IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Glia as a Link between Neuroinflammation and Neuropathic Pain

  • Jha, Mithilesh Kumar (Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine) ;
  • Jeon, Sang-Min (Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine) ;
  • Suk, Kyoung-Ho (Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine)
  • Received : 2012.02.02
  • Accepted : 2012.02.17
  • Published : 2012.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Contemporary studies illustrate that peripheral injuries activate glial components of the peripheral and central cellular circuitry. The subsequent release of glial stressors or activating signals contributes to neuropathic pain and neuroinflammation. Recent studies document the importance of glia in the development and persistence of neuropathic pain and neuroinflammation as a connecting link, thereby focusing attention on the glial pathology as the general underlying factor in essentially all age-related neurodegenerative diseases. There is wide agreement that excessive glial activation is a key process in nervous system disorders involving the release of strong pro-inflammatory cytokines, which can trigger worsening of multiple disease states. This review will briefly discuss the recent findings that have shed light on the molecular and cellular mechanisms of glia as a connecting link between neuropathic pain and neuroinflammation.

Keywords

References

  1. Kriegstein A, Alvarez-Buylla A: The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32;149-184, 2009. https://doi.org/10.1146/annurev.neuro.051508.135600
  2. Moalem G, Tracey DJ: Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 51;240-264, 2006. https://doi.org/10.1016/j.brainresrev.2005.11.004
  3. Aamodt S: Focus on glia and disease. Nat Neurosci 10;1349, 2007. https://doi.org/10.1038/nn1107-1349
  4. Watkins LR, Milligan ED, Maier SF: Glial activation: a driving force for pathological pain. Trends Neurosci 24;450-455, 2001 https://doi.org/10.1016/S0166-2236(00)01854-3
  5. McMahon SB, Cafferty WB, Marchand F: Immune and glial cell factors as pain mediators and modulators. Exp Neurol 192;444-462, 2005. https://doi.org/10.1016/j.expneurol.2004.11.001
  6. Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438;1017-1021, 2005. https://doi.org/10.1038/nature04223
  7. Garrison CJ, Dougherty PM, Kajander KC, Carlton SM: Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res 565;1-7, 1991. https://doi.org/10.1016/0006-8993(91)91729-K
  8. Meller ST, Dykstra C, Grzybycki D, Murphy S, Gebhart GF: The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat. Neuropharmacology 33;1471-1478, 1994. https://doi.org/10.1016/0028-3908(94)90051-5
  9. Colburn RW, DeLeo JA, Rickman AJ, Yeager MP, Kwon P, Hickey WF: Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat. J Neuroimmunol 79;163-175, 1997. https://doi.org/10.1016/S0165-5728(97)00119-7
  10. Milligan ED, Mehmert KK, Hinde JL, Harvey LO, Martin D, Tracey KJ, Maier SF, Watkins LR: Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120. Brain Res 861;105-116, 2000. https://doi.org/10.1016/S0006-8993(00)02050-3
  11. Chacur M, Milligan ED, Gazda LS, Armstrong C, Wang H, Tracey KJ, Maier SF, Watkins LR: A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats. Pain 94;231-244, 2001. https://doi.org/10.1016/S0304-3959(01)00354-2
  12. Raghavendra V, Tanga FY, DeLeo JA: Complete Freunds adjuvant- induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci 20;467-473, 2004. https://doi.org/10.1111/j.1460-9568.2004.03514.x
  13. Möller T: Neuroinflammation in Huntington's disease. J Neural Transm 117;1001-1008, 2010. https://doi.org/10.1007/s00702-010-0430-7
