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Persistent facial pain increases superoxide anion production in the spinal trigeminal nucleus

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Abstract

Previous studies have demonstrated that there is an increase in oxidative stress in the cerebral cortex of rats after repeated painful stimulation and that long-lasting pain increases the production of superoxide ion (O2 ), nitric oxide and peroxynitrite due to the activation of AMPA and NMDA receptors. The purpose of the present study was to evaluate the possible role of O2 in the transmission of oro-facial pain. Formaldehyde 1% was injected subcutaneously into one vibrissal pad of adult male Sprague-Dawley rats as a model of persistent pain, then O2 production and superoxide dismutase (SOD) activity were evaluated in the left and right spinal trigeminal nuclei. O2 production was revealed using dihidroetidium (DHE) injected at 10 or 45 min after the formalin injection in conscious or anaesthetized rats. A histochemical assay for SOD was performed to evaluate the activity of SOD at 10 min after the formalin injection. The results showed a significant increase in O2 production in the homolateral nucleus at 45 min. However, there was no significant difference between the two sides at 10 min after the formalin injection. No significant difference was observed in SOD activity between the two sides of the spinal trigeminal nucleus. This study demonstrated that there is an increased production of O2 in the second phase but not in the first phase of the formalin test; thus O2 is involved in pain induced by inflammation, but not in acute pain.

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References

  1. Breimer L (1991) Repair of DNA damage induced by reactive oxygen species. Free Radic Res Commun 14:159–171

    Article  CAS  PubMed  Google Scholar 

  2. Davies KJA (1993) Protein modification by oxidants and the role of proteolytic enzymes. Biochem Soc Trans 21:346–353

    CAS  PubMed  Google Scholar 

  3. Halliwell B, Chirico S (1993) Lipid peroxidation: its mechanism, measurement and significance. Am J Clin Nutr 57:715–725

    Google Scholar 

  4. Callaghan MJ, Ceradini DJ, Gurtner GC (2005) Hyperglycemia-induced reactive oxygen species and impaired endothelial progenitor cell function. Antioxid Redox Signal 7:1476–1482

    Article  CAS  PubMed  Google Scholar 

  5. Weidig P, McMaster D, Bayraktutan U (2004) High glucose mediates pro-oxidant and antioxidant enzyme activities in coronary endothelial cells. Diabetes Obes Metab 6:432–441

    Article  CAS  PubMed  Google Scholar 

  6. Jackson AL, Loeb LA (2001) The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 477:7–21

    CAS  PubMed  Google Scholar 

  7. Burdon RH (1995) Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med 18:775–794

    Article  CAS  PubMed  Google Scholar 

  8. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40

    Article  CAS  PubMed  Google Scholar 

  9. Adams JD Jr, Odunze IN (1991) Oxygen free radicals and Parkinson’s disease. Free Radic Biol Med 10:161–169

    Article  CAS  PubMed  Google Scholar 

  10. Lovell MA, Markesbery WR (2007) Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease. Nucleic Acids Res 35:7497–7504 (Review)

    Google Scholar 

  11. Barj G (2004) Free radicals and aging. Trends Neurosci 27:595–600

    Article  Google Scholar 

  12. Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10:18–25

    Article  Google Scholar 

  13. Guzik TJ, Sadowski J, Guzik B, Jopek A, Kapelak B, Przybylowski P, Wierzbicki K, Korbut R, Harrison DG, Channon KM (2006) Coronary artery superoxide production and nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol 26:333–339

    Article  CAS  PubMed  Google Scholar 

  14. Loffredo L, Marcoccia A, Pignatelli P, Andreozzi P, Borgia MC, Cangemi R, Chiarotti F, Violi F (2007) Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J 28:608–612

    Article  CAS  PubMed  Google Scholar 

  15. Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581

    CAS  PubMed  Google Scholar 

  16. Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292:18–36

    Google Scholar 

  17. Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312

    Article  CAS  PubMed  Google Scholar 

  18. Ushio-Fukai M, Alexander RW (2004) Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase. Mol Cell Biochem 264:85–97

    Article  CAS  PubMed  Google Scholar 

  19. Colton CA, Fagni L, Gilbert D (1989) The action of hydrogen peroxide on paired pulse and long-term potentiation in the hippocampus. Free Radic Biol Med 7:3–8

    Article  CAS  PubMed  Google Scholar 

  20. Viggiano A, Viggiano E, Monda M, Viggiano A, Ascione S, Amaro S, De Luca B (2007) Intracerebroventricular injection of oxidant and antioxidant molecules affects long-term potentiation in urethane anaesthetized rats. Physiol Res 57:269–273

    PubMed  Google Scholar 

  21. Pellmar TC (1987) Peroxide alters neuronal excitability in the CA1 region of guinea pig hippocampus in vitro. Neuroscience 23:447–456

    Article  CAS  PubMed  Google Scholar 

  22. Auerbach JM, Segal M (1997) Peroxide modulation of slow onset potentiation in rat hippocampus. J Neurosci 17:8695–8701

