The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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Superoxide and Nitric Oxide Involvement in Enhancing of N-methyl-D-aspartate Receptor-Mediated Central Sensitization in the Chronic Post-ischemia Pain Model

  • Ryu, Tae-Ha (Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine) ;
  • Jung, Kyung-Young (Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine) ;
  • Ha, Mi-Jin (Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine) ;
  • Kwak, Kyung-Hwa (Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine) ;
  • Lim, Dong-Gun (Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine) ;
  • Hong, Jung-Gil (Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine)
  • Received : 2009.08.10
  • Accepted : 2009.10.23
  • Published : 2010.03.01
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Abstract

Background: Recent studies indicate that reactive oxygen species (ROS) are involved in persistent pain, including neuropathic and inflammatory pain. Since the data suggest that ROS are involved in central sensitization, the present study examines the levels of activated N-methyl-D-aspartate (NMDA) receptors in the dorsal horn after an exogenous supply of three antioxidants in rats with chronic post-ischemia pain (CPIP). This serves as an animal model of complex regional pain syndrome type-I induced by hindpaw ischemia/reperfusion injury. Methods: The application of tight-fitting O-rings for a period of three hours produced CPIP in male Sprague-Dawley rats. Allopurinol 4 mg/kg, allopurinol 40 mg/kg, superoxide dismutase (SOD) 4,000 U/kg, N-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg and SOD 4,000 U/kg plus L-NAME 10 mg/kg were administered intraperitoneally just after O-ring application and on the first and second days after reperfusion. Mechanical allodynia was measured, and activation of the NMDA receptor subunit 1 (pNR1) of the lumbar spinal cord (L4-L6) was analyzed by the Western blot three days after reperfusion. Results: Allopurinol reduced mechanical allodynia and attenuated the enhancement of spinal pNR1 expression in CPIP rats. SOD and L-NAME also blocked spinal pNR1 in accordance with the reduced mechanical allodynia in rats with CPIP. Conclusions: The present data suggest the contribution of superoxide, produced via xanthine oxidase, and the participation of superoxide and nitric oxide as a precursor of peroxynitrite in NMDA mediated central sensitization. Finally, the findings support a therapeutic potential for the manipulation of superoxide and nitric oxide in ischemia/reperfusion related pain conditions.

