The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
P2X7-Dependent Release of Interleukin-1β and Nociception in the Spinal Cord following Lipopolysaccharide
Open accessAbstract
The cytokine interleukin-1β (IL-1β) released by spinal microglia in enhanced response states contributes significantly to neuronal mechanisms of chronic pain. Here we examine the involvement of the purinergic P2X7 receptor in the release of IL-1β following activation of Toll-like receptor-4 (TLR4) in the dorsal horn, which is associated with nociceptive behavior and microglial activation. We observed that lipopolysaccharide (LPS)-induced release of IL-1β was prevented by pharmacological inhibition of the P2X7 receptor with A-438079, and was absent in spinal cord slices taken from P2X7 knock-out mice. Application of ATP did not evoke release of IL-1β from the dorsal horn unless preceded by an LPS priming stimulus, and this release was dependent on P2X7 receptor activation. Extensive phosphorylation of p38 MAPK in microglial cells in the dorsal horn was found to correlate with IL-1β secretion following both LPS and ATP. In behavioral studies, intrathecal injection of LPS in the lumbar spinal cord produced mechanical hyperalgesia in rat hindpaws, which was attenuated by concomitant injections of either a nonspecific (oxidized ATP) or a specific (A-438079) P2X7 antagonist. In addition, LPS-induced hypersensitivity was observed in wild-type but not P2X7 knock-out mice. These data suggest a critical role for the P2X7 receptor in the enhanced nociceptive transmission associated with microglial activation and secretion of IL-1β in the dorsal horn. We suggest that CNS-penetrant P2X7 receptor antagonists, by targeting microglia in pain-enhanced response states, may be beneficial for the treatment of persistent pain.
Overview
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
Verification
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?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“P2X7 inhibition has been associated with antidepressant-like effects, and IL-1β knockout mice failed to express these receptors [48,49].”
From Selected biomarkers of depression: what are the effects of cytokines and inflammation (2022) · cites this paper as [49]
Experimental — accuracy not yet measuredIn the citing paper
“P2X7 inhibition has been associated with antidepressant-like effects, and IL-1β knockout mice failed to express these receptors [48,49].”
From Selected biomarkers of depression: what are the effects of cytokines and inflammation (2022) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Quantitative assessment of tactile allodynia in the rat paw
Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)90144-9 · Cited by 7,740
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080
Efficient Analysis of Experimental Observations
Dixon, W. J. (1980) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.20.040180.002301 · Cited by 2,216
Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf
Mariathasan, S., Newton, K., Monack, D. M., Vucic, D., French, D. M., Lee, W. P., Roose-Girma, M., Erickson, S. L., & Dixit, V. M. (2004) · Nature · doi:10.1038/nature02664 · Cited by 1,864
P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury
Tsuda, M., Shigemoto‐Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M. W., & Inoue, K. (2003) · Nature · doi:10.1038/nature01786 · Cited by 1,567
Pannexin‐1 mediates large pore formation and interleukin‐1β release by the ATP‐gated P2X7 receptor
Pelegrı́n, P., & Surprenant, A. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601378 · Cited by 1,490
Pathological and protective roles of glia in chronic pain
Milligan, E. D., & Watkins, L. R. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2533 · Cited by 1,443
The P2X7 Receptor: A Key Player in IL-1 Processing and Release
Ferrari, D., Pizzirani, C., Adinolfi, E., Lemoli, R. M., Curti, A., Idzko, M., Panther, E., & Di Virgilio, F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.3877 · Cited by 1,025
Cited by
Sorted by citations
Items 101–200 of 296
Emerging role of P2X7 receptors in CNS health and disease
Tewari, M., & Seth, P. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.10.001 · Cited by 80
Yan, X., Jiang, E., & Weng, H.-R. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0222-3 · Cited by 77
“It has been known that IL-1β is released from microglia activated by LPS [27] and IL-1β receptors are expressed in spinal dorsal horn neurons [33].”
Inhibition of the P2X7 Receptor Reduces Cystogenesis in PKD
Chang, M., Lu, J., Tian, Y., Chen, Y., Hung, C., Huang, Y.-H., Chen, Y., Wu, M.-S., Yang, C., & Cheng, Y. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010070728 · Cited by 70
Mechanisms of Transmission and Processing of Pain: A Narrative Review
Maio, G. D., Villano, I., Ilardi, C. R., Messina, A., Monda, V., Iodice, A. C., Porro, C., Panaro, M. A., Chieffi, S., Messina, G., et al. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20043064 · Cited by 83
“Among the numerous immune-derived or gliaderived mediators that are involved in pain hypersensitivity, interleukin-1β (IL-1β) is a key cytokine that modulates microglia, astrocytes, and neurons [96,97].”
