The purinergic system and glial cells: Emerging costars in nociception

BioMed Research International

Volumn 2014, Issue , 2014, Pages

  Magni, Giulia ^a,b   Ceruti, Stefania ^a,c  

^a UNIVERSITY OF MILAN   (Italy)

^b ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^c NONE

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE A1 RECEPTOR; ADENOSINE A2A RECEPTOR; ADENOSINE A2B RECEPTOR; ANALGESIC AGENT; BRAIN DERIVED NEUROTROPHIC FACTOR; CATHEPSIN S; G PROTEIN COUPLED RECEPTOR; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; NEUROTRANSMITTER; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PURINERGIC P2X1 RECEPTOR; PURINERGIC P2X2 RECEPTOR; PURINERGIC P2X3 RECEPTOR; PURINERGIC P2X4 RECEPTOR; PURINERGIC P2X5 RECEPTOR; PURINERGIC P2X6 RECEPTOR; PURINERGIC P2X7 RECEPTOR; PURINERGIC P2Y1 RECEPTOR; PURINERGIC P2Y12 RECEPTOR; PURINERGIC P2Y13 RECEPTOR; PURINERGIC P2Y2 RECEPTOR; PURINERGIC P2Y4 RECEPTOR; PURINERGIC P2Y6 RECEPTOR; PURINERGIC RECEPTOR; UNINDEXED DRUG;

ALLODYNIA; ASTROCYTE; CELL COMMUNICATION; CELLULAR DISTRIBUTION; CHRONIC PAIN; DORSAL ROOT; DORSAL ROOT GANGLIA; DOWN REGULATION; GANGLION; GLIA CELL; HYPERALGESIA; IMMUNOFLUORESCENCE; MICROGLIA; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; PHAGOCYTOSIS; RECEPTOR UPREGULATION; REVIEW; SENSORY GANGLION; SENSORY NERVE CELL; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SPINAL CORD; TRIGEMINAL NERVE; TRIGEMINUS GANGLION; ANIMAL; DRUG EFFECTS; GLIA; HUMAN; METABOLISM; NERVE CELL; PATHOPHYSIOLOGY;

ANALGESICS; ANIMALS; CHRONIC PAIN; HUMANS; NEUROGLIA; NEURONS; NOCICEPTION; RECEPTORS, PURINERGIC;

EID: 84921847665     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2014/495789     Document Type: Review

References (118)

1. C. J. Woolf and M. W. Salter, "Neuronal plasticity: increasing the gain in pain, " Science, vol. 288, no. 5472, pp. 1765-1768, 2000.
2. F. Xu, Y. Li, S. Li et al. , "Complete Freund's adjuvant-induced acute inflammatory pain could be attenuated by triptolide via inhibiting spinal glia activation in rats, " Journal of Surgical Research, vol. 188, pp. 174-182, 2014.
3. R. Ji, T. Berta, and M. Nedergaard, "Glia and pain: is chronic pain a gliopathy?" Pain, vol. 154, supplement 1, pp. S10-S28, 2013.
4. M. Tsuda, K. Inoue, and M. W. Salter, "Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia, " Trends in Neurosciences, vol. 28, no. 2, pp. 101-107, 2005.
5. M. R. Suter, Y. Wen, I. Decosterd, andR. Ji, "Doglial cells control pain?" Neuron Glia Biology, vol. 3, no. 3, pp. 255-268, 2007.
6. I. Kazuhide and T. Makoto, "Microglia and neuropathic pain, " Glia, vol. 57, no. 14, pp. 1469-1479, 2009.
7. K. Inoue, "ATP receptors of microglia involved in pain, " Novartis Foundation Symposium, vol. 276, pp. 263-272, 2006.
8. V. Tiwari, Y. Guan, and S. N. Raja, "Modulating the delicate glial-neuronal interactions in neuropathic pain: promises and potential caveats, " Neuroscience & Biobehavioral Reviews, vol. 45, pp. 19-27, 2014.
9. A. Buffo, C. Rolando, and S. Ceruti, "Astrocytes in the damaged brain: molecular and cellular insights into their reactive response and healing potential, " Biochemical Pharmacology, vol. 79, no. 2, pp. 77-89, 2010.
10. M. Hanani, "Satellite glial cells in sympathetic and parasympathetic ganglia: in search of function, " Brain Research Reviews, vol. 64, no. 2, pp. 304-327, 2010.