  14. Björkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, Raibon E, Lee RV, Benn CL, Soulet D, Magnusson A, Woodman B, Landles C, Pouladi MA, Hayden MR, Khalili- Shirazi A, Lowdell MW, Brundin P, Bates GP, Leavitt BR, Möller T, Tabrizi SJ: A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J Exp Med 205;1869-1877, 2008. https://doi.org/10.1084/jem.20080178
  15. Garden GA, Möller T: Microglia biology in health and disease. J Neuroimmune Pharmacol 1;127-137, 2006. https://doi.org/10.1007/s11481-006-9015-5
  16. Weydt P, Möller T: Neuroinflammation in the pathogenesis of amyotrophic lateral sclerosis. Neuroreport 16;527-531, 2005. https://doi.org/10.1097/00001756-200504250-00001
  17. Block ML, Hong JS: Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76;77-98, 2005. https://doi.org/10.1016/j.pneurobio.2005.06.004
  18. Mrak RE, Griffin WS: Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol Aging 22;903-908, 2001. https://doi.org/10.1016/S0197-4580(01)00287-1
  19. Phillis JW, Horrocks LA, Farooqui AA: Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders. Brain Res Rev 52;201-243, 2006. https://doi.org/10.1016/j.brainresrev.2006.02.002
  20. Sriram K, O'Callaghan JP: Divergent roles for tumor necrosis factor-alpha in the brain. J Neuroimmune Pharmacol2;140-153, 2007. https://doi.org/10.1007/s11481-007-9070-6
  21. Ubogu EE, Cossoy MB, Ransohoff RM: The expression and function of chemokines involved in CNS inflammation. Trends Pharmacol Sci 27;48-55, 2006. https://doi.org/10.1016/j.tips.2005.11.002
  22. Weed DL: The merger of bioethics and epidemiology. J Clin Epidemiol 44 Suppl 1;15S-22S, 1991.
  23. Baptista MJ, Cookson MR, Miller DW: Parkin and alpha-synuclein: opponent actions in the pathogenesis of Parkinson's disease. Neuroscientist 10;63-72, 2004. https://doi.org/10.1177/1073858403260392
  24. Gilron I, Watson CP, Cahill CM, Moulin DE: Neuropathic pain: a practical guide for the clinician. CMAJ 175;265-275,2006. https://doi.org/10.1503/cmaj.060146
  25. Kielian T: Microglia and chemokines in infectious diseases of the nervous system: views and reviews. Front Biosci 9;732-750, 2004. https://doi.org/10.2741/1266
  26. Ransohoff RM, Glabinski A, Tani M: Chemokines in immune- mediated inflammation of the central nervous system. Cytokine Growth Factor Rev 7;35-46, 1996. https://doi.org/10.1016/1359-6101(96)00003-2
  27. Cartier L, Hartley O, Dubois-Dauphin M, Krause KH: Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48;16-42, 2005. https://doi.org/10.1016/j.brainresrev.2004.07.021
  28. Kreutzberg GW: Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19;312-318, 1996. https://doi.org/10.1016/0166-2236(96)10049-7
  29. Clayton DF, George JM: Synucleins in synaptic plasticity and neurodegenerative disorders. J Neurosci Res 58;120-129,1999. https://doi.org/10.1002/(SICI)1097-4547(19991001)58:1<120::AID-JNR12>3.0.CO;2-E
  30. Becher B, Prat A, Antel JP: Brain-immune connection: immuno- regulatory properties of CNS-resident cells. Glia 29;293-304, 2000. https://doi.org/10.1002/(SICI)1098-1136(20000215)29:4<293::AID-GLIA1>3.0.CO;2-A
  31. Scholz J, Woolf CJ: The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10;1361-1368, 2007. https://doi.org/10.1038/nn1992
  32. Halassa MM, Fellin T, Haydon PG: The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med 13;54-63, 2007. https://doi.org/10.1016/j.molmed.2006.12.005
  33. Pocock JM, Kettenmann H: Neurotransmitter receptors on microglia. Trends Neurosci 30;527-535, 2007. https://doi.org/10.1016/j.tins.2007.07.007
  34. Watkins LR, Wieseler-Frank J, Milligan ED, Johnston I, Maier SF: Chapter 22 Contribution of glia to pain processing in health and disease. Handb Clin Neurol 81;309-323, 2006.