BackgroundJin, X., Chen, X., Zheng, B., & Wang, X. (2015) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000001097 · Cited by 69
P2X7 Antagonists as Potential Therapeutic Agents for the Treatment of CNS Disorders
Chrovian, C. C., Rech, J. C., Bhattacharya, A., & Letavic, M. A. (2014) · Progress in medicinal chemistry · doi:10.1016/b978-0-444-63380-4.00002-0 · Cited by 69
Microglial toll-like receptors and Alzheimer’s disease
Su, F., Bai, F., Zhou, H., & Zhang, Z. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.10.010 · Cited by 69
“Moreover, the involvement of the purinergic P2X7 receptor in both microglia-mediated release of pro-inflammatory cytokines and phagocytosis of injured cells following TLR4 activation has been demonstrated (Clark et al., 2010).”
Lenertz, L. Y., Gavala, M. L., Zhu, Y., & Bertics, P. J. (2011) · Immunologic Research · doi:10.1007/s12026-011-8203-4 · Cited by 71
“With respect to pain research, several reports have shown that P2X7 is involved in promoting inflammatory and neuropathic pain [45, 46].”
BackgroundChen, L., Lv, X., Guo, Q., Lv, S., Lü, N., Xu, W., Yu, J. M., & Zhang, Y. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15994 · Cited by 68
Sauer, R., Hackel, D., Morschel, L., Sahlbach, H., Wang, Y., Mousa, S. A., Roewer, N., Brack, A., & Rittner, H. L. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-10 · Cited by 64
“Intrathecal injection of LPS in the lumbar spinal cord produces mechanical hyperalgesia in rat hind-paws dependent on purigergic receptors [47].”
BackgroundThe Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain
McGinnis, A., & Ji, R. (2023) · Cells · doi:10.3390/cells12060965 · Cited by 67
“Instead, P2X7 is highly expressed by spinal microglia, which upregulate it following nerve injury in a pro-nociceptive manner [154,155].”
BackgroundATP and P2X Purinoceptors in Urinary Tract Disorders
Ford, A. P. D. W., & Cockayne, D. A. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-16499-6_22 · Cited by 64
Asatryan, L., Ostrovskaya, O. I., Lieu, D. K., & Davies, D. L. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.09.030 · Cited by 63
“P2X7Rs have been shown tomodulate the release of IL-1b, a recognizedmediator of neurodegeneration and pain sensation (Clark et al., 2010; Honore et al., 2009; Takenouchi et al., 2008).”
BackgroundNeuromodulation, Specialized Proresolving Mediators, and Resolution of Pain
Tao, X., Lee, M. S., Donnelly, C. R., & Ji, R. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00892-9 · Cited by 63
Involvement of P2X7 receptors in chronic pain disorders
Ren, W., & Illés, P. (2021) · Purinergic Signalling · doi:10.1007/s11302-021-09796-5 · Cited by 62
“(2) In P2X7R deficient mice, the LPS-induced release of IL-1β from the peritoneal lavage of macrophages was abrogated [43] and the intrathecal LPS-induced mechanical hypersensitivity in the hindpaws was blocked [44].”
BackgroundMesuret, G., Engel, T., Hessel, E. V. S., Sanz‐Rodriguez, A., Jimenez‐Pacheco, A., Miras‐Portugal, M. T., Dı́az-Hernández, M., & Henshall, D. C. (2014) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12272 · Cited by 62
“IL1b release [32], and we also detected an increase in IL1b protein levels after SE in the model (Figure 2D).”
Macrophages and microglia in inflammation and neuroinflammation underlying different pain states
Ouyang, C., Luo, X., & Ji, R. (2023) · Medical Review · doi:10.1515/mr-2023-0034 · Cited by 67
Astrocytes—Multitaskers in chronic pain
Hansen, R. B., & Malcangio, M. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.03.023 · Cited by 61
Self-citationNociceptive transmission and modulation via P2X receptors in central pain syndrome
Kuan, Y., & Shyu, B. (2016) · Molecular Brain · doi:10.1186/s13041-016-0240-4 · Cited by 60
“A-438079 was shown to block both the ATP- and lipopolysaccharide (LPS)-induced release of IL-1β [43].”
