Selective activation of microglia facilitates synaptic strength
Open accessAbstract
Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1β from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Activation of the fractalkine receptor (CX3CR1) in microglial cells increases synaptic strength; deficiency in this receptor results in reduced hippocampal synaptic plasticity.
“The activation of the fractalkine receptor (CX3CR1) in microglial cells, increases synaptic strength. However, deficiency in this receptor results in a reduced hippocampal synaptic plasticity (Rogers et al., 2011; Clark et al., 2015).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Clark et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566 · see citing works
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023 · see citing works
AChE-stained horizontal sections of the rat brain in stereotaxic coordinates
Paxinos, G., WATSON, C. R. R., & Emson, P. C. (1980) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(80)90021-7 · Cited by 4,501 · see citing works
Malenka, R. C., & Bear, M. F. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.012 · Cited by 3,968 · see citing works
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · see citing works
BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain
Coull, J. A. M., Beggs, S., Boudreau, D., Boivin, D., Tsuda, M., Inoue, K., Gravel, C., Salter, M. W., & De Koninck, Y. (2005) · Nature · doi:10.1038/nature04223 · Cited by 1,965 · see citing works
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · see citing works
Samad, T. A., Moore, K. A., Sapirstein, A., Billet, S. E., Allchorne, A. J., Poole, S., Bonventre, J. V., & Woolf, C. J. (2001) · Nature · doi:10.1038/35068566 · Cited by 1,282 · see citing works
Glia and pain: Is chronic pain a gliopathy?
Ji, R., Berta, T., & Nedergaard, M. (2013) · Pain · doi:10.1016/j.pain.2013.06.022 · Cited by 1,193 · see citing works
Kawasaki, Y., Zhang, L., Cheng, J.-K., & Ji, R.-R. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3338-07.2008 · Cited by 1,162 · see citing works
Models and Mechanisms of Hyperalgesia and Allodynia
Sandkühler, J. (2009) · Physiological Reviews · doi:10.1152/physrev.00025.2008 · Cited by 1,148 · see citing works
Self-citationPostsynaptic signaling and plasticity mechanisms
Sheng, M., & Kim, M. J. (2002) · Science · doi:10.1126/science.1075333 · Cited by 731 · see citing works
Malmberg, A. B., & Yaksh, T. L. (1992) · Science · doi:10.1126/science.1381521 · Cited by 704 · see citing works
Williams, J. H. H., Errington, M. L., Lynch, M. A., & Bliss, T. V. P. (1989) · Nature · doi:10.1038/341739a0 · Cited by 627 · see citing works
NMDA receptors activate the arachidonic acid cascade system in striatal neurons
Dumuis, A., Sebben, M., Haynes, L., Pin, J., & Bockaert, J. (1988) · Nature · doi:10.1038/336068a0 · Cited by 593 · see citing works
Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity
Xanthos, D. N., & Sandkühler, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3617 · Cited by 580 · see citing works
Self-citationSynaptic Plasticity in Spinal Lamina I Projection Neurons That Mediate Hyperalgesia
Ikeda, H., Heinke, B., Ruscheweyh, R., & Sandkühler, J. (2003) · Science · doi:10.1126/science.1080659 · Cited by 569 · see citing works
Self-citationGlutamate-Dependent Neuroglial Calcium Signaling Differs Between Young and Adult Brain
Sun, W., McConnell, E., Paré, J., Xu, Q., Chen, M. J., Peng, W., Lovatt, D., Han, X., Smith, Y., & Nedergaard, M. (2013) · Science · doi:10.1126/science.1226740 · Cited by 512 · see citing works
Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain
Clark, A. K., Yip, P. K., Grist, J., Gentry, C., Staniland, A. A., Marchand, F., Dehvari, M., Wotherspoon, G., Winter, J., Ullah, J., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610811104 · Cited by 491 · see citing works
Self-citationSynaptic Amplifier of Inflammatory Pain in the Spinal Dorsal Horn
Ikeda, H., Stark, J., Fischer, H., Wagner, M. W., Drdla-Schutting, R., Jäger, T., & Sandkühler, J. (2006) · Science · doi:10.1126/science.1127233 · Cited by 451 · see citing works
Self-citationHippocampal Short- and Long-Term Plasticity Are Not Modulated by Astrocyte Ca 2+ Signaling
Agulhon, C., Fiacco, T. A., & McCarthy, K. D. (2010) · Science · doi:10.1126/science.1184821 · Cited by 409 · see citing works
Svensson, C. I., Maršala, M., Westerlund, A., Calcutt, N. A., Campana, W. M., Freshwater, J. D., Catalano, R., Feng, Y. J., Protter, A. A., Scott, B. T., et al. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01969.x · Cited by 385 · see citing works
Two Coincidence Detectors for Spike Timing-Dependent Plasticity in Somatosensory Cortex
Bender, V. A., Bender, K. J., Brasier, D. J., & Feldman, D. E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0176-06.2006 · Cited by 373 · see citing works
Zhuang, Z.-Y., Kawasaki, Y., Tan, P.-H., Wen, Y.-R., Huang, J., & Ji, R.-R. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.11.003 · Cited by 371 · see citing works
The Spinal Phospholipase-Cyclooxygenase-Prostanoid Cascade in Nociceptive Processing
Svensson, C. I., & Yaksh, T. L. (2002) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.42.092401.143905 · Cited by 302 · see citing works
Visualizing unstained neurons in living brain slices by infrared DIC-videomicroscopy
Dodt, H., & Zieglgänsberger, W. (1990) · Brain Research · doi:10.1016/0006-8993(90)90380-t · Cited by 291 · see citing works
Clark, A. K., Staniland, A. A., Marchand, F., Kaan, T. K. Y., McMahon, S. B., & Malcangio, M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3295-09.2010 · Cited by 291 · cited 2× · see citing works
“Quantitative assessment of immunostaining in spinal cord sections was performed by counting the number of positive profiles within a fixed area of the dorsal horn (Clark et al., 2006, 2010, 2012).”
