P2 receptors and chronic pain

Purinergic Signalling

Volumn 3, Issue 1-2, 2007, Pages 135-144

  Inoue, Kazuhide ^a  

^a KYUSHU UNIVERSITY   (Japan)

Author keywords

Allodynia; ATP; Microglia; Neuropathic pain; P2X4; p38; Spinal cord

Indexed keywords

EID: 33947629663     PISSN: 15739538     EISSN: 15739546     Source Type: Journal    
DOI: 10.1007/s11302-006-9045-8     Document Type: Review

References (133)

1. Bleehen T, Hobbiger F, Keele CA (1976) Identification of algogenic substances in human erythrocytes. J Physiol 262:131-149
2. Bleehen T, Keele CA (1977) Observations on the algogenic actions of adenosine compounds on the human blister base preparation. Pain 3:367-377
3. Chen CC, Akopian AN, Sivilotti L et al (1995) A P2X purinoceptor expressed by a subset of sensory neurons. Nature 377:428-431
4. Lewis C, Neidhart S, Holy C et al (1995) Coexpression of P2X2 and P2X3 receptor subunits can account for ATP- gated currents in sensory neurons. Nature 377:432-435
5. Burnstock G, Wood JN (1996) Purinergic receptors: Their role in nociception and primary afferent neurotransmission. Curr Opin Neurobiol 6:526-532
6. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413-492
7. Burnstock G (2000) P2X receptors in sensory neurones. Br J Anaesth 84:476-488
8. 2+ by speeding recovery of P2X receptors from desensitization. J Neurosci 18:9238-9244
9. Ueno S, Tsuda M, Iwanaga T et al (1999) Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons. Br J Pharmacol 126:429-436
10. Li C, Peoples RW, Lanthorn TH et al (1999) Distinct ATP-activated currents in different types of neurons dissociated from rat dorsal root ganglion. Neurosci Lett 263:57-60
11. Tsuda M, Koizumi S, Kita A et al (2000) 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. J Neurosci 20:RC90
12. Chizh BA, Illes P (2001) P2X receptors and nociception. Pharmacol Rev 53:553-568
13. Dunn PM, Zhong Y, Burnstock G (2001) P2X receptors in peripheral neurons. Prog Neurobiol 65:107-134
14. 2+ stores exclusively in large DRG neurones. Neuroreport 8:1555-1559
15. Koizumi S, Tsuda M, Shigemoto Y et al (2001) Characterization of P2Y receptors in cultured rat dorsal root ganglion neurons. Jpn J Pharmacol 85:149P
16. Sanada M, Yasuda H, Omatsu-Kanbe M et al (2002) Increase in intracellular Ca(2+) and calcitonin gene-related peptide release through metabotropic P2Y receptors in rat dorsal root ganglion neurons. Neuroscience 111:413-422
17. Tominaga M, Wada M, Masu M (2001) Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc Natl Acad Sci USA 98:6951-6956
18. Molliver DC, Cook SP, Carlsten JA et al (2002) ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2. Eur J Neurosci 16:1850-1860
19. Moriyama T, Iida T, Kobayashi K et al (2003) Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity. J Neurosci 23:6058-6062
20. Cockayne DA, Hamilton SG, Zhu QM et al (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407:1011-1015
21. Souslova V, Cesare P, Ding Y et al (2000) Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407:1015-1017
22. 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
23. Hamilton SG, Wade A, McMahon SB (1999) The effects of inflammation and inflammatory mediators on nociceptive behaviour induced by ATP analogues in the rat. Br J Pharmacol 126:326-332
24. Bland-Ward PA, Humphrey PP (1997) Acute nociception mediated by hindpaw P2X receptor activation in the rat. Br J Pharmacol 122:365-371
25. Tsuda M, Ueno S, Inoue K (1999) In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: Involvement of the glutamate-NMDA receptor system. Br J Pharmacol 127:449-456
26. Dorn G, Abdel'Al S, Natt FJ et al (2001) Specific inhibition of the rat ligand-gated ion channel P2X3 function via methoxyethoxy-modified phosphorothioated antisense oligonucleotides. Antisense Nucleic Acid Drug Dev 11:165-174
27. Barclay J, Patel S, Dorn G et al (2002) Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain. J Neurosci 22:8139-8147