BackgroundLong-term potentiation of glycinergic synapses triggered by interleukin 1β
Chirila, A. M., Brown, T. E., Bishop, R. A., Bellono, N. W., Pucci, F. G., & Kauer, J. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1401013111 · Cited by 56
Ficker, C., Rozmer, K., Kató, E., Andó, R. D., Schumann, L., Krügel, U., Franke, H., Sperlágh, B., Riedel, T., & Illés, P. (2014) · Glia · doi:10.1002/glia.22707 · Cited by 59
Lim, J. C.-S., Lu, W., Beckel, J. M., & Mitchell, C. H. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00270 · Cited by 59
“, 2009; Stanley and Lacy, 2010), and the stimulation of P2X7Rs is associated with cytokine release from multiple cell types (Pizzirani et al., 2007; Mingam et al., 2008; Clark et al., 2010), this study asked whether neurons could release cytokines in response to mechanical strain, whether this involved P2X7Rs, and pro…”
BackgroundDworsky-Fried, Z., Kerr, B. J., & Taylor, A. M. W. (2020) · Neurobiology of Pain · doi:10.1016/j.ynpai.2020.100045 · Cited by 64
“LPS derived from gram-negative bacteria binds TLR4 expressed on microglial cells and promotes microglial activation and the production of proinflammatory molecules (Clark et al., 2010; Lehnard et al., 2002; Saito et al., 2010).”
BackgroundPro-survival effects of JNK and p38 MAPK pathways in LPS-induced activation of BV-2 cells
Svensson, C., Part, K., Künnis-Beres, K., Kaldmäe, M., Fernaeus, S. Z., & Land, T. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.02.083 · Cited by 56
“However, intrathecal injection of LPS in rats resulted in microglial activation, extensive phosphorylation of p38 MAPK and a subsequent release of IL-1b [22].”
BackgroundKeating, C. D., Pelegrı́n, P., Martínez, C. M., & Grundy, D. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100423 · Cited by 56
“Furthermore, P2X7Rdependent release of IL-1b was implicated in mediating LPSinduced hypersensitivity in the spinal cord associated with microglial activation (8).”
BackgroundInfluentialItoh, K., Chiang, C., Li, Z., Lee, J., Dostrovsky, J. O., & Sessle, B. J. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.083 · Cited by 56
“proinflammatory cytokines from microglia which readily enhance synaptic transmission (Fields and Burnstock, 2006; Sperlágh and Illes, 2007; Surprenant and North, 2009; Clark et al., 2010).”
InfluentialNeuroinflammation and Post-Stroke Depression: Focus on the Microglia and Astrocytes
Lu, W., & Wen, J. (2024) · Aging and Disease · doi:10.14336/ad.2024.0214-1 · Cited by 64
“IL-1β is linked to the P2X receptor family, activation of the P2X7-NLRP3-IL-1β pathway is connected with depressive-like behaviors [64], and inhibition of P2X7 is connected with antidepressant-like effects [65].”
Biological Roles of Resolvins and Related Substances in the Resolution of Pain
Lim, J. Y., Park, C., & Hwang, S. W. (2015) · BioMed Research International · doi:10.1155/2015/830930 · Cited by 57
Ma, M., Ren, Q., Zhang, J.-C., & Hashimoto, K. (2014) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2014.12.1.31 · Cited by 55
Differential expression of P2X7 receptor and IL-1β in nociceptive and neuropathic pain
Luchting, B., Heyn, J., Woehrle, T., Rachinger-Adam, B., Kreth, S., Hinske, L. C., & Azad, S. C. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0565-z · Cited by 54
“Lesion of a peripheral nerve leads to both a transition of microglia to the side of damage and an infiltration of immune cells in the vicinity of the synapse between primary afferent fibers and nociceptive neurons in the dorsal horn of the spinal cord [41, 42].”
BackgroundZhong, S., Zhou, Z., Liang, Y., Cheng, X., Li, Y., Teng, W., Zhao, M., Liu, C., Guan, M., & Zhao, C. (2019) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2019.1608905 · Cited by 56
“Conversely, Enterococcus faecium was found to have increased after chemotherapy and it can induce elevated production of TNF-a and IL-6 (Kim 2011).”