  35. Gwak YS, Kang J, Unabia GC, Hulsebosch CE: Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp Neurol 234;362-372, 2012. https://doi.org/10.1016/j.expneurol.2011.10.010
  36. Julius D, Basbaum AI: Molecular mechanisms of nociception. Nature 413;203-210, 2001. https://doi.org/10.1038/35093019
  37. Scholz J, Woolf CJ: Can we conquer pain? Nat Neurosci 5 Suppl;1062-1067, 2002. https://doi.org/10.1038/nn942
  38. Block ML, Zecca L, Hong JS: Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8;57-69, 2007. https://doi.org/10.1038/nrn2038
  39. Lobsiger CS, Cleveland DW: Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease. Nat Neurosci 10;1355-1360, 2007. https://doi.org/10.1038/nn1988
  40. Vallejo R, Tilley DM, Vogel L, Benyamin R: The role of glia and the immune system in the development and maintenance of neuropathic pain. Pain Pract 10;167-184, 2010. https://doi.org/10.1111/j.1533-2500.2010.00367.x
  41. Colburn RW, Rickman AJ, DeLeo JA: The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp Neurol 157;289-304, 1999. https://doi.org/10.1006/exnr.1999.7065
  42. Raghavendra V, Tanga F, DeLeo JA: Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 306;624-630, 2003. https://doi.org/10.1124/jpet.103.052407
  43. Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, Watkins LR: Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 115;71-83, 2005. https://doi.org/10.1016/j.pain.2005.02.009
  44. DeLeo JA, Winkelstein BA: Physiology of chronic spinal pain syndromes: from animal models to biomechanics. Spine (Phila Pa 1976) 27;2526-2537, 2002. https://doi.org/10.1097/00007632-200211150-00026
  45. Watkins LR, Hutchinson MR, Milligan ED, Maier SF: "Listening" and "talking" to neurons: implications of immune activation for pain control and increasing the efficacy of opioids. Brain Res Rev 56;48-69, 2007.
  46. Wieseler-Frank J, Maier SF, Watkins LR: Glial activation and pathological pain. Neurochem Int 45;389-395, 2004. https://doi.org/10.1016/j.neuint.2003.09.009
  47. Ji RR, Suter MR: p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 3;33, 2007. https://doi.org/10.1186/1744-8069-3-33
  48. Zhuang ZY, Gerner P, Woolf CJ, Ji RR: ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 114;149-159, 2005. https://doi.org/10.1016/j.pain.2004.12.022
  49. Dubuisson D, Dennis SG: The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 4;161-174, 1977. https://doi.org/10.1016/0304-3959(77)90130-0
  50. Abbott FV, Franklin KB, Westbrook RF: The formalin test: scoring properties of the first and second phases of the pain response in rats. Pain 60;91-102, 1995. https://doi.org/10.1016/0304-3959(94)00095-V
  51. Puig S, Sorkin LS: Formalin-evoked activity in identified primary afferent fibers: systemic lidocaine suppresses phase-2 activity. Pain 64;345-355, 1996. https://doi.org/10.1016/0304-3959(95)00121-2
  52. Tjølsen A, Berge OG, Hunskaar S, Rosland JH, Hole K: The formalin test: an evaluation of the method. Pain 51;5-17,1992. https://doi.org/10.1016/0304-3959(92)90003-T
  53. Colpaert FC: Evidence that adjuvant arthritis in the rat is associated with chronic pain. Pain 28;201-222, 1987. https://doi.org/10.1016/0304-3959(87)90117-5
  54. Millan MJ, Członkowski A, Morris B, Stein C, Arendt R, Huber A, Höllt V, Herz A: Inflammation of the hind limb as a model of unilateral, localized pain: influence on multiple opioid systems in the spinal cord of the rat. Pain 35;299-312, 1988. https://doi.org/10.1016/0304-3959(88)90140-6
