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.
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.
Major Research Interests
Pain 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]
- 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”.
In the News
December 23, 2021
December 17, 2021
November 23, 2021
November 12, 2021
October 27, 2021
June 23, 2021
February 1, 2021
November 19, 2020
July 21, 2020
June 5, 2020
May 11, 2020
Congratulations to Dr. Christopher Donnelly on Earning First Place in Two Award Competitions for His Research Project in Which He Identified a New Role for a Protein, Called STING, in the Regulation of Pain.
November 19, 2019
Global List of Highly Cited Puts Duke in Top Ten
December 3, 2018
Anesthesiologist Named a Highly Cited Researcher for 2018
January 4, 2017
Autism Gene Modulates Thermal Pain - Pain Research Forum
November 14, 2016
Dr. Ji Published in Special Issue of Science - Duke Anesthesiology
December 1, 2015
Pain: TLR5 opens the door to neuropathic-pain treatment. - NCBI
Sharat Chandra, PhD
Kenta Furutani, MD, PhD
Ran Guo, MD, PhD
Wei He, PhD
Yutaka Matsuoka, MD, PhD
Yuqing Wang, PhD
Jing Xu, PhD
Selected Recent Publications at Duke (Since 2012)
- Luo X, Chen O, Wang Z, Bang S, Ji J, Lee SH, Huh Y, Furutani K, He Q, Tao X, Ko MC, Bortsov A, Donnelly CR, Chen Y, Nackley A, Berta T, Ji RR. IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice. Neuron. 2021 Sep 1;109(17):2691-2706.e5.
- Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras X, Rülicke T, Hippenmeyer S, Estévez R, Ji RR, Eroglu C. HepaCAM controls astrocyte self-organization and coupling. Neuron. 2021 Aug 4;109(15):2427-2442.e10.
- Wang K, Donnelly CR, Jiang C, Liao Y, Luo X, Tao X, Bang S, McGinnis A, Lee M, Hilton MJ, Ji RR. STING suppresses bone cancer pain via immune and neuronal modulation. Nat Commun. 2021 Jul 27;12(1):4558.
- Donnelly CR, Jiang C, Andriessen AS, Wang K, Wang Z, Ding H, Zhao J, Luo X, Lee MS, Lei YL, Maixner W, Ko MC, Ji RR. STING controls nociception via type I interferon signalling in sensory neurons. Nature. 2021 Mar;591(7849):275-280.
- Wang Z, Jiang C, Yao H, Chen O, Rahman S, Gu Y, Zhao J, Huh Y, Ji RR. Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition. Brain. 2021 Mar 3;144(2):665-681.
- Deerhake ME, Danzaki K, Inoue M, Cardakli ED, Nonaka T, Aggarwal N, Barclay WE, Ji RR, Shinohara ML. Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M. Immunity. 2021 Mar 9;54(3):484-498.e8.
- Bang S, Donnelly CR, Luo X, Toro-Moreno M, Tao X, Wang Z, Chandra S, Bortsov AV, Derbyshire ER, Ji RR. Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice. Nat Commun. 2021 Mar 17;12(1):1704.
- Brigham NC, Ji RR, Becker ML. Degradable polymeric vehicles for postoperative pain management. Nat Commun. 2021 Mar 1;12(1):1367.
- 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).
- 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.
- Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat Rev Neurosci. 2019 Nov;20(11):667-685.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science, 2016, Nov 4; 354(6312):572-577.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Ji RR, Berta T, and Nedergaard M. Glia and pain: Is chronic pain and gliopathy? Pain, 2013, 154 Suppl 1: S10-28.
- 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.
- 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.