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Microglie et récepteurs purinergiques P2X dans la douleur neuropathique : un duo excitateur inattendu

Microglia and purinergic P2X receptors in neuropathic pain: an unexpected excitatory duo

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Douleur et Analgésie

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Résumé

Les cellules microgliales représentent les macrophages résidents du système nerveux central. En réponse à une lésion des nerfs périphériques, les microglies spinales acquièrent un phénotype immunocompétent. La microglie peut « sentir » l’activité neuronale par le biais d’un répertoire important de récepteurs aux neurotransmetteurs. Parmi ceux-ci, les récepteurs purinergiques P2X, en induisant la sécrétion de molécules pro-inflammatoires, exacerbent l’excitabilité neuronale dans la corne dorsale de la moelle épinière et facilitent ainsi la genèse des douleurs neuropathiques.

Abstract

Microglia are brain resident macrophages. In response to peripheral nerve lesion, spinal cord microglia acquire an immunocompetent phenotype. Microglia can “sense” neuronal activity through an array of receptors for neurotransmitters. Among these, P2X purinergic receptors, by triggering the secretion of pro-inflammatory molecules, shape neuronal excitability in the dorsal horn of the spinal cord and thus promote neuropathic pain.

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Références

  1. Abbadie C, Lindia JA, Cumiskey AM, et al. (2003) Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc Natl Acad Sci USA 100: 7947–7952

    Article  PubMed  CAS  Google Scholar 

  2. Biber K, Neumann H, Inoue K, Boddeke HW (2007) Neuronal “On” and “Off” signals control microglia. Trends Neurosci 30: 596–602

    Article  PubMed  CAS  Google Scholar 

  3. Brough D, Le Feuvre RA, Iwakura Y, Rothwell NJ (2002) Purinergic (P2X7) receptor activation of microglia induces cell death via an interleukin-1-independent mechanism. Mol Cell Neurosci 19: 272–280

    Article  PubMed  CAS  Google Scholar 

  4. Burnstock G (2006) Historical review: ATP as a neurotransmitter. Trends Pharmacol Sci 27: 166–176

    Article  PubMed  CAS  Google Scholar 

  5. Chessell IP, Hatcher JP, Bountra C, et al. (2005) Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 114: 386–396

    Article  PubMed  CAS  Google Scholar 

  6. Collo G, Neidhart S, Kawashima E, et al. (1997) Tissue distribution of the P2X7 receptor. Neuropharmacology 36: 1277–1283

    Article  PubMed  CAS  Google Scholar 

  7. Coull JA, Boudreau D, Bachand K, et al. (2003) Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424: 938–942

    Article  PubMed  CAS  Google Scholar 

  8. Coull JA, Beggs S, Boudreau D, et al. (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438: 1017–1021

    Article  PubMed  CAS  Google Scholar 

  9. Coyle DE (1998) Partial peripheral nerve injury leads to activation of astroglia and microglia, which parallels the development of allodynic behavior. Glia 23: 75–83

    Article  PubMed  CAS  Google Scholar 

  10. Cuadros MA, Navascués J (1998) The origin and differentiation of microglial cells during development. Prog Neurobiol 56: 173–189

    Article  PubMed  CAS  Google Scholar 

  11. Davalos D, Grutzendler J, Yang G, et al. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8: 752–758

    Article  PubMed  CAS  Google Scholar 

  12. Egan TM, Khakh BS (2004) Contribution of calcium ions to P2X channel responses. J Neurosci 24: 3413–3420

    Article  PubMed  CAS  Google Scholar 

  13. Egan TM, Samways DS, Li Z (2006) Biophysics of P2X receptors. Pflugers Arch 452: 501–512

    Article  PubMed  CAS  Google Scholar 

  14. Farber K, Kettenmann H (2006) Purinergic signaling and microglia. Pflugers Arch 452: 615–621

    Article  PubMed  Google Scholar 

  15. Haynes SE, Hollopeter G, Yang G, et al. (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9: 1512–1519

    Article  PubMed  CAS  Google Scholar 

  16. Honda S, Sasaki Y, Ohsawa K, et al. (2001) Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J Neurosci 21: 1975–1982

    PubMed  CAS  Google Scholar 

  17. Honore P, Donnelly-Roberts D, Namovic MT, et al. (2006) A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino)methyl] amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat. J Pharmacol Exp Ther 319: 1376–1385