11. M. Takeda, T. Tanimoto, J. Kadoi et al. , "Enhanced excitability of nociceptive trigeminal ganglion neurons by satellite glial cytokine following peripheral inflammation, " Pain, vol. 129, no. 1-2, pp. 155-166, 2007.
12. X. Zhang, Y. Chen, C. Wang, and L.-Y. M. Huang, "Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia, " Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 23, pp. 9864-9869, 2007.
13. M. Ledda, E. Blum, S. de Palo, andM. Hanani, "Augmentation in gap junction-mediated cell coupling in dorsal root ganglia following sciatic nerve neuritis in the mouse, " Neuroscience, vol. 164, no. 4, pp. 1538-1545, 2009.
14. G. Villa, S. Ceruti, M. Zanardelli et al. , "Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus, " Molecular Pain, vol. 6, article 89, 2010.
15. M. Donegan, M. Kernisant, C. Cua et al. , "Satellite glial cell proliferation in the trigeminal ganglia after chronic constriction injury of the infraorbital nerve, " Glia, vol. 61, pp. 2000-2008, 2013.
16. M. P. Abbracchio, G. Burnstock, A. Verkhratsky, and H. Zimmermann, "Purinergic signalling in the nervous system: an overview, " Trends inNeurosciences, vol. 32, no. 1, pp. 19-29, 2009.
17. G. Burnstock, U. Krügel, M. P. Abbracchio, and P. Illes, "Purinergic signalling: from normal behaviour to pathological brain function, " Progress in Neurobiology, vol. 95, no. 2, pp. 229-274, 2011.
18. R. A. North and M. F. Jarvis, "P2X receptors as drug targets, " Molecular Pharmacology, vol. 83, no. 4, pp. 759-769, 2013.
19. V. Khmyz, O. Maximyuk, V. Teslenko, A. Verkhratsky, and O. Krishtal, "P2X3 receptor gating near normal body temperature, " Pflugers Archiv European Journal of Physiology, vol. 456, no. 2, pp. 339-347, 2008.
20. S. P. H. Alexander, H. E. Benson, E. Faccenda et al. , "The concise guide to PHARMACOLOGY 2013/14: ligand-gated ion channels, " British Journal of Pharmacology, vol. 170, no. 8, pp. 1582-1606, 2013.
21. T. Bleehen and C. A. Keele, "Observations on the algogenic actions of adenosine compounds on the human blister base preparation, " Pain, vol. 3, no. 4, pp. 367-377, 1977.
22. P. M. Dunn, Y. Zhong, and G. Burnstock, "P2X receptors in peripheral neurons, " Progress in Neurobiology, vol. 65, no. 2, pp. 107-134, 2001.
23. Y. S. Kim, S. K. Paik, Y. S. Cho et al. , "Expression of P2X3 receptor in the trigeminal sensory nuclei of the rat, " Journal of Comparative Neurology, vol. 506, no. 4, pp. 627-639, 2008.
24. G. Burnstock, "Purines and sensory nerves, " Handbook of Experimental Pharmacology, vol. 194, pp. 333-392, 2009.
25. J. H. Cho, K. Y. Jung, Y. Jung et al. , "Design and synthesis of potent and selective P2X3 receptor antagonists derived from PPADS as potential pain modulators, " European Journal of Medicinal Chemistry, vol. 70, pp. 811-830, 2013.
26. C. C. Chen, A. N. Akopian, L. Sivilotti, D. Colquhoun, G. Burnstock, and J. N. Wood, "A P2X purinoceptor expressed by a subset of sensory neurons, " Nature, vol. 377, no. 6548, pp. 428-431, 1995.
27. R. A. North, "P2X3 receptors and peripheral painmechanisms, " The Journal of Physiology, vol. 554, no. 2, pp. 301-308, 2004.
28. S. Ceruti, M. Fumagalli, G. Villa, C. Verderio, and M. P. Abbracchio, "Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures, " Cell Calcium, vol. 43, no. 6, pp. 576-590, 2008.
29. S. K. Hullugundi, M. D. Ferrari, A. M. J. M. van den Maagdenberg, and A. Nistri, "The mechanism of functional upregulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine type 1 (FHM-1), " PLoS ONE, vol. 8, no. 4, Article ID e60677, 2013.
