STING/NF-κB/IL-6-Mediated Inflammation in Microglia Contributes to Spared Nerve Injury (SNI)-Induced Pain Initiation

Abdullah A, Zhang M, Frugier T, Bedoui S, Taylor JM, Crack PJ (2018) STING-mediated type-I interferons contribute to the neuroinflammatory process and detrimental effects following traumatic brain injury. J Neuroinflammation 15:323 Ahn J, Gutman D, Saijo S, Barber GN (2012) STING manifests self DNA-dependent inflammatory disease. Proceedings of the National Academy of Sciences of the United States of America Baral P, Udit S, Chiu IM (2019) Pain and immunity: implications for host defence. Nat Rev Immunol Barker RN, Erwig LP, Pearce WP, Devine A, Rees AJ (1999) Differential Effects of Necrotic or Apoptotic Cell Uptake on Antigen Presentation by Macrophages. Pathobiology 67:302–305 Barragan-Iglesias P, Franco-Enzastiga U, Jeevakumar V, Shiers S, Wangzhou A, Granados-Soto V, Campbell ZT, Dussor G, Price TJ (2020) Type I Interferons Act Directly on Nociceptors to Produce Pain Sensitization: Implications for Viral Infection-Induced Pain. J Neurosci 40:3517–3532 Bauer S (2006) Toll-erating self DNA. Nat Immunol 7:13–15 Beutler B (2009) Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases. Immunol Rev 227 Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69 Burdette DL, Vance RE (2013) STING and the innate immune response to nucleic acids in the cytosol. Nat Immunol 14:19–26 Cao F, Gao F, Xu AJ, Chen ZJ, Chen SS, Yang H, Yu HH, Mei W, Liu XJ, Xiao XP et al (2010) Regulation of spinal neuroimmune responses by prolonged morphine treatment in a rat model of cancer induced bone pain. Brain Res 1326:162–173 Chamilos G, Gregorio J, Meller S, Lande R, Kontoyiannis DP, Modlin RL, Gilliet M (2012) Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood 120:3699 Chang HH, Miaw SC, Tseng W, Sun YW, Liu CC, Tsao HW, Ho IC (2013) PTPN22 Modulates Macrophage Polarization and Susceptibility to Dextran Sulfate Sodium-Induced Colitis. J Immunol Chen G, Zhang YQ, Qadri YJ, Serhan CN, Ji RR (2018a) Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain. Neuron 100:1292–1311 Chen Q, Sun L, Chen ZJ (2016) Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat Immunol 17:1142–1149 Chen SP, Sun J, Zhou YQ, Cao F, Braun C, Luo F, Ye DW, Tian YK (2018b) Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models. Mol Pain 14:1744806918793232 Decosterd I, Woolf CJ (2000) Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 87:149–158 Deleo JA, Colburn RW, Nichols M, Malhotra A (1996) Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. Journal of Interferon & Cytokine Research the Official Journal of the International Society for Interferon & Cytokine Research 16:695–700 Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, Li XD, Mauceri H, Beckett M, Darga T et al (2014) STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors. Immunity 41:843–852 Dominguez E, Mauborgne A, Mallet J, Desclaux M, Pohl M (2010) SOCS3-mediated blockade of JAK/STAT3 signaling pathway reveals its major contribution to spinal cord neuroinflammation and mechanical allodynia after peripheral nerve injury. J Neurosci Dominguez E, Rivat C, Pommier B, Mauborgne A, Pohl M (2008) JAK/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat. J Neurochem 107:50–60 Donnelly CR, Jiang C, Andriessen AS, Wang K, Wang Z, Ding H, Zhao J, Luo X, Lee MS, Lei YL et al (2021) STING controls nociception via type I interferon signalling in sensory neurons. Nature Dunphy G, Flannery SM, Almine JF, Connolly DJ, Paulus C, Jonsson KL, Jakobsen MR, Nevels MM, Bowie AG, Unterholzner L (2018) Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-kappaB Signaling after Nuclear DNA Damage. Mol Cell 71:745–760 e745 Fairbanks CA (2003) Spinal delivery of analgesics in experimental models of pain and analgesia. Adv Drug Deliv Rev 55:1007–1041 Grace PM, Rolan PE, Hutchinson MR (2011) Peripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain. Brain Behav Immun 25:1322–1332 Haag SM, Gulen MF, Reymond L, Gibelin