MethodSelf-citationMilligan, E. D., Zapata, V., Chacur, M., Schoeniger, D., Biedenkapp, J. C., O’Connor, K., Verge, G. M., Chapman, G. A., Green, P., Foster, A. C., et al. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03709.x · Cited by 289 · see citing works
Presynaptic induction of heterosynaptic associative plasticity in the mammalian brain
Humeau, Y., Shaban, H., Bissière, S., & Lüthi, A. (2003) · Nature · doi:10.1038/nature02194 · Cited by 253 · see citing works
Malenka, R. C., Lancaster, B., & Zucker, R. S. (1992) · Neuron · doi:10.1016/0896-6273(92)90227-5 · Cited by 250 · see citing works
Park, C.-K., Lü, N., Xu, Z.-Z., Liu, T., Serhan, C. N., & Ji, R.-R. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2443-11.2011 · Cited by 241 · see citing works
Glia: The many ways to modulate synaptic plasticity
Achour, S. B., & Pascual, O. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.02.013 · Cited by 240 · see citing works
The Liberation of Fractalkine in the Dorsal Horn Requires Microglial Cathepsin S
Clark, A. K., Yip, P. K., & Malcangio, M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0828-09.2009 · Cited by 219 · see citing works
Self-citationInduction of Synaptic Long-Term Potentiation After Opioid Withdrawal
Drdla-Schutting, R., Gassner, M., Gingl, E., & Sandkühler, J. (2009) · Science · doi:10.1126/science.1171759 · Cited by 216 · see citing works
Self-citationGruber-Schoffnegger, D., Drdla-Schutting, R., Hönigsperger, C., Wunderbaldinger, G., Gassner, M., & Sandkühler, J. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5087-12.2013 · Cited by 207 · see citing works
Self-citationExtracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion
Berta, T., Park, C., Xu, Z., Xie, R.-G., Liu, T., Lü, N., Liu, Y., & Ji, R. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72230 · Cited by 195 · see citing works
Sang, N., Zhang, J., Marcheselli, V., Bazan, N. G., & Chen, C. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2392-05.2005 · Cited by 191 · see citing works
Milligan, E. D., Zapata, V., Schoeniger, D., Chacur, M., Green, P., Poole, S., Martin, D., Maier, S. F., & Watkins, L. R. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04470.x · Cited by 178 · see citing works
Staniland, A. A., Clark, A. K., Wodarski, R., Sasso, O., Μaione, F., D’Acquisto, F., & Malcangio, M. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06837.x · Cited by 168 · see citing works
Self-citationFractalkine/CX3CR1 signaling during neuropathic pain
Clark, A. K., & Malcangio, M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00121 · Cited by 161 · see citing works
Self-citationSanfeliu, C., Hunt, A., & Patel, A. J. (1990) · Brain Research · doi:10.1016/0006-8993(90)91228-9 · Cited by 154 · see citing works
Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity
Limatola, C., Lauro, C., Catalano, M., Ciotti, M. T., Bertollini, C., Di Angelantonio, S., Ragozzino, D., & Eusebi, F. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.03.023 · Cited by 153 · see citing works
A novel role of phospholipase A2 in mediating spinal cord secondary injury
Liu, N., Zhang, Y. P., Titsworth, W. L., Jiang, X., Han, S., Lu, P., Shields, C. B., & Xu, X. (2006) · Annals of Neurology · doi:10.1002/ana.20798 · Cited by 153 · see citing works
Microglial signalling mechanisms: Cathepsin S and Fractalkine
Clark, A. K., & Malcangio, M. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.09.012 · Cited by 149 · see citing works
Self-citationRagozzino, D., Angelantonio, S. D., Trettel, F., Bertollini, C., Maggi, L., Gross, C. T., Charo, I. F., Limatola, C., & Eusebi, F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3192-06.2006 · Cited by 129 · see citing works
Rapid co‐release of interleukin 1β and caspase 1 in spinal cord inflammation
Clark, A. K., D'Aquisto, F., Gentry, C., Marchand, F., McMahon, S. B., & Malcangio, M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04126.x · Cited by 108 · see citing works
Self-citationErasure of a Spinal Memory Trace of Pain by a Brief, High-Dose Opioid Administration
Drdla-Schutting, R., Benrath, J., Wunderbaldinger, G., & Sandkühler, J. (2012) · Science · doi:10.1126/science.1211726 · Cited by 106 · see citing works