30. I. J. Llewellyn-Smith and G. Burnstock, "Ultrastructural localization of P2X3 receptors in rat sensory neurons, " NeuroReport, vol. 9, no. 11, pp. 2545-2550, 1998.
31. M. Tsuda, S. Koizumi, A. Kita, Y. Shigemoto, S. Ueno, and K. Inoue, "Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin-insensitive primary afferent neurons, " Journal of Neuroscience, vol. 20, no. 15, article RC90, 2000.
32. Y. Chen, G. W. Li, C. Wang, Y. Gu, and L. M. Huang, "Mechanisms underlying enhanced P2X receptor-mediated responses in the neuropathic pain state, " Pain, vol. 119, no. 1-3, pp. 38-48, 2005.
33. K. Kage, W. Niforatos, C. Z. Zhu, K. J. Lynch, P. Honore, and M. F. Jarvis, "Alteration of dorsal root ganglion P2X3 receptor expression and function following spinal nerve ligation in the rat, " Experimental Brain Research, vol. 147, no. 4, pp. 511-519, 2002.
34. R. D. Cheng, W. Z. Tu, W. S. Wang et al. , "Effect of electroacupuncture on the pathomorphology of the sciatic nerve and the sensitization of P2X3 receptors in the dorsal root ganglion in rats with chronic constrictive injury, " Chinese Journal of Integrative Medicine, vol. 19, no. 5, pp. 374-379, 2013.
35. J. Barclay, S. Patel, G. Dorn et al. , "Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain, " The Journal of Neuroscience, vol. 22, no. 18, pp. 8139-8147, 2002.
36. P. Honore, J. Mikusa, B. Bianchi et al. , "TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics, " Pain, vol. 96, no. 1-2, pp. 99-105, 2002.
37. A. P. Ford, "In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization, " Purinergic Signalling, vol. 8, no. 1, pp. 3-26, 2012.
38. A. M. W. Taylor and A. Ribeiro-da-Silva, "GDNF levels in the lower lip skin in a rat model of trigeminal neuropathic pain: implications for nonpeptidergic fiber reinnervation and parasympathetic sprouting, " Pain, vol. 152, no. 7, pp. 1502-1510, 2011.
39. T. Hautaniemi, N. Petrenko, A. Skorinkin, and R. Giniatullin, "The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons, " Neuroscience, vol. 209, pp. 32-38, 2012.
40. S. Liang, C. Xu, G. Li, and Y. Gao, "P2X receptors and modulation of pain transmission: focus on effects of drugs and compounds used in traditional Chinesemedicine, " Neurochemistry International, vol. 57, no. 7, pp. 705-712, 2010.
41. J. A. M. Coull, S. Beggs, D. Boudreau et al. , "BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain, " Nature, vol. 438, no. 7070, pp. 1017-1021, 2005.
42. M. F. Jarvis, "The neural-glial purinergic receptor ensemble in chronic pain states, " Trends in Neurosciences, vol. 33, no. 1, pp. 48-57, 2010.
43. M. Maeda, M. Tsuda, H. Tozaki-Saitoh, K. Inoue, and H. Kiyama, "Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn, " Gila, vol. 58, no. 15, pp. 1838-1846, 2010.
44. T. Trang, S. Beggs, and M. W. Salter, "ATP receptors gate microglia signaling in neuropathic pain, " Experimental Neurology, vol. 234, no. 2, pp. 354-361, 2012.
45. T. Trang, S. Beggs, and M. W. Salter, "Brain-derived neurotrophic factor from microglia: a molecular substrate for neuropathic pain, " Neuron Glia Biology, vol. 7, no. 1, pp. 99-108, 2012.
46. M. R. Bianco, G. Cirillo, V. Petrosino et al. , "Neuropathic pain and reactive gliosis are reversed by dialdehydic compound in neuropathic pain ratmodels, " Neuroscience Letters, vol. 530, no. 1, pp. 85-90, 2012.
47. M. Tsuda, Y. Shigemoto-Mogami, S. Koizumi et al. , "P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury, " Nature, vol. 424, no. 6950, pp. 778-783, 2003.
48. L. Ulmann, J. P. Hatcher, J. P. Hughes et al. , "Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain, " Journal of Neuroscience, vol. 28, no. 44, pp. 11263-11268, 2008.