A, Abrami L, Decout A, Heymann M, van der Goot FG, Turcatti G, Behrendt R, Ablasser A (2018) Targeting STING with covalent small-molecule inhibitors. Nature 559:269–273 Hilkens CM, Schlaak JF, Kerr IM (2003) Differential responses to IFN-alpha subtypes in human T cells and dendritic cells. J Immunol 171:5255–5263 Hou Y, Liang H, Rao E, Zheng W, Huang X, Deng L, Zhang Y, Yu X, Xu M, Mauceri H et al (2018) Non-canonical NF-kappaB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy. Immunity 49:490–503 e494 Hornung V, Latz E (2010) Intracellular DNA recognition. Nat Rev Immunol 10:123–130 Hunter MM, Wang A, Parhar KS, Johnston MJG, Rooijen NV, Beck PL, Mckay DM (2010) In Vitro-Derived Alternatively Activated Macrophages Reduce Colonic Inflammation in Mice. Gastroenterology 138:1395–1405 Inoue K, Tsuda M (2018) Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci 19:138–152 Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, Treede RD (2011) A new definition of neuropathic pain. Pain 152:2204–2205 Jiang X, Liu G, Hu Z, Chen G, Chen J, Lv Z (2019) cGAMP inhibits tumor growth in colorectal cancer metastasis through the STING/STAT3 axis in a zebrafish xenograft model. Fish Shellfish Immunol 95:220–226 Kawai T, Akira S (2009) The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol Kawasaki Y, Zhang L, Cheng JK, Ji RR (2008) Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 28:5189–5194 Kim D, You B, Jo EK, Han SK, Simon MI, Lee SJ (2010) NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain. Proc Natl Acad Sci U S A 107:14851–14856 Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K, Hirakawa A, Takeuchi H, Suzumura A, Ishiguro N, Kadomatsu K (2013) Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis 4:e525 Larner AC, Chaudhuri A, Darnell JE Jr (1986) Transcriptional induction by interferon. New protein (s) determine the extent and length of the induction. J Biol Chem 261:453–459 Le WD, Rowe D, Xie WJ, Ortiz I, Appel SH (2001) Microglial Activation and Dopaminergic Cell Injury: An In Vitro Model Relevant to Parkinson’s Disease. The Journal of Neuroence: the Official Journal of the Society for Neuroence 21:8447–8455 Li N, Zhou H, Wu H, Wu Q, Duan M, Deng W, Tang Q (2019) STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol 24:101215 Li T, Chen ZJ (2018) The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer. J Exp Med 215:1287–1299 Li T, Liu T, Chen X, Li L, Feng M, Zhang Y, Wan L, Zhang C, Yao W (2020) Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain. J Neuroinflammation 17:211 Liu S, Karaganis S, Mo RF, Li XX, Wen RX, Song XJ (2020) IFNbeta Treatment Inhibits Nerve Injury-induced Mechanical Allodynia and MAPK Signaling By Activating ISG15 in Mouse Spinal Cord. J Pain 21:836–847 Luo W, Wang Y, Zhang L, Ren P, Shen YH (2020) Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture. Circulation 141:42–66 Mathur V, Burai R, Vest RT, Bonanno LN, Lehallier B, Zardeneta ME, Mistry KN, Do D, Marsh SE, Abud EM et al (2017) Activation of the STING-Dependent Type I Interferon Response Reduces Microglial Reactivity and Neuroinflammation. Neuron 96:1290–1302 e1296 Mc A, Jmd A, Ddlba B (2012) The role of the immune system in the generation of neuropathic pain - ScienceDirect. Lancet Neurol 11:629–642 Möser C, Kynast K, Baatz K, Russe OQ, Niederberger E (2011) The Protein Kinase IKKε Is a Potential Target for the Treatment of Inflammatory Hyperalgesia. J Immunol 187:2617 Moser CV, Stephan H, Altenrath K, Kynast KL, Russe OQ, Olbrich K, Geisslinger G, Niederberger E (2015) TANK-binding kinase 1 (TBK1) modulates inflammatory hyperalgesia by regulating MAP kinases and NF-kappaB dependent genes. J Neuroinflammation 12:100 Nicholson SE, Hilton DJ (1998) The SOCS proteins: a new family of negative regulators of signal transduction. J Leukoc Biol 63:665–668 Palm NW, Medzhitov R (2009) Pattern recognition receptors and control of adaptive immunity. Immunol Rev 227:221–233 Patrushev M, Kasymov V, Patrusheva V, Ushakova T, Gogvadze V, Gaziev A (2004) Mitochondrial permeability transition triggers the release of mtDNA fragments. Cellular & Molecular Life Sciences Cmls 61:3100–3103 Peng J, Gu N, Zhou L, Eyo UB, Murugan M, Gan WB, Wu LJ (2016) Microglia and monocytes synergistically promote the transition from acute to chronic pain after nerve injury. Nat Commun 7:12029 Peng Y, Zhuang J, Ying G, Zeng H, Zhou H, Cao Y, Chen H, Xu C, Fu X, Xu H et al (2020) Stimulator of IFN genes mediates neuroinflammatory injury by suppressing AMPK signal in experimental subarachnoid hemorrhage. J Neuroinflammation 17:165 Pinho-Ribeiro FA, Verri WA, Chiu IM (2016) Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation. Trends Immunol 5 Robinson SM, Mann DA (2010) Role of nuclear factor κB in liver health and disease. Clin Sci 118:691–705 Saitoh T, Fujita N, Hayashi T, Takahara K, Satoh T, Lee H, Matsunaga K, Kageyama S, Omori H, Noda T et al (2009) Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci U S A 106:20842–20846 Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N (2000) Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191:423–434 Sliter DA, Martinez J, Hao L, Chen X, Sun N, Fischer TD, Burman JL, Li Y, Zhang Z, Narendra DP et al (2018) Parkin and PINK1 mitigate STING-induced inflammation. Nature 561:258–262 Sommer C, Leinders M, Uceyler N (2018) Inflammation in the pathophysiology of neuropathic pain. Pain 159:595–602 Sorge RE, Mapplebeck J, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin JS, Sotocinal SG, Chen D (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081–1083 Van Steenwinckel J, Reaux-Le Goazigo A, Pommier B, Mauborgne A, Dansereau MA, Kitabgi P, Sarret P, Pohl M, Melik Parsadaniantz S (2011) CCL2 released from neuronal synaptic vesicles in the spinal cord is a major mediator of local inflammation and pain after peripheral nerve injury. J Neurosci 31:5865–5875 Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24:450–455 West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA et al (2015) Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520:553–557 West AP, Shadel GS (2017) Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol White MJ, McArthur K, Metcalf D, Lane RM, Cambier JC, Herold MJ, van Delft MF, Bedoui S, Lessene G, Ritchie ME et al (2014) Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production. Cell 159:1549–1562 Woller SA, Ocheltree C, Wong SY, Bui A, Fujita Y, Dos Santos GG, Yaksh TL, Corr M (2019) Neuraxial TNF and IFN-beta co-modulate persistent allodynia in arthritic mice. Brain Behav Immun 76:151–158 Xu N, Tang XH, Pan W, Xie ZM, Zhang GF, Ji MH, Yang JJ, Zhou MT, Zhou ZQ (2017) Spared Nerve Injury Increases the Expression of Microglia M1 Markers in the Prefrontal Cortex of Rats and Provokes Depression-Like Behaviors. Front Neurosci 11:209 Zhang CX, Ye SB, Ni JJ, Cai TT, Liu YN, Huang DJ, Mai HQ, Chen QY, He J, Zhang XS et al (2019) STING signaling remodels the tumor microenvironment by antagonizing myeloid-derived suppressor cell expansion. Cell Death Differ 26:2314–2328 Zhao Q, Wei Y, Pandol SJ, Li L, Habtezion A (2018) STING Signaling Promotes Inflammation in Experimental AcutePancreatitis. Gastroenterology 1822–1835 Zhou YQ, Liu DQ, Chen SP, Chen N, Sun J, Wang XM, Cao F, Tian YK, Ye DW (2020) Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain. Acta Pharmacol Sin Zhou YQ, Liu DQ, Chen SP, Sun J, Zhou XR, Rittner H, Mei W, Tian YK, Zhang HX, Chen F, Ye DW (2018) Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain. Redox Biol 14:391–397 Zhou YQ, Liu Z, Liu ZH, Chen SP, Li M, Shahveranov A, Ye DW, Tian YK (2016) Interleukin-6: an emerging regulator of pathological pain. J Neuroinflammation 13:141 Zhu Q, Man SM, Gurung P, Liu Z, Vogel P, Lamkanfi M, Kanneganti TD (2014) Cutting edge: STING mediates protection against colorectal tumorigenesis by governing the magnitude of intestinal inflammation. J Immunol 193:4779–4782 Zhu Y, An X, Zhang X, Qiao Y, Zheng T, Li X (2019) STING: a master regulator in the cancer-immunity cycle. Mol Cancer 18:152