Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury

GLIA

Volumn 60, Issue 11, 2012, Pages 1660-1670

  Chen, Michael J ^a   Kress, Benjamin ^a   Han, Xiaoning ^a   Moll, Katherine ^a   Peng, Weiguo ^a   Ji, Ru Rong ^b   Nedergaard, Maiken ^a  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Astrocyte; ATP; Chronic pain; Connexin 43; P2X; Spinal cord injury

Indexed keywords

CONNEXIN 30; CONNEXIN 43; GLIAL FIBRILLARY ACIDIC PROTEIN; MINOCYCLINE;

ALLODYNIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; CHRONIC PAIN; CONTROLLED STUDY; FEMALE; GAP JUNCTION; GLIOSIS; HYPERALGESIA; INFLAMMATION; LOCOMOTION; MOUSE; NEUROPATHIC PAIN; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SPINAL CORD INJURY; UPREGULATION;

ANIMALS; ASTROCYTES; CONNEXIN 43; DISEASE MODELS, ANIMAL; FEMALE; GAP JUNCTIONS; GLIAL FIBRILLARY ACIDIC PROTEIN; HYPERALGESIA; MICE; MICE, KNOCKOUT; NEURALGIA; PAIN MEASUREMENT; PAIN THRESHOLD; SPINAL CORD; SPINAL CORD INJURIES;

EID: 84865864997     PISSN: 08941491     EISSN: 10981136     Source Type: Journal    
DOI: 10.1002/glia.22384     Document Type: Article

References (93)