49. M. Tsuda, E. Toyomitsu, T. Komatsu et al. , "Fibronectin/integrin system is involved in P2X(4) receptor upregulation in the spinal cord and neuropathic pain after nerve injury, " Glia, vol. 56, no. 5, pp. 579-585, 2008.
50. K. Biber, M. Tsuda, H. Tozaki-Saitoh et al. , "Neuronal CCL21 up-regulates microglia P2X4 expression and initiates neuropathic pain development, " EMBO Journal, vol. 30, no. 9, pp. 1864-1873, 2011.
51. M. Tsuda, T. Masuda, J. Kitano, H. Shimoyama, H. Tozaki-Saitoh, and K. Inoue, "IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain, " Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 19, pp. 8032-8037, 2009.
52. H. Yuan, X. Zhu, S. Zhou et al. , "Role of mast cell activation in inducing microglial cells to release neurotrophin, " Journal of Neuroscience Research, vol. 88, no. 6, pp. 1348-1354, 2010.
53. K. Nasu-Tada, S. Koizumi, M. Tsuda, E. Kunifusa, and K. Inoue, "Possible involvement of increase in spinal fibronectin following peripheral nerve injury in upregulation of microglial P2X4, a key molecule for mechanical allodynia, " Glia, vol. 53, no. 7, pp. 769-775, 2006.
54. M. Tsuda, H. Tozaki-Saitoh, T. Masuda et al. , "Lyn tyrosine kinase is required for P2X4 receptor upregulation and neuropathic pain after peripheral nerve injury, " GLIA, vol. 56, no. 1, pp. 50-58, 2008.
55. T. Trang, S. Beggs, X. Wan, and M. W. Salter, "P2X4-receptormediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogenactivated protein kinase activation, " Journal ofNeuroscience, vol. 29, no. 11, pp. 3518-3528, 2009.
56. S. Beggs, T. Trang, and M. W. Salter, "P2X4R + microglia drive neuropathic pain, " Nature Neuroscience, vol. 15, no. 8, pp. 1068-1073, 2012.
57. R. A. North, "Molecular physiology of P2X receptors, " Physiological Reviews, vol. 82, no. 4, pp. 1013-1067, 2002.
58. M. Monif, G. Burnstock, and D. A. Williams, "Microglia: proliferation and activation driven by the P2X7 receptor, " International Journal of Biochemistry and Cell Biology, vol. 42, no. 11, pp. 1753-1756, 2010.
59. A. K. Clark, A. A. Staniland, F. Marchand, T. K. Y. Kaan, S. B. McMahon, and M. Malcangio, "P2X7-dependent release of interleukin-1β and nociception in the spinal cord following lipopolysaccharide, " Journal of Neuroscience, vol. 30, no. 2, pp. 573-582, 2010.
60. A. K. Clark, R. Wodarski, F. Guida, O. Sasso, andM. Malcangio, "Cathepsin S release from primary cultured microglia is regulated by the P2X7 receptor, " Glia, vol. 58, no. 14, pp. 1710-1726, 2010.
61. I. P. Chessell, J. P. Hatcher, C. Bountra et al. , "Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain, " Pain, vol. 114, no. 3, pp. 386-396, 2005.
62. S. McGaraughty, K. L. Chu, M. T. Namovic et al. , "P2X7-related modulation of pathological nociception in rats, " Neuroscience, vol. 146, no. 4, pp. 1817-1828, 2007.
63. A. Perez-Medrano, D. L. Donnelly-Roberts, P. Honore et al. , "Discovery and biological evaluation of novel cyanoguanidine P2X7 antagonists with analgesic activity in a rat model of neuropathic pain, " Journal of Medicinal Chemistry, vol. 52, no. 10, pp. 3366-3376, 2009.
64. W. He, J. Cui, L. Du et al. , "Spinal P2X 7 receptor mediates microglia activation-induced neuropathic pain in the sciatic nerve injury rat model, " Behavioural Brain Research, vol. 226, no. 1, pp. 163-170, 2012.
65. R. E. Sorge, T. Trang, R. Dorfman et al. , "Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity, " Nature Medicine, vol. 18, no. 4, pp. 595-599, 2012.
66. G. Ito, Y. Suekawa, M. Watanabe et al. , "P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury, " European Journal of Pain, vol. 17, no. 2, pp. 185-199, 2013.
