Sensory Plasticity and Pain Research Laboratory

Sensory Plasticity and Pain Research Lab

Lab Description

Chronic pain is a major health problem in the US and affects 100 million Americans, but the current treatments for chronic pain are inadequate. The current epidemic of opioid abuse is a result of lack of efficient pain medicine.  The main goal of the lab is to identify novel molecular and cellular mechanisms that underlie the genesis of chronic pain. We employ a multidisciplinary approach that covers in vitro, ex vivo, and in vivo electrophysiology, cell biology of glial cells, immune cells, and cancer cells, transgenic mice, and mouse behaviors of various sensory modalities after inflammation, nerve injury, and cancers. We believe that tackling the mechanisms of pain induction and resolution will lead to the development of novel therapeutics for preventing and treating chronic pain.

Pain and itch regulation by non-neuronal cells and inflammationPain and Itch Regulation by Non-Neuronal Cells and Inflammation [PMID: 27811267]

  • On a cellular level, we investigate how non-neuronal cells such as glial cells, immune cells, stem cells, and cancer cells contribute to acute and chronic pain conditions through their interactions with nociceptive neurons (nociceptors) in the peripheral nervous system (dorsal root ganglion and trigeminal ganglion neurons) or the central nervous system (spinal cord nociceptors).
  • On a molecular level, we investigate how different non-neuronal cell types contribute to pain conditions, through their production of painful (pro-nociceptive) or pain-relieving (anti-nociceptive) signaling molecules. These include conventional immune pathways, such as cytokines, chemokines, and toll-like receptors (TLRs), as well as unconventional neuromodulators, such as secreted miRNAs [PMID: 24698267]

Pain and itch regulation by non-neuronal cells and inflammation

  • We also study the distinct cellular and molecular mechanisms responsible for acute and chronic itch [PMID: 21037581, 30033153].

Resolution mechanisms and mediators of pain [PMID: 20383154, PMID: 21963090]

One of the key mechanisms for the transition from acute pain to chronic pain is a failure in the resolution of acute pain and acute inflammation.

  • We investigate how specialized pro-resolution mediators (SPMs), such as resolvins, neuroprotectins, and marresins, derived from omega-3 unsaturated fatty acids DHA and EPA, control pain by regulating inflammation, glial activation, TRP channels, and synaptic plasticity [PMID: 22171045].

Immune checkpoint inhibitors in the nervous system [PMID 28530662]

We examine how PD-L1 and PD-1 regulate neuronal activity in the PNS and CNS.

Development of Novel Pain Therapeutics and Diagnosis for the Translation from Bench to Bed

    • Specialized Proresolving Mediators (SPMs) [PMID: 30010619]: We investigate how SPMs, such as neuroprotectin D1 (NPD1) alleviate pain via specific receptors (e.g., GPR37) and distinct mechanisms (phagocytosis).
    • Stem cells [PMID: 26168219]: We are testing new methods that can enhance the homing and analgesic efficacy of bone marrow stem cells.
    • Immune therapy and cancer pain [PMID 28530662]: We examine how PD-L1 and PD-1 regulate neuronal activity and cancer pain.
    • Neuromodulation: We investigate how neuromodulation such as electroacupuncture and auricular stimulation can produce long-term pain relief via regulation of neuro- inflammation.
    • Human sensory neurons [PMID: 28424991, 27916453, 26479925]: We use human DRG neurons from donors to test mechanisms and treatments of clinical pain in “a dish”.
Amanda Andriessen