28. Tsuda M, Shigemoto-Mogami Y, Ueno S et al (2002) Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain. Eur J Neurosci 15:1444-1450
29. Dai Y, Fukuoka T, Wang H et al (2004) Contribution of sensitized P2X receptors in inflamed tissue to the mechanical hypersensitivity revealed by phosphorylated ERK in DRG neurons. Pain 108:258-266
30. Woolf CJ, Mannion RJ (1999) Neuropathic pain: Aetiology, symptoms, mechanisms, and management. Lancet 353:1959-1964
31. Woolf CJ, Salter MW (2000) Neuronal plasticity: Increasing the gain in pain. Science 288:1765-1769
32. Scholz J, Woolf CJ (2002) Can we conquer pain? Nat Neurosci 5:1062-1067
33. Tsuzuki K, Kondo E, Fukuoka T et al (2001) Differential regulation of P2X(3) mRNA expression by peripheral nerve injury in intact and injured neurons in the rat sensory ganglia. Pain 91:351-360
34. Kennedy C, Assis TS, Currie AJ et al (2003) Crossing the pain barrier: P2 receptors as targets for novel analgesics. J Physiol 553:683-694
35. Casula MA, Chessell IP, Bountra C, Yiangou Y, Birch R, Anand P (2004) Increase of purinergic receptor P2X7 in injured human nerves anddorsal root ganglia. J Neurol Neurosurg Psychiatry 75:1227-1231
36. Chessell P, Hatcher JP, Bountra C, Michel AD, Hughes JP, Green P et al (2005) Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 114:386-396
37. 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
38. Coull JAM, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438:1017-1021
39. Kreutzberg GW (1996) Microglia: A sensor for pathological events in the CNS. Trends Neurosci 19:312-318
40. Stoll G, Jander S (1999) The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58:233-247
41. Perry VH (1994) Modulation of microglia phenotype. Neuropathol Appl Neurobiol 20:177-184
42. Wall PD, Devor M, Inbal R et al (1979) Autotomy following peripheral nerve lesions: Experimental anaesthesia dolorosa. Pain 7:103-111
43. Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87-107
44. Seltzer Z, Dubner R, Shir Y (1990) A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43:205-218
45. Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:355-363
46. Decosterd I, Woolf CJ (2000) Spared nerve injury: An animal model of persistent peripheral neuropathic pain. Pain 87:149-158
47. Eriksson NP, Persson JK, Svensson M et al (1993) A quantitative analysis of the microglial cell reaction in central primary sensory projection territories following peripheral nerve injury in the adult rat. Exp Brain Res 96:19-27
48. Colburn RW, DeLeo JA, Rickman AJ et al (1997) Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat. J Neuroimmunol 79:163-175
49. 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
50. Colburn RW, Rickman AJ, DeLeo JA (1999) The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp Neurol 157:289-304
51. Stuesse SL, Cruce WL, Lovell JA et al (2000) Microglial proliferation in the spinal cord of aged rats with a sciatic nerve injury. Neurosci Lett 287:121-124
52. Gehrmann J, Banati RB (1995) Microglial turnover in the injured CNS: activated microglia undergo delayed DNA fragmentation following peripheral nerve injury. J Neuropathol Exp Neurol 54:680-688
53. Liu L, Tornqvist E, Mattsson P et al (1995) Complement and clusterin in the spinal cord dorsal horn and gracile nucleus following sciatic nerve injury in the adult rat. Neuroscience 68:167-179
54. Watkins LR, Milligan ED, Maier SF (2001) Glial activation: A driving force for pathological pain. Trends Neurosci 24:450-455
55. Surprenant A, Rassendren F, Kawashima E et al (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272:735-738
56. Khakh BS, Burnstock G, Kennedy C et al (2001) International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev 53:107-118