67. C. Guo, M. Masin, O. S. Qureshi, and R. D. Murrell-Lagnado, "Evidence for functional P2X4/P2X7 heteromeric receptors, " Molecular Pharmacology, vol. 72, no. 6, pp. 1447-1456, 2007.
68. G. Dell'Antonio, A. Quattrini, E. Dal Cin, A. Fulgenzi, and M. E. Ferrero, "Antinociceptive effect of a new P2Z/P2X7 antagonist, oxidizedATP, in arthritic rats, "Neuroscience Letters, vol. 327, no. 2, pp. 87-90, 2002.
69. A. Wahlert, L. Funkelstein, B. Fitzsimmons, T. Yaksh, and V. Hook, "Spinal astrocytes produce and secrete dynorphin neuropeptides, " Neuropeptides, vol. 47, no. 2, pp. 109-115, 2013.
70. Y. Chen, X. Zhang, C. Wang, G. Li, Y. Gu, and L. M. Huang, "Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons, " Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 43, pp. 16773-16778, 2008.
71. R. Kushnir, P. S. Cherkas, and M. Hanani, "Peripheral inflammation upregulates P2X receptor expression in satellite glial cells of mouse trigeminal ganglia: a calcium imaging study, " Neuropharmacology, vol. 61, no. 4, pp. 739-746, 2011.
72. T. C. Stock, B. J. Bloom, N. Wei et al. , "Efficacy and safety of CE-224, 535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate, " Journal of Rheumatology, vol. 39, no. 4, pp. 720-727, 2012.
73. E. C. Keystone, M. M. Wang, M. Layton, S. Hollis, and I. B. McInnes, "Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patientswith active disease despite treatment with methotrexate or sulphasalazine, " Annals of the Rheumatic Diseases, vol. 71, no. 10, pp. 1630-1635, 2012.
74. Z. Ali, B. Laurijssens, T. Ostenfeld et al. , "Pharmacokinetic and pharmacodynamic profiling of a P2X7 receptor allosteric modulator GSK1482160 in healthy human subjects, " British Journal of Clinical Pharmacology, vol. 75, no. 1, pp. 197-207, 2013.
75. G. Magni and S. Ceruti, "P2Y purinergic receptors: new targets for analgesic and antimigraine drugs, " Biochemical Pharmacology, vol. 85, no. 4, pp. 466-477, 2013.
76. K. D. Lustig, A. K. Shiau, A. J. Brake, andD. Julius, "Expression cloning of an ATP receptor from mouse neuroblastoma cells, " Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 11, pp. 5113-5117, 1993.
77. T. E. Webb, J. Simon, B. J. Krishek et al. , "Cloning and functional expression of a brain G-protein-coupled ATP receptor, " FEBS Letters, vol. 324, no. 2, pp. 219-225, 1993.
78. M. P. Abbracchio, G. Burnstock, J. Boeynaems et al. , "International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy, " Pharmacological Reviews, vol. 58, no. 3, pp. 281-341, 2006.
79. R. L. Carter, I. P. Fricks, M. O. Barrett et al. , "Quantification of Gi-mediated inhibition of adenylyl cyclase activity reveals that UDP is a potent agonist of the human P2Y14 receptor, " Molecular Pharmacology, vol. 76, no. 6, pp. 1341-1348, 2009.
80. Z. Gerevich, C. Müller, and P. Illes, "Metabotropic P2Y1 receptors inhibit P2X3 receptor-channels in rat dorsal root ganglion neurons, " European Journal of Pharmacology, vol. 521, no. 1-3, pp. 34-38, 2005.
81. S. A. Malin andD. C. Molliver, "Gi-andGq-coupledADP (P2Y) receptors act in opposition to modulate nociceptive signaling and inflammatory pain behavior, "Molecular Pain, vol. 6, article 21, 2010.
82. M. Tominaga, M. Wada, and M. Masu, "Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia, " Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 12, pp. 6951-6956, 2001.
83. T. Moriyama, T. Iida, K. Kobayashi et al. , "Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity, " Journal of Neuroscience, vol. 23, no. 14, pp. 6058-6062, 2003.
84. S. Koizumi, Y. Shigemoto-Mogami, K. Nasu-Tada et al. , "UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis, " Nature, vol. 446, no. 7139, pp. 1091-1095, 2007.