Keywords

References

  1. Janig W, Baron R. Complex regional pain syndrome is a disease of the central nervous system. Clin Auton Res 2002; 12: 150-64. https://doi.org/10.1007/s10286-002-0022-1
  2. Coderre TJ, Xanthos DN, Francis L, Bennett GJ. Chronic post-ischemia pain (CPIP): a novel animal model of complex regional pain syndrome-type I (CRPS-I; reflex sympathetic dystrophy) produced by prolonged hindpaw ischemia and reperfusion in the rat. Pain 2004; 112: 94-105. https://doi.org/10.1016/j.pain.2004.08.001
  3. Kwak KH, Han CG, Lee SH, Jeon Y, Park SS, Kim SO, et al. Reactive oxygen species in rats with chronic postischemia pain. Acta Anaesthesiol Scand 2009; 53: 648-56. https://doi.org/10.1111/j.1399-6576.2009.01937.x
  4. Kim HK, Park SK, Zhou JL, Taglialatela G, Chung K, Coggeshall RE, et al. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 2004; 111: 116-24. https://doi.org/10.1016/j.pain.2004.06.008
  5. Hacimuftuoglu A, Handy CR, Goettl VM, Lin CG, Dane S, Stephens RL Jr. Antioxidants attenuate multiple phases of formalin induced nociceptive response in mice. Behav Brain Res 2006; 173: 211-6. https://doi.org/10.1016/j.bbr.2006.06.030
  6. Guedes RP, Bosco LD, Teixeira CM, Araujo AS, Llesuy S, Belló-Klein A, et al. Neuropathic pain modifies antioxidant activity in rat spinal cord. Neurochem Res 2006; 31: 603-9. https://doi.org/10.1007/s11064-006-9058-2
  7. Park ES, Gao X, Chung JM, Chung K. Levels of mitochondrial reactive oxygen species increase in rat neuropathic spinal dorsal horn neurons. Neurosci Lett 2006; 391: 108-11. https://doi.org/10.1016/j.neulet.2005.08.055
  8. Gao X, Kim HK, Chung JM, Chung K. Reactive oxygen species (ROS) are involved in enhancement of NMDAreceptor phosphorylation in animal models of pain. Pain 2007; 131: 262-71. https://doi.org/10.1016/j.pain.2007.01.011
  9. Zou X, Lin Q, Willis WD. Enhanced phosphorylation of NMDA receptor 1 subunits in spinal cord dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats. J Neurosci 2000; 20: 6989-97.
  10. Coderre TJ, Melzack R. The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury. J Neurosci 1992; 12: 3665- 70.
  11. Gao X, Kim HK, Chung JM, Chung K. Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats. Pain 2005; 116: 62-72. https://doi.org/10.1016/j.pain.2005.03.045
  12. Tripatara P, Patel NS, Webb A, Rathod K, Lecomte FM, Mazzon E, et al. Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase. J Am Soc Nephrol 2007; 18: 570-80. https://doi.org/10.1681/ASN.2006050450
  13. Radovic M, Miloradovic Z, Popovic T, Mihailovic-Stanojevic N, Jovovic D, Tomovic M, et al. Allopurinol and enalapril failed to conserve urinary NOx and sodium in ischemic acute renal failure in spontaneously hypertensive rats. Am J Nephrol 2006; 26: 388-99. https://doi.org/10.1159/000094936
  14. Lee WY, Lee SM. Synergistic protective effect of ischemic preconditioning and allopurinol on ischemia/reperfusion injury in rat liver. Biochem Biophys Res Commun 2006; 349: 1087-93. https://doi.org/10.1016/j.bbrc.2006.08.140
  15. Nemeth N, Lesznyak T, Szokoly M, Furka I, Miko I. Allopurinol prevents erythrocyte deformability impairing but not the hematological alterations after limb ischemia reperfusion in rats. J Invest Surg 2006; 19: 47-56. https://doi.org/10.1080/08941930500444511
  16. Albuquerque RG, Sanson AJ, Malangoni MA. Allopurinol protects enterocytes from hypoxia-induced apoptosis in vivo. J Trauma 2002; 53: 415-20. https://doi.org/10.1097/00005373-200209000-00003
  17. Levy D, Zochodne DW. Local nitric oxide synthase activity in a model of neuropathic pain. Eur J Neurosci 1998; 10: 1846-55. https://doi.org/10.1046/j.1460-9568.1998.00186.x
  18. Caban A, Oczkowicz G, Abdel-Samad O, Cierpka L. Influence of ischemic preconditioning and nitric oxide on microcirculation and the degree of rat liver injury in the model of ischemia and reperfusion. Transplant Proc 2006; 38: 196-8. https://doi.org/10.1016/j.transproceed.2005.12.032
  19. Halliwell B, Gutteridge JC. Free radicals in biology and medicine. 4th ed. New York, Oxford University Press. 2007, p 22.
  20. Salvemini D, Riley DP, Lennon PJ, Wang ZQ, Currie MG, Macarthur H, et al. Protective effects of a superoxide dismutase mimetic and peroxynitrite decomposition catalysts in endotoxin-induced intestinal damage. Br J Pharmacol 1999; 127: 685-92. https://doi.org/10.1038/sj.bjp.0702604
  21. Xia ZF, Hollyoak M, Barrow RE, He F, Muller MJ, Herndon DN. Superoxide dismutase and leupeptin prevent delayed reperfusion injury in the rat small intestine during burn shock. J Burn Care Rehabil 1995; 16: 111-7. https://doi.org/10.1097/00004630-199503000-00004
  22. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 2002; 282: C227-41. https://doi.org/10.1152/ajpcell.00112.2001
  23. Kim KW, Ha MJ, Jung KY, Kwak KH, Park SS, Lim DG. Reactive oxygen species and N-methyl-D-aspartate receptor- mediated central sensitization in hindlimb ischemia/ reperfusion injury-induced neuropathic pain rats. Korean J Anesthesiol 2009; 56: 186-94. https://doi.org/10.4097/kjae.2009.56.2.186
  24. Khalil Z, Khodr B. A role for free radicals and nitric oxide in delayed recovery in aged rats with chronic constriction nerve injury. Free Radic Biol Med 2001; 31: 430-9. https://doi.org/10.1016/S0891-5849(01)00597-4
  25. Wang ZQ, Porreca F, Cuzzocrea S, Galen K, Lightfoot R, Masini E, et al. A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther 2004; 309: 869- 78. https://doi.org/10.1124/jpet.103.064154
