Ru Rong Ji, PhD, PI
We investigate the molecular and cellular mechanisms underlying the induction, maintenance, and resolution of persistent pain. We focus on spinal cord synaptic transmission and the role of glial cells. We use a range of molecular, cellular, electrophysiological, and behavioral approaches in transgenic mice.
Pain Signaling and Sensory Plasticity Laboratory
Chronic pain is a major health problem in the US affecting 100 million Americans, but the current treatments for chronic pain are inadequate. The main goal of the lab is to identify novel molecular and cellular mechanisms that underlie the genesis of chronic pain. Recently, we also began to explore the mechanisms underlying the resolution of acute pain, and these mechanisms are responsible for the transition from acute pain to chronic pain. Very recently, we became interested in distinct molecular mechanisms of pain and itch. We employ a multidisciplinary approach that covers in vitro, ex vivo, and in vivo electrophysiology, neuronal and glial cell biology, transgenic mice, and behaviors. We believe that tackling the mechanisms of pain induction and resolution will lead to the development of novel therapeutics for chronic pain and itch.
Major research interests:
Pathogenesis of pain via neural-glial interactions: We investigate (1) how neural signals (e.g., electrical activity and release of proteases) in primary sensory neurons cause the activation of glial cells (microglia and astrocytes) in the spinal cord after tissue and nerve injury, and (2) how glia mediators (e.g., cytokines and chemokines) modulate spinal cord synaptic transmission. We have demonstrated that distinct activation MAPK signaling pathways (ERK, p38, and JNK) in spinal cord microglia and astrocytes is critical for the development of neuropathic pain. We have also demonstrated that proinflammatory cytokines and chemokines (e.g., TNF-a, IL-1b, and MCP-1) can powerfully modulate synaptic transmission in the spinal cord, by enhancing excitatory synaptic transmission and suppressing inhibitory synaptic transmission.
Resolution of pain by anti-inflammatory and pro-resolution mediators: We investigate how lipid mediators, such as resolvins and neuroprotectins, and marresins, derived from omega-3 unsaturated fatty acids control pain by (1) blocking TRP channels, (2) resolving synaptic plasticity, and (3) inhibit inflammation and glial activation. We have shown that resolvins are among the most potent inhibitors for inflammatory pain and TRP channels. We also determine the down-stream GPCR signaling that mediates the potent actions of these lipid mediators.
Molecular mechanisms of itch: We investigate how toll-like receptors (TLRs) and oxidative stress regulate acute and chronic itch. We found an unconventional and non-transcriptional role of TLRs: TLRs (e.g., TLR3 and TLR7), expressed by primary sensory neurons, contribute to itch by modulating excitability of primary sensory neurons and spinal cord synaptic transmission. We now determine the functional coupling of TLRs and ion channels.