57. Virginio C, Robertson G, Surprenant A et al (1998) Trinitrophenyl-substituted nucleotides are potent antagonists selective for P2X1, P2X3, and heteromeric P2X2/3 receptors. Mol Pharmacol 53:969-973
58. Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, De Koninck P, De Koninck Y (2003) Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424:938-942
59. Mannion RJ et al (1999) Neurotrophins: Peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. Proc Natl Acad Sci USA 96:9385-9390
60. Heppenstall PA, Lewin GR (2001) BDNF but not NT-4 is required for normal flexion reflex plasticity and function. Proc Natl Acad Sci USA 98:8107-8112
61. Thompson SW, Bennett DL, Kerr BJ et al (1999) Brain-derived neurotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord. Proc Natl Acad Sci USA 96:7714-7718
62. - cotransporter KCC2 and impairs neuronal Cl - extrusion. J Cell Biol 159:747-752
63. Gravel C, Gotz R, Lorrain A, Sendtner M (1997) Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to longterm survival of axotomized motor neurons. Nature Med 3:765-770
64. 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
65. Winkelstein BA, Rutkowski MD, Sweitzer SM et al (2001) Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment. J Comp Neurol 439:127-139
66. Raghavendra V, Tanga F, DeLeo JA (2003) Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 306:624-630
67. Robertson B, Xu XJ, Hao JX et al (1997) Interferon-gamma receptors in nociceptive pathways: Role in neuropathic pain-related behaviour. Neuroreport 8:1311-1316
68. DeLeo JA, Yezierski RP (2001) The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90:1-6
69. Wagner R, Myers RR (1996) Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. NeuroReport 7:2897-2901
70. Sommer C, Schäfers M (1998) Painful mononeuropathy in C57BL/Wld mice with delayed Wallerian degeneration: Differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity. Brain Res 784:154-162
71. Sommer C, Marziniak M, Myers RR (1998) The effect of thalidomide treatment on vascular pathology and hyperalgesia caused by chronic constriction injury of rat nerve. Pain 74:83-91
72. Sorkin LS, Doom CM (2000) Epineurial application of TNF elicits an acute mechanical hyperalgesia in the awake rat. J Peripher Nerv Syst 5:96-100
73. Schäfers M, Geis C, Brors D, Yaksh TL, Sommer C (2002) Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve. J Neurosci 22:536-545
74. Schäfers M, Lee DH, Brors D, Yaksh TL, Sorkin LS (2003) Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation. J Neurosci 23:3028-3038
75. Hashizume H, DeLeo, JA, Colburn RW, Weinstein JN (2000) Spinal glial activation and cytokine expression after lumbar root injury in the rat. Spine 25:1206-1217
76. Sommer C, Schäfers M, Marziniak M, Toyka KV (2001) Etanercept reduces hyperalgesia in experimental painful neuropathy. J Peripher Nerv Syst 6:67-72
77. Sommer C, Lindenlaub T, Teuteberg P, Schäfers M, Hartung T, Toyka KV (2001) Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy. Brain Res 913:86-89
78. Homma Y, Brull SJ, Zhang JM (2002) A comparison of chronic pain behavior following local application of tumor necrosis factor-alpha to the normal and mechanically compressed lumbar ganglia in the rat. Pain 95:239-246
79. + conductance in an identified neuron of Aplysia kurodai. Neurosci Lett 115:219-225
80. 2+ currents in cultured sympathetic neurons. J Neurosci 12:2665-2671
81. Sorkin LS, Xiao WH, Wagner R, Myers RR (1997) Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 81:255-262
82. Furukawa K, Mattson MP (1998) The transcription factor NF-kappa B mediates increases in calcium currents and decreases in NMDA- and AMPA/ kainate-induced currents induced by tumor necrosis factor-alpha in hippocampal neurons. J Neurochem 70:1876-1886
83. Junger H, Sorkin LS (2000) Nociceptive and inflammatory effects of subcutaneous TNF-α. Pain 85:145-151