  26. Schwartz ES, Kim HY, Wang J, Lee I, Klann E, Chung JM, et al. Persistent pain is dependent on spinal mitochondrial antioxidant levels. J Neurosci 2009; 29: 159-68. https://doi.org/10.1523/JNEUROSCI.3792-08.2009
  27. Xu L, Mabuchi T, Katano T, Matsumura S, Okuda-Ashitaka E, Sakimura K, et al. Nitric oxide (NO) serves as a retrograde messenger to activate neuronal NO synthase in the spinal cord via NMDA receptors. Nitric Oxide 2007; 17: 18-24.
  28. Muscoli C, Mollace V, Wheatley J, Masini E, Ndengele M, Wang ZQ, et al. Superoxide-mediated nitration of spinal manganese superoxide dismutase: a novel pathway in Nmethyl- D-aspartate-mediated hyperalgesia. Pain 2004; 111: 96-103. https://doi.org/10.1016/j.pain.2004.06.004
  29. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983; 306: 686-8. https://doi.org/10.1038/306686a0
  30. Masu M, Nakajima Y, Moriyoshi K, Ishii T, Akazawa C, Nakanashi S. Molecular characterization of NMDA and metabotropic glutamate receptors. Ann N Y Acad Sci 1993; 707: 153-64. https://doi.org/10.1111/j.1749-6632.1993.tb38050.x
  31. Mori H, Mishina M. Structure and function of the NMDA receptor channel. Neuropharmacology 1995; 34: 1219-37. https://doi.org/10.1016/0028-3908(95)00109-J
  32. Guix FX, Uribesalgo I, Coma M, Munoz FJ. Physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 2005; 76: 126-52. https://doi.org/10.1016/j.pneurobio.2005.06.001
  33. Zhang XC, Zhang YQ, Zhao ZQ. Different roles of two nitric oxide activated pathways in spinal long-term potentiation of C-fiber-evoked field potentials. Neuropharmacology 2006; 50: 748-54. https://doi.org/10.1016/j.neuropharm.2005.11.021
  34. Duarte ID, dos Santos IR, Lorenzetti BB, Ferreira SH. Analgesia by direct antagonism of nociceptor sensitization involves the arginine-nitric oxide cGMP pathway. Eur J Pharmacol 1992; 217: 225-7. https://doi.org/10.1016/0014-2999(92)90881-4
  35. Ferreira SH, Lorenzetti BB, Faccioli LH. Blockade of hyperalgesia and neurogenic oedema by topical application of nitroglycerin. Eur J Pharmacol 1992; 217: 207-9. https://doi.org/10.1016/0014-2999(92)90871-Z
  36. Bulutcu F, Dogrul A, Guc MO. The involvement of nitric oxide in the analgesic effects of ketamine. Life Sci 2002; 71: 841-53. https://doi.org/10.1016/S0024-3205(02)01765-4
  37. Granados-Soto V, Rufino MO, Gomes Lopes LD, Ferreira SH. Evidence for the involvement of the nitric oxide-cGMP pathway in the antinociception of morphine in the formalin test. Eur J Pharmacol 1997; 340: 177-80. https://doi.org/10.1016/S0014-2999(97)01399-X
  38. Mixcoatl-Zecuatl T, Flores-Murrieta FJ, Granados-Soto V. The nitric oxide-cyclic GMP-protein kinase G-K＋ channel pathway participates in the antiallodynic effect of spinal gabapentin. Eur J Pharmacol 2006; 531: 87-95. https://doi.org/10.1016/j.ejphar.2005.12.006
  39. Ortiz MI, Castro-Olguin J, Pena-Samaniego N, Castaneda- Hernández G. Probable activation of the opioid receptornitric oxide-cyclic GMP-K＋ channels pathway by codeine. Pharmacol Biochem Behav 2005; 82: 695-703. https://doi.org/10.1016/j.pbb.2005.11.011
  40. Ortiz MI, Granados-Soto V, Castaneda-Hernández G. The NO-cGMP-K＋ channel pathway participates in the antinociceptive effect of diclofenac, but not of indomethacin. Pharmacol Biochem Behav 2003; 76: 187-95. https://doi.org/10.1016/S0091-3057(03)00214-4
  41. de Moura RS, Rios AA, Santos EJ, Nascimento AB, de Castro Resende A, Neto ML, et al. Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice. Pharmacol Biochem Behav 2004; 78: 247-53. https://doi.org/10.1016/j.pbb.2004.03.011
  42. Xanthos DN, Bennett GJ, Coderre TJ. Norepinephrineinduced nociception and vasoconstrictor hypersensitivity in rats with chronic post-ischemia pain. Pain 2008; 137: 640-51. https://doi.org/10.1016/j.pain.2007.10.031
  43. Kim YC. Complex regional pain syndrome. Korean J Pain 2004; 17(Suppl): 104-8. https://doi.org/10.3344/kjp.2004.17.S.S104
  44. Milligan ED, Twining C, Chacur M, Biedenkapp J, O'Connor K, Poole S, et al. Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci 2003; 23: 1026-40.
  45. Twining CM, Sloane EM, Milligan ED, Chacur M, Martin D, Poole S, et al. Peri-sciatic proinflammatory cytokines, reactive oxygen species, and complement induce mirror-image neuropathic pain in rats. Pain 2004; 110: 299-309. https://doi.org/10.1016/j.pain.2004.04.008
  46. Gordh T, Sharma HS. Chronic spinal nerve ligation induces microvascular permeability disturbances, astrocytic reaction, and structural changes in the rat spinal cord. Acta Neurochir Suppl 2006; 96: 335-40. https://doi.org/10.1007/3-211-30714-1_70
  47. Light AR, Perl ER. Reexamination of the dorsal root projection to the spinal dorsal horn including observations on the differential termination of coarse and fine fibers. J Comp Neurol 1979; 186: 117-31. https://doi.org/10.1002/cne.901860202
  48. Koltzenburg M, Wall PD, McMahon SB. Does the right side know what the left is doing? Trends Neurosci 1999; 22: 122-7. https://doi.org/10.1016/S0166-2236(98)01302-2
  49. Donaldson LF. Unilateral arthritis: contralateral effects. Trends Neurosci 1999; 22: 495-6.
  50. Kwak KH, Jung KY, Choi JY, Ryu T, Yeo JS, Park SS, et al. Contralateral allodynia and central change in the chronic post-ischemic pain model rats. Korean J Anesthesiol 2009; 56: 419-24. https://doi.org/10.4097/kjae.2009.56.4.419

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