Amanda Andriessen
Undergraduate Student

Sangsu Bang, PhD

Sangsu Bang, PhD
Postdoctoral Fellow

Christopher Donnelly, DDS, PhD

Christopher Donnelly, DDS, PhD
Postdoctoral Fellow

Yul Huh

Yul Huh
PhD Student

Ru-Rong Ji, PhD

Ru-Rong Ji, PhD
Laboratory Director

Junli Zhao, PhD

Junli Zhao, PhD
Postdoctoral Fellow

Ouyang Chen
PhD Student

Kenta Furutani, MD, PhD
Research Fellow

Wei He, PhD
Research Fellow

Michael Lee
Undergraduate Student

Yutaka Matsuoka, MD, PhD
Research Fellow

Sreya Rahman
Undergraduate Student

Alexus Roberts
Undergraduate Student

Yuqing Wang, PhD
Research Fellow

Shirley Morton
Staff Assistant

Selected Recent Publications at Duke (Since 2012)

  1. Wang Z, Jiang C, He Q, Matsuda M, Han Q, Wang K, Bang S, Ding H, Ko MC, Ji RR. Anti-PD-1 treatment impairs opioid antinociception in rodents and nonhuman primates. Sci Transl Med. 2020 Feb 19;12(531).
  2. Suo Y, Wang Z, Zubcevic L, Hsu AL, He Q, Borgnia MJ, Ji RR, Lee SK. Structural insights into electrophile irritant sensing by the human TRPA1 channel. Neuron, 2019, 2020 Mar 4;105(5):882-894.
  3. Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat Rev Neurosci. 2019 Nov;20(11):667-685.
  4. Lopez T, Mustafa Z, Chen C, Lee KB, Ramirez A, Benitez C, Luo X, Ji RR, Ge X. Functional selection of protease inhibitory antibodies. Proc Natl Acad Sci U S A. 2019 Aug 13;116(33): 16314-16319.
  5. Luo X, Huh Y, Bang S, He Q, Zhang L, Matsuda M, Ji RR. Macrophage Toll-like receptor 9 contributes to chemotherapy-induced neuropathic pain in male mice. J Neurosci. 2019 Aug 28;39(35):6848-6864.
  6. Chamessian A, Matsuda M, Young M, Wang M, Zhang ZJ, Liu D, Tobin B, Xu ZZ, Van de Ven T, Ji RR. Is Optogenetic activation of Vglut1-positive Aβ low-threshold mechanoreceptors sufficient to induce tactile allodynia in mice after nerve injury? J Neurosci. 2019 Jul 31;39(31):6202-6215.
  7. Han Q, Liu D, Convertino M, Wang Z, Jiang C, Kim YH, Luo X, Zhang X, Nackley A, Dokholyan NV, Ji RR. miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus. Neuron. 2018 Aug 8;99(3):449-463.e6.
  8. Bang S, Xie YK, Zhang ZJ, Wang Z, Xu ZZ, Ji RR. GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain. J Clin Invest. 2018 Aug 1;128(8):3568-3582.
  9. Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain. Anesthesiology. 2018 Aug;129(2):343-366.
  10. Stogsdill JA, Ramirez J, Liu D, Kim YH, Baldwin KT, Enustun E, Ejikeme T, Ji RR, Eroglu C. Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis. Nature. 2017 Nov 8;551(7679):192-197.
  11. Chen G, Kim YH, Li H, Luo H, Liu DL, Zhang ZJ, Lay M, Chang W, Zhang YQ, Ji RR. PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1. Nat Neurosci. 2017 Jul;20(7):917-926.
  12. Han Q, Kim YH, Wang X, Liu D, Zhang ZJ, Bey AL, Lay M, Chang W, Berta T, Zhang Y, Jiang YH, Ji RR. SHANK3 deficiency impairs heat hyperalgesia and TRPV1 signaling in primary sensory neurons. Neuron, Dec 21;92(6):1279-1293, 2016
  13. Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science, 2016, Nov 4; 354(6312):572-577.
  14. Chen G, Xie RG, Gao YJ, Xu ZZ, Zhao LX, Bang S, Berta T, Park CK, Lay M, Chen W, Ji RR. β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain. Nat Commun. 2016 Aug 19;7:12531. doi: 10.1038/ncomms12531.