  55. Iadarola MJ, Brady LS, Draisci G, Dubner R: Enhancement of dynorphin gene expression in spinal cord following experimental inflammation: stimulus specificity, behavioral parameters and opioid receptor binding. Pain 35;313-326, 1988. https://doi.org/10.1016/0304-3959(88)90141-8
  56. Lao L, Zhang RX, Zhang G, Wang X, Berman BM, Ren K: A parametric study of electroacupuncture on persistent hyperalgesia and Fos protein expression in rats. Brain Res1020;18-29, 2004. https://doi.org/10.1016/j.brainres.2004.01.092
  57. Li K, Lin T, Cao Y, Light AR, Fu KY: Peripheral formalin injury induces 2 stages of microglial activation in the spinal cord. J Pain 11;1056-1065, 2010. https://doi.org/10.1016/j.jpain.2010.01.268
  58. Lin T, Li K, Zhang FY, Zhang ZK, Light AR, Fu KY: Dissociation of spinal microglia morphological activation and peripheral inflammation in inflammatory pain models. J Neuroimmunol 192;40-48, 2007. https://doi.org/10.1016/j.jneuroim.2007.09.003
  59. Ren K, Dubner R: Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol 21;570-579,2008. https://doi.org/10.1097/ACO.0b013e32830edbdf
  60. Gao YJ, Ji RR: Targeting astrocyte signaling for chronic pain. Neurotherapeutics 7;482-493, 2010. https://doi.org/10.1016/j.nurt.2010.05.016
  61. Watkins LR, Hutchinson MR, Ledeboer A, Wieseler-Frank J, Milligan ED, Maier SF: Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids. Brain Behav Immun 21;131-146, 2007. https://doi.org/10.1016/j.bbi.2006.10.011

Cited by

  1. Glia and Mast Cells as Targets for Palmitoylethanolamide, an Anti-inflammatory and Neuroprotective Lipid Mediator vol.48, pp.2, 2012, https://doi.org/10.1007/s12035-013-8487-6
  2. Inflaming the Brain: CRPS a Model Disease to Understand Neuroimmune Interactions in Chronic Pain vol.8, pp.3, 2012, https://doi.org/10.1007/s11481-012-9422-8
  3. Use of Natural Compounds in the Management of Diabetic Peripheral Neuropathy vol.19, pp.3, 2012, https://doi.org/10.3390/molecules19032877
  4. Flexibilide Obtained from Cultured Soft Coral Has Anti-Neuroinflammatory and Analgesic Effects through the Upregulation of Spinal Transforming Growth Factor-β1 in Neuropathic Rats vol.12, pp.7, 2012, https://doi.org/10.3390/md12073792
  5. Analgesic effects of naringenin in rats with spinal nerve ligation-induced neuropathic pain vol.2, pp.4, 2012, https://doi.org/10.3892/br.2014.267
  6. Inhibition of the spinal astrocytic JNK/MCP-1 pathway activation correlates with the analgesic effects of tanshinone IIA sulfonate in neuropathic pain vol.12, pp.None, 2012, https://doi.org/10.1186/s12974-015-0279-7
  7. Effect of Epac1 on pERK and VEGF Activation in Postoperative Persistent Pain in Rats vol.59, pp.4, 2012, https://doi.org/10.1007/s12031-016-0776-x
  8. Plasma pro-inflammatory markers in chronic neuropathic pain: A multivariate, comparative, cross-sectional pilot study vol.10, pp.1, 2016, https://doi.org/10.1016/j.sjpain.2015.06.006
  9. Safflower Yellow regulates microglial polarization and inhibits inflammatory response in LPS-stimulated Bv2 cells vol.29, pp.1, 2012, https://doi.org/10.1177/0394632015617065
  10. A novel role for protein tyrosine phosphatase 1B as a positive regulator of neuroinflammation vol.13, pp.None, 2012, https://doi.org/10.1186/s12974-016-0545-3
  11. Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models vol.13, pp.None, 2016, https://doi.org/10.1186/s12974-016-0696-2
  12. Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain vol.2017, pp.None, 2012, https://doi.org/10.1155/2017/7346103