Self-citationLuo, C., Gangadharan, V., Bali, K. K., Xie, R., Agarwal, N., Kurejová, M., Tappe‐Theodor, A., Tegeder, I., Feil, S. C., Lewin, G. R., et al. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001283 · Cited by 100 · see citing works
Gühring, H., Görig, M., Ateş, M., Coste, O., Zeilhofer, H. U., Pahl, A. M., Rehse, K., & Brune, K. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-17-06714.2000 · Cited by 99 · see citing works
Zhong, Y., Zhou, L.-J., Ren, W.-J., Xin, W.-J., Li, Y.-Y., Zhang, T., & Liu, X.-G. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.01.007 · Cited by 97 · cited 3× · see citing works
“Indeed, glia cell contribution to synaptic transmission differs greatly between the brain and spinal cord (Ben Achour and Pascual, 2010; Zhong et al., 2010; GruberSchoffnegger et al., 2013).”
BackgroundClark, A. K., Grist, J., Al‐Kashi, A., Perretti, M., & Malcangio, M. (2011) · Arthritis & Rheumatism · doi:10.1002/art.34351 · Cited by 88 · see citing works
Self-citationFractalkine/CX3CR1 Signalling in Chronic Pain and Inflammation
Clark, A. K., Staniland, A. A., & Malcangio, M. (2011) · Current Pharmaceutical Biotechnology · doi:10.2174/138920111798357465 · Cited by 87 · see citing works
Self-citationMaggi, L., Trettel, F., Scianni, M., Bertollini, C., Eusebi, F., Fredholm, B. B., & Limatola, C. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.07.016 · Cited by 84 · see citing works
Minami, T., Okuda‐Ashitaka, E., Hori, Y., Sakuma, S., Sugimoto, T., Sakimura, K., Mishina, M., & Ito, S. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00602.x · Cited by 82 · see citing works
Spinal phospholipase A2 in inflammatory hyperalgesia: role of Group IVA cPLA2
Lucas, K. K., Svensson, C. I., Hua, X., Yaksh, T. L., & Dennis, E. A. (2005) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706116 · Cited by 79 · see citing works
Liu, T., Jiang, C., Fujita, T., Luo, S., & Kumamoto, E. (2013) · Molecular Pain · doi:10.1186/1744-8069-9-16 · Cited by 74 · see citing works
Scianni, M., Antonilli, L., Chece, G., Cristalli, G., Castro, M. A. D., Limatola, C., & Maggi, L. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-108 · Cited by 66 · see citing works
Minami, T., Nishihara, I., Ito, S., Sakamoto, K., Hyodo, M., & Hayaishi, O. (1995) · Pain · doi:10.1016/0304-3959(94)00183-f · Cited by 55 · see citing works
Dauch, J. R., Yanik, B. M., Hsieh, W., Oh, S. S., & Cheng, H. T. (2012) · Glia · doi:10.1002/glia.22349 · Cited by 46 · see citing works
Non-Hebbian plasticity at C-fiber synapses in rat spinal cord lamina I neurons
Naka, A., Gruber-Schoffnegger, D., & Sandkühler, J. (2013) · Pain · doi:10.1016/j.pain.2013.04.011 · Cited by 35 · see citing works
Self-citationImmunocytochemical localization of cPLA2 in rat and monkey spinal cord
Ong, W., Horrocks, L. A., & Farooqui, A. A. (1999) · Journal of Molecular Neuroscience · doi:10.1007/bf02736926 · Cited by 32 · see citing works
Constandil, L., Hernández, A., Pélissier, T., Arriagada, O., Espinoza, K., Burgos, H., & Laurido, C. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2756 · Cited by 26 · see citing works
Kim, D., Fitzsimmons, B., Hefferan, M. P., Svensson, C. I., Wancewicz, E. V., Monia, B. P., Hung, G., Butler, M., Maršala, M., Hua, X., et al. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.033 · Cited by 21 · see citing works
Taylor, A. L., Bonventre, J. V., Uliasz, T. F., Hewett, J. A., & Hewett, S. J. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05527.x · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuroinflammation and Central Sensitization in Chronic and Widespread Pain
Ji, R.-R., Nackley, A., Huh, Y., Terrando, N., & Maixner, W. (2018) · Anesthesiology · doi:10.1097/aln.0000000000002130 · Cited by 1,630 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
Pain regulation by non-neuronal cells and inflammation
Ji, R.-R., Chamessian, A., & Zhang, Y.-Q. (2016) · Science · doi:10.1126/science.aaf8924 · Cited by 1,314 · see citing works
Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential
Inoue, K., & Tsuda, M. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.2 · Cited by 908 · see citing works
Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain
Chen, G., Zhang, Y., Qadri, Y. J., Serhan, C. N., & Ji, R. (2018) · Neuron · doi:10.1016/j.neuron.2018.11.009 · Cited by 791 · see citing works
Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K., & Tremblay, M. (2017) · The Journal of Physiology · doi:10.1113/jp272134 · Cited by 562 · see citing works
The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma.
Ramirez, A. I., de Hoz, R., Salobrar-Garcia, E., Salazar, J. J., Rojas, B., Ajoy, D., López-Cuenca, I., Rojas, P., Triviño, A., & Ramírez, J. M. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00214 · Cited by 466 · see citing works
Microglia in CNS development: Shaping the brain for the future
Mosser, C., Baptista, S., Arnoux, I., & Audinat, É. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.002 · Cited by 289 · see citing works
Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions
Cserép, C., Pósfai, B., & Dénes, Á. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.007 · Cited by 256 · see citing works
Fractalkine receptor deficiency impairs microglial and neuronal responsiveness to chronic stress
Milior, G., Lecours, C., Samson, L., Bisht, K., Poggini, S., Pagani, F., Deflorio, C., Lauro, C., Alboni, S., Limatola, C., et al. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.024 · Cited by 247 · see citing works
Chemokines in chronic pain: cellular and molecular mechanisms and therapeutic potential
Jiang, B., Liu, T., & Gao, Y. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107581 · Cited by 236 · see citing works
Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission
Marinelli, S., Basilico, B., Marrone, M. C., & Ragozzino, D. (2019) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.05.017 · Cited by 233 · see citing works
Role of the immune system in neuropathic pain
Malcangio, M. (2019) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2019-0138 · Cited by 232 · see citing works
Self-citationMicroglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain
Zhou, L.-J., Peng, J., Xu, Y.-N., Zeng, W.-J., Zhang, J., Wei, X., Mai, C.-L., Lin, Z.-J., Liu, Y., Murugan, M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.087 · Cited by 228 · see citing works
Fumagalli, G., Monza, L., Cavaletti, G., Rigolio, R., & Meregalli, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.626687 · Cited by 183 · see citing works
Gliogenic LTP spreads widely in nociceptive pathways
Kronschläger, M. T., Drdla-Schutting, R., Gassner, M., Honsek, S. D., Teuchmann, H. L., & Sandkühler, J. (2016) · Science · doi:10.1126/science.aah5715 · Cited by 173 · see citing works
Self-citationNeuron–Microglia Interactions in Mental Health Disorders: “For Better, and For Worse”
Wohleb, E. S. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00544 · Cited by 164 · see citing works
A pharmacological basis of herbal medicines for epilepsy
Sucher, N. J., & Carles, M. (2015) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2015.05.012 · Cited by 157 · see citing works
Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain
Shim, H. S., Bae, C., Wang, J., Lee, K. H., Hankerd, K., Kim, H. K., Chung, J. M., & La, J. (2019) · Molecular Pain · doi:10.1177/1744806919840098 · Cited by 148 · see citing works
Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice
Yi, M., Liu, Y., Liu, K., Chen, T., Bosco, D. B., Zheng, J., Xie, M., Zhou, L., Qu, W., & Wu, L. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.11.030 · Cited by 142 · see citing works
Stress induced microglial activation contributes to depression
Li, B., Yang, W., Ge, T., Wang, Y., & Cui, R. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106145 · Cited by 149 · see citing works
Eyo, U. B., Peng, J., Murugan, M., Mo, M., Lalani, A., Xie, P., Xu, P., Margolis, D. J., & Wu, L. (2016) · eNeuro · doi:10.1523/eneuro.0209-16.2016 · Cited by 114 · see citing works
Shao, S., Xu, C.-B., Chen, C.-J., Shi, G.-N., Guo, Q.-L., Zhou, Y., Wei, Y.-Z., Wu, L., Shi, J.-G., & Zhang, T.-T. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02178-z · Cited by 112 · see citing works
Ion Channels and Receptors as Determinants of Microglial Function
Izquierdo, P., Attwell, D., & Madry, C. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2018.12.007 · Cited by 102 · see citing works