85. K. Kobayashi, H. Yamanaka, T. Fukuoka, Y. Dai, K. Obata, and K. Noguchi, "P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain, " Journal of Neuroscience, vol. 28, no. 11, pp. 2892-2902, 2008.
86. H. Tozaki-Saitoh, M. Tsuda, H. Miyata, K. Ueda, S. Kohsaka, and K. Inoue, "P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury, " Journal of Neuroscience, vol. 28, no. 19, pp. 4949-4956, 2008.
87. K. Kobayashi, H. Yamanaka, F. Yanamoto, M. Okubo, and K. Noguchi, "Multiple P2Y subtypes in spinal microglia are involved in neuropathic pain after peripheral nerve injury, " Glia, vol. 60, no. 10, pp. 1529-1539, 2012.
88. L. P. Bernier, A. R. Ase, É. Boué-Grabot, and P. Séguéla, "Inhibition of P2X4 function by P2Y6 UDP receptors in microglia, " Glia, vol. 61, no. 12, pp. 2038-2049, 2013.
89. F. Di Virgilio, S. Ceruti, P. Bramanti, and M. P. Abbracchio, "Purinergic signalling in inflammation of the central nervous system, " Trends in Neurosciences, vol. 32, no. 2, pp. 79-87, 2009.
90. M. Xia and Y. Zhu, "Signaling pathways of ATP-induced PGE2 release in spinal cord astrocytes are EGFR transactivationdependent, " GLIA, vol. 59, no. 4, pp. 664-674, 2011.
91. M. Boccazzi, C. Rolando, M. P. Abbracchio et al. , "Purines regulate adult brain subventricular zone cell functions: contribution of reactive astrocytes, " Glia, vol. 62, pp. 428-439, 2014.
92. K. Kobayashi, H. Yamanaka, and K. Noguchi, "Expression of ATP receptors in the rat dorsal root ganglion and spinal cord, " Anatomical Science International, vol. 88, no. 1, pp. 10-16, 2013.
93. G. Villa, M. Fumagalli, C. Verderio, M. P. Abbracchio, and S. Ceruti, "Expression and contribution of satellite glial cells purinoceptors to pain transmission in sensory ganglia: an update, " Neuron Glia Biology, vol. 6, no. 1, pp. 31-42, 2010.
94. K. Kobayashi, T. Fukuoka, H. Iyamanaka et al. , "Neurons and glial cells differentially express P2Y receptor mRNAs in the rat dorsal root ganglion and spinal cord, " Journal of Comparative Neurology, vol. 498, no. 4, pp. 443-454, 2006.
95. S. Ceruti, G. Villa, M. Fumagalli et al. , "Calcitonin gene-related peptide-mediated enhancement of purinergic neuron/glia communication by the algogenic factor bradykinin in mouse trigeminal ganglia from wild-type and R192Q Cav2. 1 knockin mice: Implications for basic mechanisms of migraine pain, " Journal of Neuroscience, vol. 31, no. 10, pp. 3638-3649, 2011.
96. N. Li, Z. Y. Lu, L. H. Yu et al. , "Inhibition of G protein-coupled P2Y2 receptor induced analgesia in a rat model of trigeminal neuropathic pain, " Molecular Pain, vol. 10, article 21, 2014.
97. A. Katagiri, M. Shinoda, K. Honda, A. Toyofuku, B. J. Sessle, andK. Iwata, "Satellite glial cellP2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats, " Molecular Pain, vol. 8, article 23, 2012.
98. J. F. Chen, H. K. Eltzschig, and B. B. Fredholm, "Adenosine receptors as drug targets-what are the challenges?" Nature Reviews Drug Discovery, vol. 12, no. 4, pp. 265-286, 2013.
99. J. Sawynok, A. R. Reid, and J. Liu, "Spinal and peripheral adenosine A1 receptors contribute to antinociception by tramadol in the formalin test in mice, " European Journal of Pharmacology, vol. 714, no. 1-3, pp. 373-378, 2013.
100. J. Liu, A. R. Reid, and J. Sawynok, "Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, " Neuroscience Letters, vol. 536, no. 1, pp. 64-68, 2013.
101. J. Liu, A. R. Reid, and J. Sawynok, "Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, are involved in antinociception by systemically administered amitriptyline, " European Journal of Pharmacology, vol. 698, no. 1-3, pp. 213-219, 2013.