BackgroundInfluentialZhou, W., Dantzer, R., Budac, D. P., Walker, A. K., Mao‐Ying, Q., Lee, A. W., Heijnen, C. J., & Kavelaars, A. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.01.013 · Cited by 57
“In models of persistent peripheral inflammation or in models of neuropathic pain, inflammatory cytokines produced by spinal cord microglia and astrocytes contribute to the pain response (Clark et al., 2010; Ikeda et al., 2012; Eijkelkamp et al., 2010).”
BackgroundStokes, J. A., Corr, M., & Yaksh, T. L. (2013) · Pain · doi:10.1016/j.pain.2013.01.012 · Cited by 56
de Quadros, A. U., Pinto, L. G., Fonseca, M. M., Kusuda, R., Cunha, F. Q., & Cunha, T. M. (2015) · Scientific Reports · doi:10.1038/srep14648 · Cited by 52
P2X7 receptor in inflammation and pain
Hu, S.-Q., Hu, J., Zou, F.-L., Liu, J., Luo, H., Hu, D.-X., Wu, L., & Zhang, W. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.07.006 · Cited by 52
Jin, X., Wang, L., Jian-ling, Z., Yang, J., & Liu, S. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23443 · Cited by 51
“Previous studies (Clark et al., 2010) have shown that the P2X7 purinoceptor (P2X7R) is involved in the release of IL-1b following activation of toll-like receptor-4 (TLR4) in the dorsal horn, which is associated with nociceptive behavior and microglial activation.”
BackgroundMethodResultInfluentialPurinergic system, microglia and neuropathic pain
Tsuda, M., Tozaki‐Saitoh, H., & Inoue, K. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.10.014 · Cited by 51
ATP in neuron–glia bidirectional signalling
Verderio, C., & Matteoli, M. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2010.04.007 · Cited by 51
Lin, J., Liu, F., Zhang, Y., Song, N., Liu, M., Fang, X., Liao, D., Zhou, C., Wang, H., & Shen, J. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28726 · Cited by 51
“Besides, spinal microglia were activated by ATP via P2X4 receptor and P2X7 receptor leading to the release of IL‐1β (Clark et al., 2010; Mehta et al., 2014).”
Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor
Wen, L., Tang, L., Zhang, M., Wang, C., Li, S., Wen, Y., Tu, H., Tian, H., Wei, J., Liang, P., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116159 · Cited by 50
“It was also suggested that the P2X7 receptors could regulate the production of IL-1β, thus inducing inflammation and neuropathic pain [21,22].”
BackgroundZhang, Y., Yang, Y., Li, H., Feng, Q., Ge, W., & Xu, X. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03563-w · Cited by 55
Systems and Circuits Linking Chronic Pain and Circadian Rhythms
Warfield, A. E., Prather, J. F., & Todd, W. D. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.705173 · Cited by 49
“Activation of P2X7 leads to IL-1 β release (Clark et al., 2010), as does activation of TLR2 and TLR4 (Tanga et al., 2005; Kim et al., 2007).”
BackgroundNeuropathic 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 53
Zhu, W., Acosta, C., Macneil, B. J., Cortes, C., Intrater, H. M., Gong, Y., & Namaka, M. (2013) · BioMed Research International · doi:10.1155/2013/480702 · Cited by 51
Cell-autonomous regulation of hematopoietic stem cell cycling activity by ATP
Casati, A., Frascoli, M., Traggiai, E., Proietti, M., Schenk, U., & Grassi, F. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.107 · Cited by 51
Gonzaga, D. T. G., Ferreira, L. B. G., Costa, T. E. M. M., von Ranke, N. L., Pacheco, P. A. F., Simões, A., Arruda, J. C., Dantas, L. P., Freitas, H. R., Reis, R. A. D. M., et al. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.08.034 · Cited by 49
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 50
Greve, A., Skals, M., Fagerberg, S. K., Tonnus, W., Ellermann‐Eriksen, S., Evans, R. J., Linkermann, A., & Prætorius, H. A. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00113 · Cited by 46
“…for its importance in immune cell communication (Di Virgilio and Vuerich, 2015), release of pro-inflammatory cytokines (Suzuki et al., 2004; Clark et al., 2010; Shieh et al., 2014; Trubiani et al., 2014), and recruitment of macrophages and lymphocytes (Moncao-Ribeiro et al., 2011; da Silva…”
BackgroundLiu, P.-W., Yue, M.-X., Zhou, R., Niu, J., Huang, D., Xu, T., Luo, P., Liu, X., & Zeng, J. (2017) · Journal of Pain Research · doi:10.2147/jpr.s137131 · Cited by 45
“states contributes significantly to neuronal mechanisms of chronic pain.(15) Furthermore, intrathecal administration of IL-1b induced thermal hyperalgesia by activating the iNOS-NO cascade in the intact rat spinal cord.”