Boakye, P. A., Tang, S.-J., & Smith, P. A. (2021) · Frontiers in Pain Research · doi:10.3389/fpain.2021.698157 · Cited by 102 · see citing works
Microglial modulation of neuronal activity in the healthy brain
York, E. M., Bernier, L., & MacVicar, B. A. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22571 · Cited by 98 · see citing works
Li, X., Shi, H., Zhang, D., Jing, B., Chen, Z., Zheng, Y., Chang, S., Gao, L., & Zhao, G. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14211 · Cited by 96 · see citing works
Dou, B., Li, Y., Ma, J., Xu, Z., Fan, W., Tian, L., Chen, Z., Li, N., Gong, Y., Lyu, Z., et al. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.695670 · Cited by 92 · see citing works
Freria, C. M., Hall, J. C. E., Wei, P. Y., Guan, Z., McTigue, D. M., & Popovich, P. G. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2841-16.2017 · Cited by 90 · see citing works
Rossetti, A. C., Papp, M., Gruca, P., Paladini, M. S., Racagni, G., Riva, M. A., & Molteni, R. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.10.022 · Cited by 84 · see citing works
Neuroimmune signatures in chronic low back pain subtypes
Alshelh, Z., Brusaferri, L., Saha, A., Morrissey, E. J., Knight, P. C., Kim, M., Zhang, Y., Hooker, J. M., Albrecht, D., Torrado-Carvajal, Á., et al. (2021) · Brain · doi:10.1093/brain/awab336 · Cited by 86 · see citing works
Rosa, J. M., Farré‐Alins, V., Ortega, M. C., Navarrete, M., López-Rodríguez, A. B., Palomino‐Antolín, A., Fernández‐López, E., Sol, V. V., Decouty‐Pérez, C., Narros‐Fernández, P., et al. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15488 · Cited by 81 · see citing works
Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture
Li, W.-W., Guo, T.-Z., Shi, X., Sun, Y., Wei, T., Clark, D. J., & Kingery, W. S. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.09.036 · Cited by 80 · see citing works
Nociceptive signaling mediated by P2X3, P2X4 and P2X7 receptors
Inoue, K., & Tsuda, M. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114309 · Cited by 78 · see citing works
Microglia-Mediated Regulation of Neuropathic Pain: Molecular and Cellular Mechanisms
Tsuda, M. (2019) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00715 · Cited by 79 · see citing works
l ‐DOPA‐induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?
Carta, A. R., Mulas, G., Bortolanza, M., Duarte, T. T., Pillai, E., Fisone, G., Raisman‐Vozari, R., & Bel, E. A. D. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13482 · Cited by 80 · see citing works
The neuroinflammatory component of negative affect in patients with chronic pain
Albrecht, D., Kim, M., Akeju, O., Torrado-Carvajal, Á., Edwards, R. R., Zhang, Y., Bergan, C., Protsenko, E., Kucyi, A., Wasan, A. D., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0433-1 · Cited by 77 · see citing works
Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins
Swanson, A., Wolf, T., Sitzmann, A., & Willette, A. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.02.015 · Cited by 72 · see citing works
Role of microglia and P2X4 receptors in chronic pain
Kohno, K., & Tsuda, M. (2021) · PAIN Reports · doi:10.1097/pr9.0000000000000864 · Cited by 66 · see citing works
How microglia contribute to the induction and maintenance of neuropathic pain
Malcangio, M., & Sideris-Lampretsas, G. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00914-5 · Cited by 66 · see citing works
Self-citationMicroglia and Parkinson's disease: footprints to pathology
Lazdon, E., Stolero, N., & Frenkel, D. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02154-6 · Cited by 61 · see citing works
Tay, T. L., Carrier, M., & Tremblay, M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-9913-8_6 · Cited by 61 · see citing works
Microglia maintain the normal structure and function of the hippocampal astrocyte network
Du, Y., Brennan, F. H., Popovich, P. G., & Zhou, M. (2022) · Glia · doi:10.1002/glia.24179 · Cited by 61 · see citing works
Dodds, K. N., Beckett, E. A. H., Evans, S., Grace, P. M., Watkins, L. R., & Hutchinson, M. R. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.168 · Cited by 61 · see citing works