84. Diem R, Meyer R, Weishaupt JH, Bahr M (2001) Reduction of potassium currents and phosphatidylinositol 3-kinase-dependent Akt phosphorylation by tumor necrosis factor-α rescues axotomized retinal ganglion cells from retrograde cell death in vivo. J Neurosci 21:2058-2066
85. Leem JG, Bove GM (2002) Mid-axonal tumor necrosis factor-alpha induces ectopic activity in a subset of slowly conducting cutaneous and deep afferent neurons. J Pain 3:45-49
86. Hide I, Tanaka M, Inoue A et al (2000) Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia. J Neurochem 75:965-972
87. Suzuki T, Hide I, Ido K et al (2004) Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. J Neurosci 24:1-7
88. 2+ mobilisation and stress kinases in cultured sensory neurones. Neuropharmacology 42:93-106
89. Ji R, Samad T, Jin S, Schmoll R, Woolf C (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 3:57-68
90. Milligan ED, Twining C, Chacur M, Biedenkapp J, O'Connor K, Poole S (2003) Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci 23:1026-1040
91. Jin SX, Zhuang ZY, Woolf CJ et al (2003) p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci 23:4017-4022
92. 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
93. Schäfers M, Svensson CI, Sommer C, Sorkin LS (2003) Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons. J Neurosci 23:2517-2521
94. Onda A, Murata Y, Rydevik B, Larsson K, Kikuchi S, Olmarker K (2004) Infliximab attenuates immunoreactivity of brain-derived neurotrophic factor in a rat model of herniated nucleus pulposus. Spine 29:1857-1861
95. Ferrari D, Villalba M, Chiozzi P, Falzoni S, Ricciardi-Castagnoli P, Di Virgilio F (1996) Mouse microglial cells express a plasma membrane pore gated by extracellular ATP. J Immunol 156:1531-1539
96. Ferrari D, Chiozzi P, Falzoni S, Hanau S, Di Virgilio F (1997) Purinergic modulation of interleukin-1 beta release from microglial cells stimulated with bacterial endotoxin. J Exp Med 185:579-582
97. Sanz JM, Di Virgilio F (2000) Kinetics and mechanism of ATP-dependent IL-1 beta release from microglial cells. J Immunol 164:4893-4898
98. Perregaux D, Gabel CA (1994) Interleukin-1 maturation and release in response to ATP and nigericin. J Biol Chem 269:15195-15203
99. Kerr BJ, Bradbury EJ, Bennett DL et al (1999) Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord. J Neurosci 19:5138-5148
100. Vikman KS, Hill RH, Backstrom E et al (2003) Interferon-gamma induces characteristics of central sensitization in spinal dorsal horn neurons in vitro. Pain 106:241-251
101. Viviani B, Bartesaghi S, Gardoni F et al (2003) Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 23:8692-8700
102. Yu XM, Askalan R, Keil GJ 2nd et al (1997) NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275:674-678
103. Wang S, Cheng Q, Malik S et al (2000) Interleukin-1beta inhibits gamma-aminobutyric acid type A (GABA(A)) receptor current in cultured hippocampal neurons. J Pharmacol Exp Ther 292:497-504
104. Hamilton SG, Warburton J, Bhattacharjee A, Ward J, McMahon SB (2000) ATP in human skin elicits a dose-related pain response which is potentiated under conditions of hyperalgesia. Brain 123:1238-1246
105. Hamilton SG, McMahon SB, Lewin GR (2001) Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin. J Physiol 534:437-445
106. Ryan LM, Rachow JW, McCarty DJ (1991) Synovial fluid ATP: A potential substrate for the production of inorganic pyrophosphate. J Rheumatol 18:716-720
107. Park W, Masuda I, Cardenal-Escarcena A, Palmer DL, McCarty DJ (1996) Inorganic pyrophosphate generation from adenosine triphosphate by cell-free human synovial fluid. J Rheumatol 23:665-671
108. Dell'Antonio G, Quattrini A, Cin ED, Fulgenzi A, Ferrero ME (2002) Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP. Arthritis Rheum 46:3378-3385
109. Dell'Antonio G, Quattrini A, Dal Cin E, Fulgenzi A, Ferrero ME (2002) Antinociceptive effect of a new P2Z/P2X7 antagonist, oxidized ATP, in arthritic rats. Neurosci Lett 327:87-90