102. X. Gao, Q. Lu, G. Chou et al. , "Norisoboldine attenuates inflammatory pain via the adenosine A1 receptor, " European Journal of Pain, vol. 18, no. 7, pp. 939-948, 2014.
103. L. Luongo, R. Petrelli, L. Gatta et al. , "5'-Chloro-5'-deoxy-(±)-ENBA, a potent and selective adenosine A1 receptor agonist, alleviates neuropathic pain in mice through functional glial and microglial changes without affecting motor or cardiovascular functions, " Molecules, vol. 17, no. 12, pp. 13712-13726, 2012.
104. L. Luongo, F. Guida, R. Imperatore et al. , "The A1 adenosine receptor as a new player in microglia physiology, " Glia, vol. 62, no. 1, pp. 122-132, 2014.
105. S. Ferré, I. Diamond, S. R. Goldberg et al. , "Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry: implications for drug addiction, sleep and pain, " Progress in Neurobiology, vol. 83, no. 5, pp. 332-347, 2007.
106. L. Li, J. X. Hao, B. B. Fredholm, G. Schulte, Z. Wiesenfeld-Hallin, and X. J. Xu, "Peripheral adenosine A2A receptors are involved in carrageenan-induced mechanical hyperalgesia in mice, " Neuroscience, vol. 170, no. 3, pp. 923-928, 2010.
107. J. M. Pocock and H. Kettenmann, "Neurotransmitter receptors on microglia, " Trends in Neurosciences, vol. 30, no. 10, pp. 527-535, 2007.
108. L. C. Loram, F. R. Taylor, K. A. Strand et al. , "Intrathecal injection of adenosine 2A receptor agonists reversed neuropathic allodynia through protein kinase (PK)A/PKC signaling, " Brain, Behavior, and Immunity, vol. 33, pp. 112-122, 2013.
109. Z. Chen, K. Janes, C. Chen et al. , "Controlling murine and rat chronic pain through A3 adenosine receptor activation, " The FASEB Journal, vol. 26, no. 5, pp. 1855-1865, 2012.
110. K. Ohsawa, T. Sanagi, Y. Nakamura, E. Suzuki, K. Inoue, and S. Kohsaka, "Adenosine A3 receptor is involved in ADPinduced microglial process extension and migration, " Journal of Neurochemistry, vol. 121, no. 2, pp. 217-227, 2012.
111. E. Daré, G. Schulte, O. Karovic, C. Hammarberg, and B. B. Fredholm, "Modulation of glial cell functions by adenosine receptors, " Physiology and Behavior, vol. 92, no. 1-2, pp. 15-20, 2007.
112. L. Antonioli, B. Csóka, M. Fornai et al. , "Adenosine and inflammation: what's new on the horizon?" Drug Discovery Today, vol. 19, no. 8, pp. 1051-1068, 2014.
113. A. P. Ford, "P2X3 antagonists: novel therapeutics for afferent sensitization and chronic pain, " Pain Management, vol. 2, pp. 267-277, 2012.
114. M. Furber, L. Alcaraz, J. E. Bent et al. , "Discovery of potent and selective adamantane-based small-molecule P2X7 receptor antagonists/interleukin-1β inhibitors, " Journal of Medicinal Chemistry, vol. 50, no. 24, pp. 5882-5885, 2007.
115. V. Hernandez-Olmos, A. Abdelrahman, A. El-Tayeb, D. Freudendahl, S. Weinhausen, and C. E. Müller, "N-substituted phenoxazine and acridone derivatives: structure-activity relationships of potent P2X4 receptor antagonists, " Journal of Medicinal Chemistry, vol. 55, no. 22, pp. 9576-9588, 2012.
116. K. Zhang, J. Zhang, Z. G. Gao et al. , "Structure of the human P2Y12 receptor in complex with an antithrombotic drug, " Nature, vol. 509, pp. 115-118, 2014.
117. F. Vincenzi, M. Targa, R. Romagnoli et al. , "TRR469, a potent A1 adenosine receptor allosteric modulator, exhibits antinociceptive properties in acute and neuropathic pain models in mice, " Neuropharmacology, vol. 81, pp. 6-14, 2014.
118. S. Koizumi, K. Ohsawa, K. Inoue, and S. Kohsaka, "Purinergic receptors in microglia: functional modal shifts of microglia mediated by P2 and P1 receptors, " Glia, vol. 61, no. 1, pp. 47-54, 2013.