1. Basso DM, Fisher LC, Anderson AJ, Jakeman LB, McTigue DM, Popovich PG. 2006. Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. J Neurotrauma 23: 635-659.
2. Beare JE, Morehouse JR, DeVries WH, Enzmann GU, Burke DA, Magnuson DS, Whittemore SR. 2009. Gait analysis in normal and spinal contused mice using the TreadScan system. J Neurotrauma 26: 2045-2056.
3. Bennett MV, Contreras JE, Bukauskas FF, Saez JC. 2003. New roles for astrocytes: Gap junction hemichannels have something to communicate. Trends Neurosci 26: 610-617.
4. Bethea JR. 2000. Spinal cord injury-induced inflammation: A dual-edged sword. Prog Brain Res 128: 33-42.
5. Brederson JD, Jarvis MF. 2008. Homomeric and heteromeric P2X3 receptors in peripheral sensory neurons. Curr Opin Investig Drugs 9: 716-725.
6. Chen M, Gu JG. 2005. A P2X receptor-mediated nociceptive afferent pathway to lamina I of the spinal cord. Mol Pain 1: 4.
7. Chen T, Koga K, Li XY, Zhuo M. 2010. Spinal microglial motility is independent of neuronal activity and plasticity in adult mice. Mol Pain 6: 19.
8. Chessell IP, Hatcher JP, Bountra C, Michel AD, Hughes JP, Green P, Egerton J, Murfin M, Richardson J, Peck WL, et al. 2005. Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 114: 386-396.
9. Clark AK, Staniland AA, Marchand F, Kaan TK, McMahon SB, Malcangio M. 2010. P2X7-dependent release of interleukin-1β and nociception in the spinal cord following lipopolysaccharide. J Neurosci 30: 573-582.
10. Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA, Buell G. 1997. Tissue distribution of the P2X7 receptor. Neuropharmacology 36: 1277-1283.
11. Contreras JE, Sanchez HA, Eugenin EA, Speidel D, Theis M, Willecke K, Bukauskas FF, Bennett MV, Saez JC. 2002. Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Proc Natl Acad Sci USA 99: 495-500.
12. Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M. 1998. Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 95: 15735-15740.
13. Cotrina ML, Nedergaard M. 2009. Physiological and pathological functions of P2X7 receptor in the spinal cord. Purinergic Signal 5: 223-232.
14. Cronin M, Anderson PN, Cook JE, Green CR, Becker DL. 2008. Blocking connexin43 expression reduces inflammation and improves functional recovery after spinal cord injury. Mol Cell Neurosci 39: 152-160.
15. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. 2005. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8: 752-758.
16. DeLeo JA, Yezierski RP. 2001. The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90: 1-6.
17. Dell'Antonio G, Quattrini A, Cin ED, Fulgenzi A, Ferrero ME. 2002a. Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP. Arthritis Rheum 46: 3378-3385.
18. Dell'Antonio G, Quattrini A, Dal Cin E, Fulgenzi A, Ferrero ME. 2002b. Antinociceptive effect of a new P(2Z)/P2X7 antagonist, oxidized ATP, in arthritic rats. Neurosci Lett 327: 87-90.
19. Di Virgilio F, Ceruti S, Bramanti P, Abbracchio MP. 2009. Purinergic signalling in inflammation of the central nervous system. Trends Neurosci 32: 79-87.
20. Di Virgilio F, Sanz JM, Chiozzi P, Falzoni S. 1999. The P2Z/P2X7 receptor of microglial cells: A novel immunomodulatory receptor. Prog Brain Res 120: 355-368.
21. Donnelly-Roberts DL, Jarvis MF. 2007. Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Br J Pharmacol 151: 571-579.
22. Duan S, Anderson CM, Keung EC, Chen Y, Swanson RA. 2003. P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci 23: 1320-1328.
23. Evans WH, De Vuyst E, Leybaert L. 2006. The gap junction cellular internet: Connexin hemichannels enter the signalling limelight. Biochem J 397: 1-14.
24. Farahani R, Pina-Benabou MH, Kyrozis A, Siddiq A, Barradas PC, Chiu FC, Cavalcante LA, Lai JC, Stanton PK, Rozental R. 2005. Alterations in metabolism and gap junction expression may determine the role of astrocytes as "good samaritans" or executioners. Glia 50: 351-361.
25. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. 2004. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24: 2143-2155.
26. Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A, Idzko M, Panther E, Di Virgilio F. 2006. The P2X7 receptor: A key player in IL-1 processing and release. J Immunol 176: 3877-3883.
27. Franke H, Grummich B, Hartig W, Grosche J, Regenthal R, Edwards RH, Illes P, Krugel U. 2006. Changes in purinergic signaling after cerebral injury-Involvement of glutamatergic mechanisms? Int J Dev Neurosci 24: 123-132.
28. Friedle SA, Curet MA, Watters JJ. 2010. Recent patents on novel P2X(7) receptor antagonists and their potential for reducing central nervous system inflammation. Recent Pat CNS Drug Discov 5: 35-45.
29. Gallagher CJ, Salter MW. 2003. Differential properties of astrocyte calcium waves mediated by P2Y1 and P2Y2 receptors. J Neurosci 23: 6728-6739.
30. Gao YJ, Ji RR. 2010. Targeting astrocyte signaling for chronic pain. Neurotherapeutics 7: 482-493.
31. Garre JM, Retamal MA, Cassina P, Barbeito L, Bukauskas FF, Saez JC, Bennett MV, Abudara V. 2010. FGF-1 induces ATP release from spinal astrocytes in culture and opens pannexin and connexin hemichannels. Proc Natl Acad Sci USA 107: 22659-22664.
32. Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W, Jensen TK, Pei Y, Wang F, Han X, et al. 2010. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci 13: 883-888.
33. Gourine AV, Poputnikov DM, Zhernosek N, Melenchuk EV, Gerstberger R, Spyer KM, Gourine VN. 2005. P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats. Br J Pharmacol 146: 139-145.
34. Gwak YS, Hulsebosch CE. 2011. Neuronal hyperexcitability: A substrate for central neuropathic pain after spinal cord injury. Curr Pain Headache Rep 15: 215-222.
35. Hains BC, Waxman SG. 2006. Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J Neurosci 26: 4308-4317.
36. Hua XY, Svensson CI, Matsui T, Fitzsimmons B, Yaksh TL, Webb M. 2005. Intrathecal minocycline attenuates peripheral inflammation-induced hyperalgesia by inhibiting p38 MAPK in spinal microglia. Eur J Neurosci 22: 2431-2440.
37. Huang C, Han X, Li X, Lam E, Peng W, Lou N, Torres A, Yang M, Mauricio Garre J, Tian G, et al. 2012. Critical role of connexin 43 in secondary expansion of traumatic spinal cord injury. J Neurosci 32: 3333-3338.
38. Hughes JP, Hatcher JP, Chessell IP. 2007. The role of P2X in pain and inflammation. Purinergic Signal 3: 163-169.
39. Hulsebosch CE, Hains BC, Crown ED, Carlton SM. 2009. Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain Res Rev 60: 202-213.
40. Iglesias R, Dahl G, Qiu F, Spray DC, Scemes E. 2009. Pannexin 1: The molecular substrate of astrocyte "hemichannels." J Neurosci 29: 7092-7097.
41. John SA, Kondo R, Wang SY, Goldhaber JI, Weiss JN. 1999. Connexin-43 hemichannels opened by metabolic inhibition. J Biol Chem 274: 236-240.
42. Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M. 2008. Connexin 43 hemichannels are permeable to ATP. J Neurosci 28: 4702-4711.
43. Kawasaki Y, Zhang L, Cheng JK, Ji RR. 2008. Cytokine mechanisms of central sensitization: Distinct and overlapping role of interleukin-1β, interleukin-6, and tumor necrosis factor-α in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 28: 5189-5194.
44. Kennedy C. 2005. P2X receptors: Targets for novel analgesics? Neuroscientist 11: 345-356.
45. Kobayashi K, Yamanaka H, Fukuoka T, Dai Y, Obata K, Noguchi K. 2008. P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain. J Neurosci 28: 2892-2902.
46. Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, Inoue K. 2007. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446: 1091-1095.
47. Labasi JM, Petrushova N, Donovan C, McCurdy S, Lira P, Payette MM, Brissette W, Wicks JR, Audoly L, Gabel CA. 2002. Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response. J Immunol 168: 6436-6445.
48. Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, Watkins LR. 2005. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 115: 71-83.
49. Lee SM, Yune TY, Kim SJ, Park DW, Lee YK, Kim YC, Oh YJ, Markelonis GJ, Oh TH. 2003. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma 20: 1017-1027.
50. Marchand F, Perretti M, McMahon SB. 2005. Role of the immune system in chronic pain. Nat Rev Neurosci 6: 521-532.
51. Matasi JJ, Brumfield S, Tulshian D, Czarnecki M, Greenlee W, Garlisi CG, Qiu H, Devito K, Chen SC, Sun Y, et al. 2011. Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: Part 1. Bioorg Med Chem Lett 21: 3805-3808.
52. Matsuka Y, Ono T, Iwase H, Mitrirattanakul S, Omoto KS, Cho T, Lam YY, Snyder B, Spigelman I. 2008. Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats. Mol Pain 4: 66.
53. Meme W, Calvo CF, Froger N, Ezan P, Amigou E, Koulakoff A, Giaume C. 2006. Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: Potentiation by β-amyloid. FASEB J 20: 494-496.
54. Milligan ED, Watkins LR. 2009. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10: 23-36.
55. Minami M, Katayama T, Satoh M. 2006. Brain cytokines and chemokines: Roles in ischemic injury and pain. J Pharmacol Sci 100: 461-470.
56. Nagy JI, Patel D, Ochalski PA, Stelmack GL. 1999. Connexin30 in rodent, cat and human brain: Selective expression in gray matter astrocytes, co-localization with connexin43 at gap junctions and late developmental appearance. Neuroscience 88: 447-468.
57. Neary JT, Kang Y, Willoughby KA, Ellis EF. 2003. Activation of extracellular signal-regulated kinase by stretch-induced injury in astrocytes involves extracellular ATP and P2 purinergic receptors. J Neurosci 23: 2348-2356.
58. Newman EA. 2005. Calcium increases in retinal glial cells evoked by light-induced neuronal activity. J Neurosci 25: 5502-5510.
59. Nie H, Zhang H, Weng HR. 2010. Minocycline prevents impaired glial glutamate uptake in the spinal sensory synapses of neuropathic rats. Neuroscience 170: 901-912.
60. Norenberg MD, Smith J, Marcillo A. 2004. The pathology of human spinal cord injury: Defining the problems. J Neurotrauma 21: 429-440.
61. O'Carroll SJ, Alkadhi M, Nicholson LF, Green CR. 2008. Connexin 43 mimetic peptides reduce swelling, astrogliosis, and neuronal cell death after spinal cord injury. Cell Commun Adhes 15: 27-42.