Andó, R. D., & Sperlágh, B. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2012.09.016 · Cited by 44
Wang, C., Song, S., Zhang, Y., Ge, Y., Fang, X., Huang, T., Du, J., & Gao, J. (2015) · Scientific Reports · doi:10.1038/srep14553 · Cited by 43
Microglia Phenotypes Following the Induction of Alcohol Dependence in Adolescent Rats
Peng, H., & Nixon, K. (2021) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.14504 · Cited by 43
The Role of ATP Receptors in Pain Signaling
Inoue, K. (2022) · Neurochemical Research · doi:10.1007/s11064-021-03516-6 · Cited by 42
“P2X7R is essential for ATP-induced IL-1β release from TLR4-primed microglia [121].”
BackgroundCurto-Reyes, V., Kirschmann, G., Pertin, M., Drexler, S. K., Décosterd, I., & Suter, M. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133707 · Cited by 42
Peripheral Inflammatory Hyperalgesia Depends on P2X7 Receptors in Satellite Glial Cells
Neves, A. F., Farias, F. H., de Magalhães, S. F., Araldi, D., Pagliusi, M., Tambeli, C. H., Sartori, C. R., Lotufo, C. M. D. C., & Parada, C. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00473 · Cited by 42
“Several reports emphasize that ATP-mediated P2X7R activation is essential for rapid maturation and release of IL-1β from activated immune cells, including macrophages and microglial cells (Ferrari et al., 2006; Clark et al., 2010; Stoffels et al., 2015; Giuliani et al., 2017).”
BackgroundFractalkine/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
“The activation of this receptor leads to the phosphorylation of p38 MAPK pathway contributing to the release of proinflammatory cytokines, such as IL-1β to the extracellular environment (66).”
BackgroundSelf-citationNicol, L. S. C., Thornton, P., Hatcher, J. P., Glover, C. P. J., Webster, C. I., Burrell, M. R., Hammett, K. M., Jones, C. A., Sleeman, M. A., Billinton, A., et al. (2017) · Pain · doi:10.1097/j.pain.0000000000001130 · Cited by 41
“Slides were then cover slipped with vectashield mounting medium with DAPI (Vector Laboratories, Peterborough, United Kingdom), sealed with nail varnish and dried.(9)”
MethodMicroglia 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
Systemic inflammation and higher perception of dyspnea mimicking asthma in obese subjects
Carpio, C., Villasante, C., Galera, R., Romero, D., de Cos, A., Hernánz, Á., & Rio, F. G. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.11.010 · Cited by 41
Swanson, D. M., Savall, B. M., Coe, K. J., Schoetens, F., Koudriakova, T. B., Skaptason, J., Wall, J. L., Rech, J. C., Deng, X., Angelis, M. D., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00989 · Cited by 38
Functional and Metabolic Characterization of Microglia Culture in a Defined Medium
Montilla, A., Zabala, A., Matute, C., & Domercq, M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00022 · Cited by 40
“Since purinergic receptors, particularly P2Y12, P2 × 4 and P2 × 7, are pivotal in microglial activation and function (Clark et al., 2010; Beaino et al., 2017; Zabala et al., 2018), we checked whether the presence of serum influences purinergic receptor immunoreactivity.”
BackgroundPurinergic regulation of inflammasome activation after central nervous system injury
Bernier, L. (2012) · The Journal of General Physiology · doi:10.1085/jgp.201210875 · Cited by 37
“Among the many host-derived molecules that activate inflammasomes, ATP potently induces NLRP1- and Correspondence to Louis-Philippe Bernier: l o u i s - p h i l i p p e . b e r n i e r @ m a i l . m c g i l l . c a Abbreviations used in this paper: CNS, central nervous system; IL-1, interleukin-1; NLRP, NOD-like recep…”
BackgroundInfluentialWestlund, K. N., Zhang, L., Ma, F., & Oz, H. S. (2011) · Translational research · doi:10.1016/j.trsl.2011.10.003 · Cited by 35
Meng, X., Gao, J., Jian-ling, Z., Wang, L., Liu, S., Jin, X., Yao, M., & Namaka, M. (2017) · Neuroscience Research · doi:10.1016/j.neures.2017.06.006 · Cited by 36
The state-of-the-art pharmacotherapeutic options for the treatment of chronic non-cancer pain
D'Souza, R. S., Langford, B. J., Wilson, R. E., Her, Y. F., Schappell, J. B., Eller, J. S., Evans, T. C., & Hagedorn, J. M. (2022) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2022.2060741 · Cited by 35
“nist called A-438079 also produced anti-nociception in a rat model where target tissues were previously sensitized [122].”