Fan, Z., Dou, B., Wang, J., Wu, Y., Du, S., Li, J., Yao, K., Li, Y., Wang, S., Gong, Y., et al. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1239839 · Cited by 59 · see citing works
Mironets, E., Osei‐Owusu, P., Bracchi-Ricard, V. C., Fischer, R., Owens, E. A., Ricard, J., Wu, D., Saltos, T. M., Collyer, E., Hou, S., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.2376-17.2018 · Cited by 59 · see citing works
Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy
Chuan-da, L., Zhao, J., Chen, J., Lu, J., Zhang, M., Huang, Q., Cao, Y., Jia, G., Tao, Y., Li, J., et al. (2019) · Endocrine · doi:10.1007/s12020-019-01880-6 · Cited by 58 · see citing works
The force awakens: insights into the origin and formation of microglia
Tay, T. L., Hagemeyer, N., & Prinz, M. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.04.003 · Cited by 59 · see citing works
Cantaut-Belarif, Y., Antri, M., Pizzarelli, R., Colasse, S., Vaccari, I., Soares, S., Renner, M., Dallel, R., Triller, A., & Bessis, A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201607048 · Cited by 56 · see citing works
Activated microglia facilitate the transmission of α-synuclein in Parkinson's disease
Zheng, T., & Zhang, Z. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105094 · Cited by 54 · see citing works
Synaptoimmunology - roles in health and disease
Nisticò, R., Salter, E. W., Nicolas, C. S., Feligioni, M., Mango, D., Bortolotto, Z. A., Gressèns, P., Collingridge, G. L., & Peineau, S. (2017) · Molecular Brain · doi:10.1186/s13041-017-0308-9 · Cited by 49 · see citing works
Kambrun, C., Roca‐Lapirot, O., Salio, C., Landry, M., Moqrich, A., & Feuvre, Y. L. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.068 · Cited by 59 · see citing works
Microglia exit the CNS in spinal root avulsion
Green, L. A., Nebiolo, J. C., & Smith, C. J. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000159 · Cited by 52 · see citing works
Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats
Marshall, S. A., McClain, J. A., Wooden, J. I., & Nixon, K. (2020) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2020.00052 · Cited by 51 · see citing works
Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain
Parusel, S., Yi, M., Hunt, C., & Wu, L. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00937-3 · Cited by 51 · see citing works
Immune drivers of physiological and pathological pain
Jain, A., Hakim, S., & Woolf, C. J. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20221687 · Cited by 58 · see citing works
“Neuroinflammation”: does it have a role in chronic pain? Evidence from human imaging
Loggia, M. L. (2024) · Pain · doi:10.1097/j.pain.0000000000003342 · Cited by 51 · see citing works
Si, W., Li, X., Jing, B., Chang, S., Zheng, Y., Chen, Z., Zhao, G., & Zhang, D. (2023) · Phytotherapy Research · doi:10.1002/ptr.8039 · Cited by 52 · see citing works
Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease
Camacho-Hernández, N. P., & Peña‐Ortega, F. (2023) · Neural Plasticity · doi:10.1155/2023/4637073 · Cited by 52 · see citing works
Neuropathic pain; what we know and what we should do about it
Smith, P. A. (2023) · Frontiers in Pain Research · doi:10.3389/fpain.2023.1220034 · Cited by 49 · see citing works
Neuroinflammation in l-DOPA-induced dyskinesia: beyond the immune function
Pisanu, A., Boi, L., Mulas, G., Spiga, S., Fenu, S., & Carta, A. R. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1874-4 · Cited by 49 · see citing works
Spinal microglia-neuron interactions in chronic pain
Ho, I. H. T., Chan, M. T. V., Wu, W. K. K., & Liu, X. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0520-695r · Cited by 49 · see citing works
Hu, D., Zhu, S., & Potas, J. R. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0679-3 · Cited by 47 · see citing works
Montague-Cardoso, K., Pitcher, T., Chisholm, K. I., Salera, G., Lindström, E., Hewitt, E. L., Solito, E., & Malcangio, M. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.10.018 · Cited by 45 · see citing works
Self-citationThe chemokine CXCL16 modulates neurotransmitter release in hippocampal CA1 area
Castro, M. A. D., Trettel, F., Milior, G., Maggi, L., Ragozzino, D., & Limatola, C. (2016) · Scientific Reports · doi:10.1038/srep34633 · Cited by 45 · see citing works
Microglia in health and pain: impact of noxious early life events
