for neuropathic pain sensitization.  We hypothesize that activation of MAP kinase pathways in glial cells contribute to chronic pain sensitization via neural-glial interations.

We have been trying to answer the following questions:  (1) how neural signals (e.g., electrical activity, release of chemokines and proteinases) from primary sensory neurons activate microglia and astrocytes in teh spinal cord after peripheral axonal injury, (2) how glial cells produce pain mediators (e.g., cytokines and chemokines), and (3) how glial mediators (e.g., cytokines and chemokines) regulate synaptic plasticity in teh spinal cord as well as chronic pain behaviors.

We employ behavioral assays to measure pain-like behaviors in animal models of inflammatory pain, neuropathic pain, and cancer pain.  We use electrophysiology (e.g., patch clamp recordings in spinal slices) to examine synaptic plasticity in the spinal cord.  We prepare primary cultures to study signal transduction in primary sensory neurons, microglia, and astrocytes.

References:

• Ji RR, Suter MR.  (2007) p38 MAPK, microglial signaling, and neuropathic pain.  Mol. Pain 3:33.  Review.

• Kawasaki Y, Xu ZZ, Wang X, Park JY, Zhuang ZY, Tan PH, Gao YJ, Roy K, Corfas G, Lo EH, Ji RR.  (2008)  Distinct roles of matrix metalloproteases in teh early- and late-phase development of neuropathic pain.  Nature Med.  14:331-336.
• Kawasaki Y, Zhang L, Cheng JK, Ji RR (2008)  Cytokine mechanisms of central sensitization:  Overlapping and distinct roles of proinflammatory cytokines IL-1ß, IL-6, and TNF-œ in regulating synaptic and neuronal activity.  J. Neurosci 28:5189-5194.
• Gao YJ, Zhang L, Samad OA, Suter MR, Yasuhiko K, Xu ZZ, Park JY, Lind AL, Ma Q, Ji RR.  (2009)  JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.  J. Neurosci. 29:4096-108.
• Ji RR, Gereau RW, Malcangio M, Strichartz GR.  (2009).  MAP kinase and pain.  Brain Res. Rev. 60:135-48.

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