  15. Jiang BC, Cao DL, Zhang X, Zhang ZJ, He LN, Li CH, Zhang WW, Wu XB, Berta T, Ji RR, Gao YJ. CXCL13 drives spinal astrocyte activation and neuropathic pain via CXCR5. J Clin Invest. 2016 Feb;126(2):745-61.
  16. Singh SK, Stogsdill JA, Pulimood NS, Dingsdale H, Kim YH, Pilaz LJ, Kim IH, Manhaes AC, Rodrigues WS Jr, Pamukcu A, Enustun E, Ertuz Z, Scheiffele P, Soderling SH, Silver DL, Ji RR, Medina AE, Eroglu C. Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin. Cell 2016 Jan 14;164(1-2):183-96.
  17. Xu ZZ, Kim YH, Bang S, Zhang Y, Berta T, Wang F, Oh SB, Ji RR. Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade. Nature Medicine. 2015 21(11):1326-3.
  18. Taves S, Berta T, Liu DL, Gan S, Chen G, Kim YH, Van de Ven T, Laufer S, Ji RR. Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: Sex-dependent microglial signaling in the spinal cord. Brain Behav Immun. 2015 Oct 19. pii: S0889-1591(15)30032-5.
  19. Chen G, Park CK, Xie RG, Ji RR. Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-b secretion. J Clin Invest. 2015;125(8):3226-40.
  20. Sorge RE, Mapplebeck JCS, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin JS, Sotocinal SG, Chen D,  Yang M, Shi XQ, Huang H, Pillon NJ, Bilan PJ, Tu Y, Klip A, Ji RR, Zhang J, Michael W Salter MS,  Mogil JS. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. 2015, Nat Neurosci, 2015 Aug;18(8):1081-3.
  21. Ji RR, Xu ZZ, Gao YJ. Neuroinflammation drives chronic pain: emerging targets with pro- and anti-inflammatory roles. Nature Reviews Drug Discovery, 2014, 13:533-548.
  22. Chen G, Park CK, Xie RG, Nedergaard M, Ji RR (2014) Connexin-43 induces chemokine release from spinal cord astrocytes to maintain late-phase neuropathic pain in mice. Brain, 2014, 137:2193-2209.
  23. Park CK, Xu ZZ, Berta, T, Han QJ, Liu XJ, Ji RR (2014)  Extracellular miRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron, 82:47-54.
  24. Berta T, Park CK, Xie RG, Xu ZZ, Lu N, Ji RR (2014)  Extracellular caspase-6 drives murine inflammatory pain via microglia TNF-a secretion. J Clin Invest. 2014; 124:1173-86.
  25. Ji RR, Berta T, and Nedergaard M. Glia and pain: Is chronic pain and gliopathy? Pain, 2013, 154 Suppl 1: S10-28.
  26. Lu Y, Dong H, Gao Y, Gong Y, Ren Y, Gu N, Zhou S, Xia N, Sun YY, Ji RR, Xiong L. A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia. J Clin Invest. 2013, 123:4050-62.
  27. Liu T, Berta T, Xu ZZ, Park CK, Zhang L, Lü N, Liu Q, Liu Y, Gao YJ, Liu YC, Ma Q, Dong X, Ji RR. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest. 2012, 122:2195-2207.

Ru-Rong Ji, PhD

Ru-Rong Ji, PhD

Distinguished Professor of Anesthesiology, School of Medicine
Professor in Neurobiology
Professor in Cell Biology
Chief, Pain Research
Director, Center for Translational Pain Medicine

Visit the Duke Pain Program:
Basic, Translational, and Clinical Pain Research

Lab Opportunities

The Ji lab is always recruiting talented postdoctoral fellows, visiting scholars, graduate students, and undergraduate students. Interested candidates should email their CV, a brief statement of interests, and a list of three references to Dr. Ru-Rong Ji.

Contact Us

Duke University Medical Center
DUMC Box 3094
Office: 919-684-9387
Fax: 919-684-2411

Chris KeithSensory Plasticity and Pain Research Laboratory