Burke, N. N., Fan, C. Y., & Trang, T. (2016) · Experimental Physiology · doi:10.1113/ep085714 · Cited by 43 · see citing works
Zhang, T., Zhang, M., Cui, S., Liang, W., Jia, Z., Guo, F., Ou, W., Wu, Y., & Zhang, S. (2023) · Brain and Behavior · doi:10.1002/brb3.2868 · Cited by 42 · see citing works
Activity-triggered tetrapartite neuron–glial interactions following peripheral injury
Ren, K., & Dubner, R. A. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.09.006 · Cited by 42 · see citing works
The Role of ATP Receptors in Pain Signaling
Inoue, K. (2022) · Neurochemical Research · doi:10.1007/s11064-021-03516-6 · Cited by 42 · see citing works
Regulation of neuropathic pain by microglial Orai1 channels
Tsujikawa, S., DeMeulenaere, K. E., Centeno, M. V., Ghazisaeidi, S., Martin, M. E., Tapies, M. G. R., Maneshi, M. M., Yamashita, M., Stauderman, K. A., Apkarian, A. V., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade7002 · Cited by 42 · see citing works
Fractalkine/CX3CR1 Pathway in Neuropathic Pain: An Update
Silva, R., & Malcangio, M. (2021) · Frontiers in Pain Research · doi:10.3389/fpain.2021.684684 · Cited by 41 · see citing works
Self-citationMicroglia in the CNS and Neuropathic Pain
Tsuda, M. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1756-9_7 · Cited by 39 · see citing works
The Role of Neuro-Immune Interactions in Chronic Pain: Implications for Clinical Practice
Su, P. P., Zhang, L., He, L., Zhao, N., & Guan, Z. (2022) · Journal of Pain Research · doi:10.2147/jpr.s246883 · Cited by 41 · see citing works
Barkaway, A., Attwell, D., & Korte, N. (2022) · Neurophotonics · doi:10.1117/1.nph.9.3.031914 · Cited by 28 · see citing works
Presynaptic Inhibition of Primary Nociceptive Signals to Dorsal Horn Lamina I Neurons by Dopamine
Lu, Y., Doroshenko, M., Lauzadis, J., Kanjiya, M. P., Rebecchi, M. J., Kaczocha, M., & Puopolo, M. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0323-18.2018 · Cited by 38 · see citing works
Microglial heterogeneity in chronic pain
Sideris-Lampretsas, G., & Malcangio, M. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.06.005 · Cited by 37 · see citing works
Self-citationSpinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity
Gu, N., Yi, M., Murugan, M., Xie, M., Parusel, S., Peng, J., Eyo, U. B., Hunt, C., Dong, H., & Wu, L. (2022) · Molecular Brain · doi:10.1186/s13041-022-00970-3 · Cited by 36 · see citing works
Complement 3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling
Doolen, S., Cook, J., Riedl, M. S., Kitto, K. F., Kohsaka, S., Honda, C. N., Fairbanks, C. A., Taylor, B. K., & Vulchanova, L. (2017) · Glia · doi:10.1002/glia.23208 · Cited by 35 · see citing works
Yang, N. J., Isensee, J., Neel, D. V., de Quadros, A. U., Zhang, H.-X. B., Lauzadis, J., Liu, S. M., Shiers, S. I., Belu, A., Palan, S., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00973-8 · Cited by 34 · see citing works
Diversity of composition and function of sodium channels in peripheral sensory neurons
Dib‐Hajj, S. D., & Waxman, S. G. (2015) · Pain · doi:10.1097/j.pain.0000000000000353 · Cited by 35 · see citing works
Adult and endemic neurogenesis in the vestibular nuclei after unilateral vestibular neurectomy
Rastoldo, G., Mahmoudi, N. E., Marouane, E., Péricat, D., Watabe, I., Toneto, A., López‐Juárez, A., Chabbert, C., & Tighilet, B. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101899 · Cited by 33 · see citing works
Spinal pain processing in arthritis: Neuron and glia (inter)actions
Schaible, H., König, C., & Ebersberger, A. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15742 · Cited by 33 · see citing works
VGF: A prospective biomarker and therapeutic target for neuroendocrine and nervous system disorders
Wang, Y., Qin, X., Han, Y. J., & Li, B. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113099 · Cited by 33 · see citing works
Schwann cell-secreted PGE2 promotes sensory neuron excitability during development
Kantarci, H., Elvira, P. D., Thottumkara, A. P., O’Connell, E. M., Iyer, M., Donovan, L. J., Dugan, M. Q., Ambiel, N., Granados, A. A., Zeng, H., et al. (2024) · Cell · doi:10.1016/j.cell.2024.07.033 · Cited by 31 · see citing works
Microglial role in the development of chronic pain