BackgroundActivity of sputum p38 MAPK is correlated with airway inflammation and reduced FEV1 in COPD patients
Gao, H. (2013) · Medical Science Monitor · doi:10.12659/msm.889880 · Cited by 34
P2X3 receptors and sensitization of autonomic reflexes
Ford, A. P. D. W., Undem, B. J., Birder, L. A., Grundy, D., Pijacka, W., & Paton, J. F. R. (2015) · Autonomic Neuroscience · doi:10.1016/j.autneu.2015.04.005 · Cited by 34
“(P2X7Rs) are located predominantly on immune cells, such as macrophages andmicroglia, and their activation in response to cellular danger signals, such as high (N100 μM) concentrations of ATP, triggers a series of physiological events that culminates with the processing and release of the proinflammatory cytokine IL-1…”
BackgroundThe roles of purinergic signaling during gastrointestinal inflammation
Roberts, J. A., Lukewich, M. K., Sharkey, K. A., Furness, J. B., Mawe, G. M., & Lomax, A. E. (2012) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2012.09.011 · Cited by 34
Hansen, R. B., Vacca, V., Pitcher, T., Clark, A. K., & Malcangio, M. (2015) · Pain · doi:10.1097/j.pain.0000000000000416 · Cited by 34
“Lumbar spinal cords were excised to obtain horizontal dorsal horn slices with L3, L4, and L5 dorsal roots attached.(8,34) Slices were mounted in the”
MethodSelf-citationGuillot, X., Semerano, L., Decker, P., Falgarone, G., & Boissier, M. (2011) · Joint Bone Spine · doi:10.1016/j.jbspin.2011.10.008 · Cited by 33
Kanjanamekanant, K., Luckprom, P., & Pavasant, P. (2013) · Journal of Periodontal Research · doi:10.1111/jre.12139 · Cited by 33
Asatryan, L., Khoja, S., Rodgers, K. E., Alkana, R. L., Tsukamoto, H., & Davies, D. L. (2015) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2015.06.007 · Cited by 31
“Most importantly, P2X7Rs were shown to modulate the release of IL-1β, a recognized mediator of neurodegeneration (Bernardino et al., 2008; Clark et al., 2010;Honore et al., 2009; Takenouchi et al., 2008).”
BackgroundThe Purinergic System and Glial Cells: Emerging Costars in Nociception
Magni, G., & Ceruti, S. (2014) · BioMed Research International · doi:10.1155/2014/495789 · Cited by 32
“Moreover, it is now emerging that bioactive molecules contained in analgesic preparation from traditional Chinese medicine (such as tetramethylpyrazine, sodium ferulate, and puerarin) can inhibit P2X3-mediated transmission in primary afferent neurons [40].”
BackgroundHsieh, C.-T., Lee, Y., Lee, J. W., Lu, S., Tucci, M. A., Dai, X., Ojeda, N. B., Lee, H. J., Fan, L., & Tien, L. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104686 · Cited by 31
“In P2X7 knock-out mice with LPS exposure, the enhanced nociceptive transmission was strongly associated with the release of IL-1β by activated microglia in the dorsal horn of the spinal cord following activation of TLR-4 through the activation of P2X7 receptors of the spinal microglia (Clark et al., 2010).”
BackgroundInfluentialPain-related toxins in scorpion and spider venoms: a face to face with ion channels
Diochot, S. (2021) · The Journal of venomous animals and toxins including tropical diseases · doi:10.1590/1678-9199-jvatitd-2021-0026 · Cited by 31
“In the same way, P2X7 receptors stimulated during microglial inflammation are involved in the development of neuropathic and inflammatory pain [100].”