  13. Etanercept attenuates thermal and mechanical hyperalgesia induced by bone cancer vol.13, pp.5, 2017, https://doi.org/10.3892/etm.2017.4260
  14. Picroside II Attenuates CCI-Induced Neuropathic Pain in Rats by Inhibiting Spinal Reactive Astrocyte-Mediated Neuroinflammation Through the NF-κB Pathway vol.43, pp.5, 2012, https://doi.org/10.1007/s11064-018-2518-7
  15. Neuroprotective effects of silibinin: an in silico and in vitro study vol.128, pp.10, 2012, https://doi.org/10.1080/00207454.2018.1443926
  16. Lappaconitine, a C18-diterpenoid alkaloid, exhibits antihypersensitivity in chronic pain through stimulation of spinal dynorphin A expression vol.235, pp.9, 2018, https://doi.org/10.1007/s00213-018-4948-y
  17. MC4R Is Involved in Neuropathic Pain by Regulating JNK Signaling Pathway After Chronic Constriction Injury vol.13, pp.None, 2012, https://doi.org/10.3389/fnins.2019.00919
  18. Gallic and vanillic acid suppress inflammation and promote myelination in an in vitro mouse model of neurodegeneration vol.46, pp.1, 2012, https://doi.org/10.1007/s11033-018-4557-1
  19. Ferulic Acid Rescues LPS-Induced Neurotoxicity via Modulation of the TLR4 Receptor in the Mouse Hippocampus vol.56, pp.4, 2012, https://doi.org/10.1007/s12035-018-1280-9
  20. Microglia-Astrocyte Crosstalk: An Intimate Molecular Conversation vol.25, pp.3, 2019, https://doi.org/10.1177/1073858418783959
  21. Aspirin up‐regulates suppressor of cytokine signaling 3 in glial cells via PPARα vol.151, pp.1, 2012, https://doi.org/10.1111/jnc.14813
  22. Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice vol.11, pp.12, 2012, https://doi.org/10.3390/toxins11120679
  23. Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB vol.33, pp.1, 2012, https://doi.org/10.3344/kjp.2020.33.1.30
  24. Cholinergic Modulation of Glial Function During Aging and Chronic Neuroinflammation vol.14, pp.None, 2012, https://doi.org/10.3389/fncel.2020.577912
  25. Neuroglial Cells Activation and Inflammatory Factors Increase by Lipopolysaccharide Treatment in Adult Mouse Hippocampus vol.54, pp.1, 2012, https://doi.org/10.14397/jals.2020.54.1.61
  26. Minocycline reduces experimental muscle hyperalgesia induced by repeated nerve growth factor injections in humans: A placebo‐controlled double‐blind drug‐crossover study vol.24, pp.6, 2012, https://doi.org/10.1002/ejp.1558
  27. Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats vol.79, pp.12, 2012, https://doi.org/10.1093/jnen/nlaa127
  28. Minocycline for Controlling Neuropathic Pain: A Systematic Narrative Review of Studies in Humans vol.14, pp.None, 2012, https://doi.org/10.2147/jpr.s292824
  29. Upregulation of IL-1 Receptor Antagonist by Aspirin in Glial Cells via Peroxisome Proliferator-Activated Receptor-Alpha vol.5, pp.1, 2012, https://doi.org/10.3233/adr-210026
  30. Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-κB pathway vol.25, pp.3, 2021, https://doi.org/10.4196/kjpp.2021.25.3.217
  31. Novel Applications of NSAIDs: Insight and Future Perspectives in Cardiovascular, Neurodegenerative, Diabetes and Cancer Disease Therapy vol.22, pp.12, 2012, https://doi.org/10.3390/ijms22126637
  32. Molecular mechanisms of opioid tolerance: From opioid receptors to inflammatory mediators (Review) vol.22, pp.3, 2012, https://doi.org/10.3892/etm.2021.10437
  33. Interaction of Opioids with TLR4-Mechanisms and Ramifications vol.13, pp.21, 2012, https://doi.org/10.3390/cancers13215274