110. McGaraughty S, Wismer CT, Zhu CZ, Mikusa J, Honore P, Chu KL, Lee CH, Faltynek CR, Jarvis MF (2003) Effects of A-317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration. Br J Pharmacol 140:1381-1388
111. Honore P, Kage K, Mikusa J et al (2002) Analgesic profile of intrathecal P2X(3) antisense oligonucleotide treatment in chronic inflammatory and neuropathic pain states in rats. Pain 99:11-19
112. Wu G, Whiteside GT, Lee G, Nolan S, Niosi M, Pearson MS, Ilyin VI (2004) A-317491, a selective P2X3/P2X2/3 receptor antagonist, reverses inflammatory mechanical hyperalgesia through action at peripheral receptors in rats. Eur J Pharmacol 504:45-53
113. Xu GY, Huang LY (2002) Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons. J Neurosci 22:93-102
114. 2+ waves in keratinocytes are transmitted to sensory neurons: The involvement of extracellular ATP and P2Y2 receptor activation. Biochem J 380:329-338
115. Julius D, Basbaum AI (2001) Molecular mechanisms of nociception. Nature 413:203-210
116. Hu HZ, Li ZW (1996) Substance P potentiates ATP-activated currents in rat primary sensory neurons. Brain Res 739:163-168
117. Paukert M, Osteroth R, Geisler HS, Brandle U, Glowatzki E, Ruppersberg JP, Grunder S (2001) Inflammatory mediators potentiate ATP-gated channels through the P2X3 subunit. J Biol Chem 276:21077-21082
118. Wang MJ, Xiong SH, Li ZW (2001) Neurokinin B potentiates ATP-activated currents in rat DRG neurons. Brain Res 923:157-162
119. Li C, Peoples RW, Weight FF (1997) Enhancement of ATP-activated current by protons in dorsal root ganglion neurons. Pflugers Arch 433:446-454
120. Ramer MS, Bradbury EJ, McMahon SB (2001) Nerve growth factor induces P2X3 expression in sensory neurons. J Neurochem 77:864-875
121. Bradbury EJ, Burnstock G, McMahon SB (1998) The expression of P2X3 purinoreceptors in sensory neurons: Effects of axotomy and glial-derived neurotrophic factor. Mol Cell Neurosci 12:256-268
122. Novakovic SD, Kassotakis LC, Oglesby IB, Smith JA, Eglen RM, Ford AP, Hunter JC (1999) Immunocytochemical localization of P2X3 purinoceptors in sensory neurons in naive rats and following neuropathic injury. Pain 80:273-282
123. Eriksson J, Bongenhielm U, Kidd E, Matthews B, Fried K (1998) Distribution of P2X3 receptors in the rat trigeminal ganglion after inferior alveolar nerve injury. Neurosci Lett 254:37-40
124. Kim C, Chung JM, Chung K (2003) Changes in the gene expression of six subtypes of P2X receptors in rat dorsal root ganglion after spinal nerve ligation. Neurosci Lett 337:81-84
125. Dorn G, Patel S, Wotherspoon G, Hemmings-Mieszczak M, Barclay J, Natt FJ, Martin P, Bevan S, Fox A, Ganju P, Wishart W, Hall J (2004) siRNA relieves chronic neuropathic pain. Nucleic Acids Res 32:e49
126. Kage K, Niforatos W, Zhu CZ, Lynch KJ, Honore P, Jarvis MF (2002) Alteration of dorsal root ganglion P2X3 receptor expression and function following spinal nerve ligation in the rat. Exp Brain Res 147:511-519
127. Cook SP, McCleskey EW (2002) Cell damage excites nociceptors through release of cytosolic ATP. Pain 95:41-47
128. 2+ waves in keratinocytes are transmitted to sensory neurons: The involvement of extracellular ATP and P2Y2 receptor activation. Biochem J 380:329-338
129. Vulchanova L, Riedl MS, Shuster SJ, Stone LS, Hargreaves KM, Buell G, Surprenant A, North RA, Elde R (1998) P2X3 is expressed by DRG neurons that terminate in inner lamina II. Eur J Neurosci 10:3470-3478
130. Nakatsuka T, Gu JG (2001) ATP P2X receptor-mediated enhancement of glutamate release and evoked EPSCs in dorsal horn neurons of the rat spinal cord. J Neurosci 21:6522-6531
131. Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241-245
132. 2+ wave propagation in dorsal spinal cord astrocytes. J Neurosci 20:2800-2808
133. Watkins LR, Maier SF (2003) GLIA: A novel drug discovery target for clinical pain. Nat Rev Drug Discov 2:973-985