BackgroundIde, S., Nishizawa, D., Fukuda, K., Kasai, S., Hasegawa, J., Hayashida, M., Minami, M., & Ikeda, K. (2014) · Molecular Pain · doi:10.1186/1744-8069-10-75 · Cited by 31
Won, K. A., Kim, M. J., Yang, K. Y., Park, J. S., Lee, M. K., Park, M. K., Bae, Y. C., & Ahn, D. K. (2013) · Journal of Pain · doi:10.1016/j.jpain.2013.10.013 · Cited by 30
Nonneuronal central mechanisms of pain: glia and immune response.
Romero-Sandoval, E., & Sweitzer, S. (2015) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2014.11.007 · Cited by 33
Resveratrol attenuates inflammatory hyperalgesia by inhibiting glial activation in mice spinal cords
WANG, L.-L., Shi, D., Gu, H., Zheng, M., Hu, J., Song, X., SHEN, Y.-L., & CHEN, Y.-Y. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5027 · Cited by 30
Zhang, J., Li, X., Gao, Y., Guo, G., Xu, C., Li, G., Liu, S., Huang, A., Tu, G., Peng, H., et al. (2012) · Burns · doi:10.1016/j.burns.2012.08.013 · Cited by 29
“With respect to pain research, several reports have shown that P2X7 is involved in promoting inflammatory and neuropathic pain [35,36].”
BackgroundThe P2X7 Receptor as a Mechanistic Biomarker for Epilepsy
Engel, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065410 · Cited by 28
Safieh‐Garabedian, B., Nomikos, M., & Saadé, N. E. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.11.041 · Cited by 27
Aoyama, R., Okada, Y., Yokota, S., Yasui, Y., Fukuda, K., Shinozaki, Y., Yoshida, H., Nakamura, M., Chiba, K., Yasui, Y., et al. (2011) · Pain · doi:10.1016/j.pain.2011.05.014 · Cited by 27
Rubio‐Araiz, A., Pérez‐Hernández, M., Urrutia, A. A., Porcu, F., Borcel, É., Gutiérrez‐López, M. D., O’Shea, E., & Colado, M. I. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145714000145 · Cited by 27
“, 2009), and maturation and release of the pro-inflammatory cytokine IL-1β (Solle et al., 2001; Chakfe et al., 2002; Clark et al., 2010).”
BackgroundInfluentialSpinal mechanisms of neuropathic pain: Is there a P2X4-BDNF controversy?
Malcangio, M. (2017) · Neurobiology of Pain · doi:10.1016/j.ynpai.2017.04.001 · Cited by 27
“P2X7 receptor activation mediates the release of the cytokine IL-1 b and the lysosomal enzyme cathepsin S from microglia via a p38 MAP kinase pathway (Clark et al., 2010b).”
BackgroundSelf-citationBeaino, W., Janssen, B., Kooijman, E., Vos, R., Schuit, R., O'Brien-Brown, J., Kassiou, M., Hof, B. J. V. H., Vugts, D., de Vries, H. D., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01962-7 · Cited by 23
Arruda, J. C., Rocha, N. C., dos Santos, E., Ferreira, L. G. B., Bello, M. L., Penido, C., Costa, T. E. M. M., dos Santos, J. A. A., Ribeiro, I. M., Tomassini, T. C. B., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112006 · Cited by 26
Peripheral P2X7 receptor-induced mechanical hyperalgesia is mediated by bradykinin
Teixeira, J. M., Oliveira, M. C. G., Parada, C. A., & Tambeli, C. H. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.06.057 · Cited by 26
“Because the activation of spinal P2X7 receptors contributes to inflammatory hyperalgesia (Clark et al., 2010), the finding that the administration of A-438079 in the contralateral hind paw did not affect BzATP-induced mechanical hyperalgesia confirms that only local P2X7 receptors in the peripheral…”
P2X receptor-mediated ATP purinergic signaling in health and disease
Jiang, L. (2012) · Cell Health and Cytoskeleton · doi:10.2147/chc.s27196 · Cited by 26
Lee, W., Lee, S., Cho, J., Jung, K., Kim, J., Hiền, T. T., Kang, K. W., Ko, H., & Kim, Y. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm2012326 · Cited by 24
Fan, X., Wang, X., Han, J., Ding, X., Tang, S., & Ning, L. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03352-8 · Cited by 25
“It was reported that a variety of cytokines are involved in the generation of neuropathic pain, including IL-1β and IL-6, and their release is related to P2X7 [45, 49].”