    Article  PubMed  CAS  Google Scholar 

  18. Jarvis MF, Burgard EC, McGaraughty S, et al. (2002) A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci USA 99: 17179–17184

    Article  PubMed  CAS  Google Scholar 

  19. Ji RR, Kawasaki Y, Zhuang ZY, Decosterd I (2006) Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway. Neuron Glia Biol 2: 259–269

    Article  PubMed  Google Scholar 

  20. McGeer PL McGeer EG (2002) Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve 26: 459–470

    Article  PubMed  CAS  Google Scholar 

  21. Milligan ED, Twining C, Chacur M, et al. (2003) Spinal glia and pro-inflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci 23: 1026–1040

    PubMed  CAS  Google Scholar 

  22. Moalem G, Tracey DJ (2006) Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 51: 240–264

    Article  PubMed  CAS  Google Scholar 

  23. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308: 1314–1318

    Article  PubMed  CAS  Google Scholar 

  24. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82: 1013–1067

    PubMed  CAS  Google Scholar 

  25. Pankratov Y, Lalo U, Verkhratsky A, North RA (2006) Vesicular release of ATP at central synapses. Pflugers Arch 452: 589–597

    Article  PubMed  CAS  Google Scholar 

  26. Pannasch U, Färber K, Nolte C, et al. (2006) The potassium channels Kv1.5 and Kv11.3 modulate distinct functions of microglia. Mol Cell Neurosci 33: 401–411

    Article  PubMed  CAS  Google Scholar 

  27. Rivera C, Voipio J, Thomas-Crusells J, et al. (2004) Mechanism of activity-dependent down regulation of the neuron-specific K-Cl cotransporter KCC2. J Neurosci 24: 4683–4691

    Article  PubMed  CAS  Google Scholar 

  28. Stence N, Waite M, Dailey ME (2001) Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices. Glia 33: 256–266

    Article  PubMed  CAS  Google Scholar 

  29. Streit WJ (2005) Microglia and neuroprotection: implications for Alzheimer’s disease. Brain Res Brain Res Rev 48: 234–239

    Article  PubMed  CAS  Google Scholar 

  30. Streit WJ, Conde JR, Fendrick SE, et al. (2005) Role of microglia in the central nervous system’s immune response. Neurol Res 27: 685–691

    PubMed  Google Scholar 

  31. Sweitzer S, Martin D, DeLeo JA (2001) Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain. Neuroscience 103: 529–539

    Article  PubMed  CAS  Google Scholar 

  32. Torres GE, Egan TM, Voigt MM (1999) Hetero-oligomeric assembly of P2X receptor subunits. Specificities exist with regard to possible partners. J Biol Chem 274: 6653–6659

    Article  PubMed  CAS  Google Scholar 

  33. Tsuda M, Mizokoshi A, Shigemoto-Mogami Y, et al. (2004) Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia 45: 89–95

    Article  PubMed  Google Scholar 

  34. Tsuda M, Shigemoto-Mogami Y, Koizumi S, et al. (2003) P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424: 778–783

    Article  PubMed  CAS  Google Scholar 

  35. Watkins LR, Maier SF (2002) Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 82: 981–1011

    PubMed  CAS  Google Scholar 

  36. Xu GY, Huang LY (2002) Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons. J Neurosci 22: 93–102

    PubMed  CAS  Google Scholar 

  37. Ziegler S, Schillinger M, Funk M, et al. (2005) Association of a functional polymorphism in the clopidogrel target receptor gene, P2Y12, and the risk for ischemic cerebrovascular events in patients with peripheral artery disease. Stroke 36: 1394–1399

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut de génomique fonctionnelle, CNRS UMR 5203, Inserm U661, université de Montpellier-I et II, 141, rue de la Cardonille, F-34090, Montpellier, France

    L. Ulmann & F. Rassendren

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  1. L. Ulmann
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  2. F. Rassendren
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Correspondence to L. Ulmann.

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Ulmann, L., Rassendren, F. Microglie et récepteurs purinergiques P2X dans la douleur neuropathique : un duo excitateur inattendu. Douleur analg 21, 221–226 (2008). https://doi.org/10.1007/s11724-008-0109-0

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  • DOI: https://doi.org/10.1007/s11724-008-0109-0

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