The Journal of Pain
Volume 11, Issue 2 , Pages 131-141 , February 2010

Guanosine Prevents Thermal Hyperalgesia in a Rat Model of Peripheral Mononeuropathy

  • André P. Schmidt

      Affiliations

    • Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • Anesthesia and Perioperative Medicine Service at Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • Corresponding Author InformationAddress reprint requests to Dr André P. Schmidt, Avenida Ramiro Barcelos, 2600-Anexo, 90035-003, Porto Alegre, RS, Brazil.
    • ,
  • Lucas Paniz

      Affiliations

    • Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • ,
  • Cristhine Schallenberger

      Affiliations

    • Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • ,
  • Ana Elisa Böhmer

      Affiliations

    • Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • ,
  • Susana T. Wofchuk

      Affiliations

    • Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • ,
  • Elaine Elisabetsky

      Affiliations

    • Department of Pharmacology, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • ,
  • Luis Valmor C. Portela

      Affiliations

    • Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
    • ,
  • Diogo O. Souza

      Affiliations

    • Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

Received 30 October 2008 ,Revised 29 May 2009 ,Accepted 17 June 2009.

References 

  1. Baron BM, Dudley MW, McCarty DR, Miller FP, Reynolds IJ, Schmidt CJ. Guanine nucleotides are competitive inhibitors of N-Methyl-D-Aspartate at its receptor site both in vitro and in vivo. J Pharmacol Exp Ther. 1989;250:162–169
  2. Bau C, Middlemiss PJ, Hindley S, Jiang S, Ciccarelli R, Caciagli F, et al. Guanosine stimulates neurite outgrowth in PC12 cells via activation of heme oxygenase and cyclic GMP. Purinergic Signal. 2005;1:161–172
  3. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87–107
  4. Binns BC, Huang Y, Goettl VM, Hackshaw KV, Stephens RL. Glutamate uptake is attenuated in spinal deep dorsal and ventral horn in the rat spinal nerve ligation model. Brain Res. 2005;1041:38–47
  5. Burgos JS, Barat A, Souza DO, Ramírez G. Guanine nucleotides protect against kainate toxicity in an ex vivo chick retinal preparation. FEBS Lett. 1998;430:176–180
  6. Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev. 2007;87:659–797
  7. Chang R, Algird A, Bau C, Rathbone MP, Jiang S. Neuroprotective effects of guanosine on stroke models in vitro and in vivo. Neurosci Lett. 2008;431:101–105
  8. Ciccarelli R, Ballerini P, Sabatino G, Rathbone MP, D'Onofrio M, Caciagli F, et al. Involvement of astrocytes in purine-mediated reparative processes in the brain. Int J Dev Neurosci. 2001;19:395–414
  9. Ciccarelli R, Di Iorio P, D'Alimonte I, Giuliani P, Florio T, Caciagli F, et al. Cultured astrocyte proliferation induced by extracellular guanosine involves endogenous adenosine and is raised by the co-presence of microglia. Glia. 2000;29:202–211
  10. Ciccarelli R, Di Iorio P, Giuliani P, D'Alimonte I, Ballerini P, Caciagli F, et al. Rat cultured astrocytes release guanine-based purines in basal conditions and after hypoxia/hypoglycemia. Glia. 1999;25:93–98
  11. Dickenson AH, Suzuki R, Reeve AJ. Adenosine as a potential analgesic target in inflammatory and neuropathic pains. CNS Drugs. 2000;13:77–85
  12. Di Iorio P, Ballerini P, Traversa U, Nicoletti F, D'Alimonte I, Kleywegt S, et al. The antiapoptotic effect of guanosine is mediated by the activation of the PI 3-kinase/AKT/PKB pathway in cultured rat astrocytes. Glia. 2004;46:356–368
  13. Di Iorio P, Caciagli F, Giuliani P, Ballerini P, Ciccarelli R, Sperling O, et al. Purine nucleosides protect injured neurons and stimulate neuronal regeneration by intracellular and membrane receptor-mediated mechanisms. Drug Dev Res. 2001;52:303–315
  14. Dobolyi A, Reichart A, Szikra T, Nyitrai G, Kekesi KA, Juhasz G. Sustained depolarisation induces changes in the extracellular concentrations of purine and pyrimidine nucleosides in the rat thalamus. Neurochem Int. 2000;37:71–79