BackgroundRoles of Phosphorylation of N-Methyl-d-Aspartate Receptor in Chronic Pain
Pan, L., Li, T., Wang, R., Deng, W., Pu, H., & Deng, M. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01188-6 · Cited by 23
The Role of Purinergic Receptors in Cancer-Induced Bone Pain
Falk, S., Uldall, M., & Heegaard, A. (2012) · Journal of Osteoporosis · doi:10.1155/2012/758181 · Cited by 23
“One of the complicating factors is the variation in expression pattern of various purinergic receptors on the nociceptors in different models, as described in the following sections.”
BackgroundYamashita, T., Kamikaseda, S., Tanaka, A., Tozaki‐Saitoh, H., Caaveiro, J. M. M., Inoue, K., & Tsuda, M. (2021) · Cells · doi:10.3390/cells10020434 · Cited by 23
“We next determined whether these three compounds affect the release of IL-1β from ATP-activated microglia that had been primed by lipopolysaccharide (LPS), a TLR4 agonist that is widely used to activate microglia and stimulate IL-1β release from spinal cord slices [32].”
BackgroundResultFranceschini, A., Hullugundi, S. K., van den Maagdenberg, A. M., Nistri, A., & Fabbretti, E. (2013) · Purinergic Signalling Purinergic Signalling · doi:10.1007/s11302-012-9328-1 · Cited by 26
“Since LPS can trigger ATP release [27, 28] that, in turn, stimulates TNFα synthesis and release [29] and further ATP release [30, 31], it seems plausible that, in R192Q KI cultures, LPS might have facilitated release of ATP that, via activation of hyper-responsive P2X3 receptors, could amplify nociceptive signaling, w…”
Reprint of: Microglial toll-like receptors and Alzheimer’s disease
Su, F., Bai, F., Zhou, H., & Zhang, Z. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.05.016 · Cited by 19
Teixeira, J. M., Dias, E. V., Parada, C. A., & Tambeli, C. H. (2016) · Journal of Pain · doi:10.1016/j.jpain.2016.10.008 · Cited by 20
Kwilasz, A. J., Green‐Fulgham, S. M., Duran-Malle, J. C., Schrama, A. E. W., Mitten, E. H., Todd, L. S., Patel, H. P., Larson, T. A., Clements, M. A., Harris, K. M., et al. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.12.016 · Cited by 20
REV-ERB activation as a novel pharmacological approach for treating inflammatory pain
Makhija, S., Griffett, J., Veerakanellore, G. B., Burris, T. P., Elgendy, B., & Griffett, K. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1171931 · Cited by 18
“As resident macrophages of the central nervous system (CNS), microglia have been implicated in the activation and sensation of pain in humans (Clark et al., 2010; Rhie et al., 2020; Ren and Illes, 2022).”
BackgroundBattilocchio, C., Guetzoyan, L. J., Cervetto, C., Mannelli, L. D. C., Frattaroli, D., Baxendale, I. R., Maura, G., Rossi, A., Sautebin, L., Biava, M., et al. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml400079h · Cited by 18
Metadata
- Authors
- Clark, A. K., Staniland, A. A., Marchand, F., Kaan, T. K. Y., McMahon, S. B., & Malcangio, M.
- Affiliations
- King's College London (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-01-13
- Volume
- 30
- Issue
- 2
- Pages
- 573-582
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2880485
- OpenAlex
- W2046299505
- Cited by
- 291
- References
- 62
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 14 · 2023: 11 · 2022: 13 · 2021: 17 · 2020: 18 · 2019: 9 · 2018: 9 · 2017: 18 · 2016: 21 · 2015: 28 · 2014: 22 · 2013: 25 · 2012: 26
- FWCI
- 20.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust (081553, 83259)
- Versus Arthritis
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- P2X7 receptor, IL-1β, lipopolysaccharide, nociception, spinal microglia, TLR4, dorsal horn, mechanical hyperalgesia, p38 MAPK, purinergic signaling, ATP, chronic pain
- MeSH terms
- Adenosine Triphosphate, Analysis of Variance, Animals, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Hyperalgesia, Lipopolysaccharides, Male, Pain Measurement, Phosphopyruvate Hydratase, Pyridines, Spinal Cord, Tetrazoles, Theophylline, Time Factors, Rats, Wistar, Pain Threshold, Microglia, Receptors, Purinergic P2, Mice, Knockout, Mitogen-Activated Protein Kinase 13, Mice, Rats, Interleukin-1beta, Receptors, Purinergic P2X7, Purinergic P2 Receptor Agonists, Purinergic P2 Receptor Antagonists, In Vitro Techniques
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