Suter, M. R. (2016) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000000373 · Cited by 30 · see citing works
Sauerstein, K., Liebelt, J., Namer, B., Schmidt, R., Rukwied, R., & Schmelz, M. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.03.006 · Cited by 31 · see citing works
The role of glia in Parkinson's disease: Emerging concepts and therapeutic applications
Kuter, K. Z., Cenci, M. A., & Carta, A. R. (2020) · Progress in brain research · doi:10.1016/bs.pbr.2020.02.004 · Cited by 31 · see citing works
Marouane, E., Mahmoudi, N. E., Rastoldo, G., Péricat, D., Watabe, I., Lapôtre, A., Tonetto, A., Xavier, F., Dumas, O., Chabbert, C., et al. (2021) · Cells · doi:10.3390/cells10123377 · Cited by 31 · see citing works
Hippocampal neuroplasticity and inflammation: relevance for multiple sclerosis
Mancini, A., Gaetani, L., Gregorio, M. D., Tozzi, A., Ghiglieri, V., Calabresi, P., & Filippo, M. D. (2017) · Multiple Sclerosis and Demyelinating Disorders · doi:10.1186/s40893-017-0019-1 · Cited by 30 · see citing works
Liang, J.-H., Yu, H., Xia, C., Zheng, Y., Zhang, Z., Chen, Y., Raza, M. A., Wu, L. H., & Yan, H. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117006 · Cited by 29 · see citing works
Reischer, G., Heinke, B., & Sandkühler, J. (2020) · Molecular Pain · doi:10.1177/1744806920917249 · Cited by 29 · see citing works
Self-citationSnapshot of microglial physiological functions
Verkhratsky, A., Sun, D., & Tanaka, J. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104960 · Cited by 28 · see citing works
Lecchi, C., Costa, E. D., Lebelt, D., Ferrante, V., Canali, E., Ceciliani, F., Stucke, D., & Minero, M. (2017) · animal · doi:10.1017/s1751731117001525 · Cited by 28 · see citing works
The Effects of Peripheral Inflammation on the Brain—A Neuroimaging Perspective
Millett, C. E., Burdick, K. E., & Kubicki, M. R. (2022) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000323 · Cited by 27 · see citing works
Sessler, K., Blechschmidt, V., Hoheisel, U., Mense, S., Schirmer, L., & Treede, R. (2021) · Journal of Neurophysiology · doi:10.1152/jn.00348.2020 · Cited by 27 · see citing works
Zhang, J., Mense, S., Treede, R., & Hoheisel, U. (2017) · Journal of Neurophysiology · doi:10.1152/jn.00680.2016 · Cited by 26 · see citing works
López-Rodríguez, A. B., Decouty‐Pérez, C., Farré‐Alins, V., Palomino‐Antolín, A., Narros‐Fernández, P., & Egea, J. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14081550 · Cited by 25 · see citing works
Espinoza, A. P. V., Na, N., Campanati, L., Ngo, P., Baldwin, K. K., & Cline, H. T. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2516103122 · Cited by 23 · see citing works
VGF: a biomarker and potential target for the treatment of neuropathic pain?
Soliman, N., Okuse, K., & Rice, A. S. C. (2019) · PAIN Reports · doi:10.1097/pr9.0000000000000786 · Cited by 22 · see citing works
Dodds, K. N., Beckett, E. A. H., Evans, S., & Hutchinson, M. R. (2018) · Reproductive Sciences · doi:10.1177/1933719118773405 · Cited by 24 · see citing works
- Authors
- Clark, A. K., Gruber-Schoffnegger, D., Drdla-Schutting, R., Gerhold, K. J., Malcangio, M., & Sandkühler, J.
- Affiliations
- King's College London (GB)
- Medical University of Vienna (AT)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-03-18
- Volume
- 35
- Issue
- 11
- Pages
- 4552-4570
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4363384
- OpenAlex
- W2063244116
- Cited by
- 171
- References
- 65
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 12 · 2023: 15 · 2022: 18 · 2021: 23 · 2020: 14 · 2019: 15 · 2018: 18 · 2017: 12 · 2016: 18 · 2015: 9
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (093173/Z/10/Z)
- Austrian Science Fund
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, synaptic plasticity, synaptic facilitation, CX3CR1, fractalkine, IL-1β, eicosanoids, presynaptic neurotransmitter release, nociceptive pathways, dorsal horn, C-fibers, pain amplification, chronic pain, glial cells
- MeSH terms
- Animals, Male, Synaptic Transmission, Neuronal Plasticity, Organ Culture Techniques, Spinal Cord, Rats, Sprague-Dawley, Microglia, Excitatory Postsynaptic Potentials, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