  15. Domanski L, Sulikowski T, Safranow K, Pawlik A, Olszewska M, Chlubek D, et al. Effect of trimetazidine on the nucleotide profile in rat kidney with ischemia-reperfusion injury. Eur J Pharm Sci. 2006;27:320–327
  16. Fredholm BB. Purines and neutrophil leukocytes. Gen Pharmacol. 1997;28:345–350
  17. Frizzo MES, Lara DR, Dahm KCS, Prokopiuk AS, Swanson R, Souza DO. Activation of glutamate uptake by guanosine in primary astrocyte cultures. Neuroreport. 2001;12:879–881
  18. Frizzo MES, Lara DR, Prokopiuk AS, Vargas CR, Salbego CG, Wajner M, et al. Guanosine enhances glutamate uptake in brain cortical slices at normal and excitotoxic conditions. Cell Mol Neurobiol. 2002;22:353–363
  19. Frizzo MES, Soares FA, Dall'Onder LP, Lara DR, Swanson RA, Souza DO. Extracellular conversion of guanine-based purines to guanosine specifically enhances astrocyte glutamate uptake. Brain Res. 2003;972:84–89
  20. Gebicke-Haerter PJ, Christoffel F, Timmer J, Northoff H, Berger M, Van Calker D. Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation. Neurochem Int. 1996;29:37–42
  21. Gold MS. Spinal nerve ligation: What to blame for the pain and why. Pain. 2000;84:117–120
  22. Gysbers JW, Rathbone MP. Neurite outgrowth in PC12 cells is enhanced by guanosine through both cAMP-dependent and -independent mechanisms. Neurosci Lett. 1996;220:175–178
  23. Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32:77–88
  24. Inoue K, Tsuda M, Koizumi S. ATP receptors in pain sensation: Involvement of spinal microglia and P2X(4) receptors. Purinergic Signal. 2005;1:95–100
  25. Jiang S, Bendjelloul F, Ballerini P, D'Alimonte I, Nargi E, Jiang C, et al. Guanosine reduces apoptosis and inflammation associated with restoration of function in rats with acute spinal cord injury. Purinergic Signal. 2007;3:411–421
  26. Jiang S, Fischione G, Guiliani P, Romano S, Caciagli F, Diiorio P. Metabolism and distribution of guanosine given intraperitoneally: Implications for spinal cord injury. Nucleosides Nucleotides Nucleic Acids. 2008;27:673–680
  27. Jiang S, Khan MI, Lu Y, Wang J, Buttigieg J, Werstiuk ES, et al. Guanosine promotes myelination and functional recovery in chronic spinal injury. Neuroreport. 2003;14:2463–2467
  28. Jongen JL, Haasdijk ED, Sabel-Goedknegt H, Van der Burg J. Vecht ChJ, Holstege JC: Intrathecal injection of GDNF and BDNF induces immediate early gene expression in rat spinal dorsal horn. Exp Neurol. 2005;194:255–266
  29. Jurkowitz MS, Litsky ML, Browning MJ, Hohl CM. Adenosine, inosine, and guanosine protect glial cells during glucose deprivation and mitochondrial inhibition: Correlation between protection and ATP preservation. J Neurochem. 1998;71:535–548
  30. Lara DR, Schmidt AP, Frizzo MES, Burgos JS, Ramirez G, Souza DO. Effect of orally administered guanosine on seizures and death induced by glutamatergic agents. Brain Res. 2001;912:176–180
  31. Litsky ML, Hohl CM, Lucas JH, Jurkowitz MS. Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia. Brain Res. 1999;821:426–432
  32. Malcon C, Achaval M, Komlos F, Partata W, Sauressig M, Ramírez G, et al. GMP protects against quinolinic acid-induced loss of NADPH-diaphorase-positive cells in the rat striatum. Neurosci Lett. 1997;225:145–148
  33. Millan MJ. The induction of pain: An integrative review. Prog Neurobiol. 1997;57:1–164
  34. Peterson GL. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem. 1977;83:346–356
  35. Pettifer KM, Kleywegt S, Bau CJ, Ramsbottom JD, Vertes E, Ciccarelli R, et al. Guanosine protects SH-SY5Y cells against beta-amyloid-induced apoptosis. Neuroreport. 2004;15:833–836
  36. Pezet S, Marchand F, D'Mello R, Grist J, Clark AK, Malcangio M, et al. Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions. J Neurosci. 2008;28:4261–4270
  37. Portela LV, Tort AB, Schaf DV, Ribeiro L, Nora DB, Walz R, et al. The serum S100B concentration is age dependent. Clin Chem. 2002;48:950–952
  38. Rathbone MP, Middlemiss PJ, Gysbers JW, Andrew C, Herman MA, Reed JK, et al. Trophic effects of purines in neurons and glial cells. Prog Neurobiol. 1999;59:663–690
  39. Rathbone M, Pilutti L, Caciagli F, Jiang S. Neurotrophic effects of extracellular guanosine. Nucleosides Nucleotides Nucleic Acids. 2008;27:666–672