62. Parpura V, Scemes E, Spray DC. 2004. Mechanisms of glutamate release from astrocytes: Gap junction "hemichannels, " purinergic receptors and exocytotic release. Neurochem Int 45: 259-264.
63. Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, Takano T, Tian GF, Goldman SA, Nedergaard M. 2009. Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury. Proc Natl Acad Sci USA 106: 12489-12493.
64. 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.
65. Retamal MA, Froger N, Palacios-Prado N, Ezan P, Saez PJ, Saez JC, Giaume C. 2007. Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia. J Neurosci 27: 13781-13792.
66. Roh DH, Yoon SY, Seo HS, Kang SY, Han HJ, Beitz AJ, Lee JH. 2010. Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol 224: 123-132.
67. Rohr S. 2004. Role of gap junctions in the propagation of the cardiac action potential. Cardiovasc Res 62: 309-322.
68. Rosenzweig ES, Courtine G, Jindrich DL, Brock JH, Ferguson AR, Strand SC, Nout YS, Roy RR, Miller DM, Beattie MS, et al. 2010. Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nat Neurosci 13: 1505-1510.
69. Scemes E, Giaume C. 2006. Astrocyte calcium waves: What they are and what they do. Glia 54: 716-725.
70. Siddall PJ, McClelland JM, Rutkowski SB, Cousins MJ. 2003. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain 103: 249-257.
71. Solle M, Labasi J, Perregaux DG, Stam E, Petrushova N, Koller BH, Griffiths RJ, Gabel CA. 2001. Altered cytokine production in mice lacking P2X(7) receptors. J Biol Chem 276: 125-132.
72. Sorge RE, Trang T, Dorfman R, Smith SB, Beggs S, Ritchie J, Austin JS, Zaykin DV, Meulen HV, Costigan M, et al. 2012. Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat Med 18: 595-599.
73. Spataro LE, Sloane EM, Milligan ED, Wieseler-Frank J, Schoeniger D, Jekich BM, Barrientos RM, Maier SF, Watkins LR. 2004. Spinal gap junctions: Potential involvement in pain facilitation. J Pain 5: 392-405.
74. Springer JE, Azbill RD, Knapp PE. 1999. Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nat Med 5: 943-946.
75. Stout CE, Costantin JL, Naus CC, Charles AC. 2002. Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem 277: 10482-10488.
76. 2+ signals generated by P2Y receptor activation. Glia 48: 217-229.
77. Tan AM, Zhao P, Waxman SG, Hains BC. 2009. Early microglial inhibition preemptively mitigates chronic pain development after experimental spinal cord injury. J Rehabil Res Dev 46: 123-133.
78. Tang XQ, Heron P, Mashburn C, Smith GM. 2007. Targeting sensory axon regeneration in adult spinal cord. J Neurosci 27: 6068-6078.
79. Teubner B, Michel V, Pesch J, Lautermann J, Cohen-Salmon M, Sohl G, Jahnke K, Winterhager E, Herberhold C, Hardelin JP, et al. 2003. Connexin30 (Gjb6)-deficiency causes severe hearing impairment and lack of endocochlear potential. Hum Mol Genet 12: 13-21.
80. Theis M, de Wit C, Schlaeger TM, Eckardt D, Kruger O, Doring B, Risau W, Deutsch U, Pohl U, Willecke K. 2001. Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene. Genesis 29: 1-13.
81. Theis M, Jauch R, Zhuo L, Speidel D, Wallraff A, Doring B, Frisch C, Sohl G, Teubner B, Euwens C, et al. 2003. Accelerated hippocampal spreading depression and enhanced locomotory activity in mice with astrocyte-directed inactivation of connexin43. J Neurosci 23: 766-776.
82. Theriault E, Frankenstein UN, Hertzberg EL, Nagy JI. 1997. Connexin43 and astrocytic gap junctions in the rat spinal cord after acute compression injury. J Comp Neurol 382: 199-214.
83. Thompson RJ, Zhou N, MacVicar BA. 2006. Ischemia opens neuronal gap junction hemichannels. Science 312: 924-927.
84. Tozaki-Saitoh H, Tsuda M, Miyata H, Ueda K, Kohsaka S, Inoue K. 2008. P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. J Neurosci 28: 4949-4956.
85. Tsuda M, Inoue K, Salter MW. 2005. Neuropathic pain and spinal microglia: A big problem from molecules in "small" glia. Trends Neurosci 28: 101-107.
86. Tsuda M, Kuboyama K, Inoue T, Nagata K, Tozaki-Saitoh H, Inoue K. 2009. Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays. Mol Pain 5: 28.
87. Tsuda M, Shigemoto-Mogami Y, Koizumi S, Mizokoshi A, Kohsaka S, Salter MW, Inoue K. 2003. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424: 778-783.
88. Turner JA, Cardenas DD. 1999. Chronic pain problems in individuals with spinal cord injuries. Semin Clin Neuropsychiatry 4: 186-194.
89. Wallraff A, Kohling R, Heinemann U, Theis M, Willecke K, Steinhauser C. 2006. The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J Neurosci 26: 5438-5447.
90. Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA, et al. 2004. P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med 10: 821-827.
91. Watkins LR, Milligan ED, Maier SF. 2001. Glial activation: A driving force for pathological pain. Trends Neurosci 24: 450-455.
92. Wu A, Green CR, Rupenthal ID, Moalem-Taylor G. 2012. Role of gap junctions in chronic pain. J Neurosci Res 90: 337-345.
93. Ye ZC, Wyeth MS, Baltan-Tekkok S, Ransom BR. 2003. Functional hemichannels in astrocytes: A novel mechanism of glutamate release. J Neurosci 23: 3588-3596.