  40. Regner A, Ramírez G, Belló-Klein A, Souza DO. Effects of guanine nucleotides on glutamate-induced chemiluminescence in rat hippocampal slices submitted to hypoxia. Neurochem Res. 1998;23:519–524
  41. Roesler R, Vianna MR, Lara DR, Izquierdo I, Schmidt AP, Souza DO. Guanosine impairs inhibitory avoidance performance in rats. Neuroreport. 2000;11:2537–2540
  42. Saute JA, da Silveira LE, Soares FA, Martini LH, Souza DO, Ganzella M. Amnesic effect of GMP depends on its conversion to guanosine. Neurobiol Learn Mem. 2006;85:206–212
  43. Sawynok J. Adenosine receptor activation and nociception. Eur J Clin Pharmacol. 1998;317:1–11
  44. Sawynok J, Liu XJ. Adenosine in the spinal cord and periphery: Release and regulation of pain. Prog Neurobiol. 2003;69:313–340
  45. Schmidt AP, Ávila TT, Souza DO. Intracerebroventricular guanine-based purines protect against seizures induced by quinolinic acid in mice. Neurochem Res. 2005;30:69–73
  46. Schmidt AP, Böhmer AE, Leke R, Schallenberger C, Antunes C, Pereira MS, et al. Antinociceptive effects of intracerebroventricular administration of guanine-based purines in mice: Evidences for the mechanism of action. Brain Res. 2008;1234:50–58
  47. Schmidt AP, Böhmer AE, Schallenberger C, Antunes C, Pereira MS, Leke R, et al. Spinal mechanisms of antinociceptive action caused by guanosine in mice. Eur J Pharmacol. 2009;613:46–53
  48. Schmidt AP, Lara DR, Maraschin JF, Perla AS, Souza DO. Guanosine and GMP prevent seizures induced by quinolinic acid in mice. Brain Res. 2000;864:40–43
  49. Schmidt AP, Lara DR, Souza DO. Proposal of a guanine-based purinergic system in the mammalian central nervous system. Pharmacol Ther. 2007;116:401–416
  50. Soares FA, Schmidt AP, Farina M, Frizzo ME, Tavares RG, Portela LV, et al. Anticonvulsant effect of GMP depends on its conversion to guanosine. Brain Res. 2004;1005:182–186
  51. Souza DO, Ramirez G. Effects of guanine nucleotides in kainic acid binding and on adenylate cyclase activity in chick optic tectum and cerebellum. J Mol Neurosci. 1991;3:39–46
  52. Sung B, Lim G, Mao J. Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J Neurosci. 2003;23:2899–2910
  53. Traversa U, Bombi G, Camaioni E, Macchiarulo A, Costantino G, Palmieri C, et al. Rat brain guanosine binding site: Biological studies and pseudo-receptor construction. Bioorg Med Chem. 2003;11:5417–5425
  54. Traversa U, Bombi G, Di Iorio P, Ciccarelli R, Werstiuk ES, Rathbone MP. Specific [3H]-guanosine binding sites in rat brain membranes. Br J Pharmacol. 2002;135:969–976
  55. Tomaselli B, Podhraski V, Heftberger V, Bock G, Baier-Bitterlich G. Purine nucleoside-mediated protection of chemical hypoxia-induced neuronal injuries involves p42/44 activation. Neurochem Int. 2005;46:513–521
  56. Vinadé ER, Izquierdo I, Lara DR, Schmidt AP, Souza DO. Oral administration of guanosine impairs inhibitory avoidance performance in rats and mice. Neurobiol Learn Mem. 2004;81:137–143
  57. Vinadé ER, Schmidt AP, Frizzo MES, Izquierdo I, Elizabetsky E, Souza DO. Chronically administered guanosine is anticonvulsant, amnesic and anxiolytic in mice. Brain Res. 2003;977:97–102
  58. Vinadé ER, Schmidt AP, Frizzo MES, Portela LV, Soares FA, Schwalm FD, et al. Effects of chronic administered guanosine on behavioral parameters and brain glutamate uptake in rats. J Neurosci Res. 2005;79:248–253
  59. Willis WD. Role of neurotransmitters in sensitization of pain responses. Ann N Y Acad Sci. 2001;933:142–156
  60. Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation: Implications for the treatment of post-injury pain hypersensitivity states. Pain. 1999;44:293–299
  61. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16:109–110

 Supported by the FINEP research grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)” #01.06.0842-00, CNPq, CAPES, FAPERGS, UFRGS.

PII: S1526-5900(09)00606-3

doi: 10.1016/j.jpain.2009.06.010

The Journal of Pain
Volume 11, Issue 2 , Pages 131-141 , February 2010

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