    CAS  PubMed  Google Scholar 

  23. Rokyta R, Holecek V, Pekárkova I, Krejcová J, Racek J, Trefil L, Yamamotová A (2003) Free radicals after painful stimulation are influenced by antioxidants and analgesics. Neuro Endocrinol Lett 24:304–309

    CAS  PubMed  Google Scholar 

  24. Reiter R, Tang L, Garcia JJ, Muńos-Hoyos A (1997) Pharmacological actions of melatonin in oxygen radical pathophysiology. Life Sci 60:2255–2271

    Article  CAS  PubMed  Google Scholar 

  25. Puig S, Sarkin LS (1995) Formalin-evoked activity in identified primary afferent fibers: systemic lidocaine suppresses phase-2 activity. Pain 64:345–355

    Article  Google Scholar 

  26. Raboisson P, Dallel R (2004) The orofacial formalin test. Neurosci Biobehav Rev 28:219–226

    Article  PubMed  Google Scholar 

  27. Dubuisson D, Dennis SG (1997) The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 4:161–174

    Article  Google Scholar 

  28. Dennis SG, Melzack R (1979) Self-mutilation after dorsal rhizotomy in rats: effects of prior pain and pattern of root lesions. Exp Neurol 65:412–421

    Article  CAS  PubMed  Google Scholar 

  29. Choi HS, Lee HJ, Jung CY, Ju JS, Park JS, Ahn DK (2003) Central cyclooxygenase-2 participates in interleukin-1 beta-induced hyperalgesia in the orofacial formalin test of freely moving rats. Neurosci Lett 352:187–190

    Article  CAS  PubMed  Google Scholar 

  30. Viggiano A, Monda M, Viggiano A, Chiefari M, Aurilio C, De Luca B (2004) Evidence that GABAergic neurons in the spinal trigeminal nucleus are involved in the transmission of inflammatory pain in the rat: a microdialysis and pharmacological study. Eur J Pharmacol 496:87–92

    Article  CAS  PubMed  Google Scholar 

  31. Azerad J, Woda A, Albe-Fessard D (1982) Physiological properties of neurons in different parts of the cat trigeminal sensory complex. Brain Res 246:7–21

    Article  CAS  PubMed  Google Scholar 

  32. Dallel R, Raboisson P, Woda A, Sessle BJ (1990) Properties of nociceptive and non-nociceptive neurons in trigeminal subnucleus oralis of the rat. Brain Res 521:95–106

    Article  CAS  PubMed  Google Scholar 

  33. Dubner R, Bennett GJ (1983) Spinal and trigeminal mechanisms of nociception. Annu Rev Neurosci 6:381–418 (Review)

    Google Scholar 

  34. Viggiano A, Monda M, Viggiano Al, Viggiano D, Viaggiano E, Chiefari M, Ausilio C, De Luca B (2005) Trigeminal pain transmission requires reactive oxygen species production. Brain Res 1050:72–78

    Article  CAS  PubMed  Google Scholar 

  35. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates (2nd edn). Academic Press, New York

    Google Scholar 

  36. Tal M (1996) A novel antioxidant alleviates heat hyperalgesia in rats with an experimental painful peripheral neuropathy. Neuroreport 7:1382–1384

    Article  CAS  PubMed  Google Scholar 

  37. Salvemini D, Wang ZQ, Zweier JL, Samouilov A, Macarthur H, Misko TP, Currie MG, Cuzzocrea S, Sikorski JA, Riley DP (1999) A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science 286:304–306

    Article  CAS  PubMed  Google Scholar 

  38. Kim HK, Park SK, Zhou JL, Taglialatela G, Chung K, Coggeshall RE, Chung JM (2004) Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 111:116–124

    Article  CAS  PubMed  Google Scholar 

  39. Wang ZQ, Porreca F, Cuzzocrea S, Galen K, Lightfoot R, Masini E, Muscoli C, Mollace V, Ndengele M, Ischiropoulos H, Salvemini D (2004) A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther 309:869–878

    Article  CAS  PubMed  Google Scholar 

  40. Kim HK, Kim JH, Gao X, Zhou JL, Lee I, Chung K, Chung JM (2006) Analgesic effect of vitamin E is mediated by reducing central sensitization in neuropathic pain. Pain 122:53–62

    Article  CAS  PubMed  Google Scholar 

  41. Woolf CJ, Thompson SWN (1991) The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation; implication for the treatment of post-injury pain hypersensitivity states. Pain 44:293–299

    Article  CAS  PubMed  Google Scholar 

  42. Dubner R, Ruda MA (1992) Activity-dependent neuronal plasticity following tissue injury and inflammation. Trends Neurosci 15:96–103

    Article  CAS  PubMed  Google Scholar 

  43. Coderre TJ, Melzack R (1992) The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury. J Neurosci 12:3665–3670

    CAS  PubMed  Google Scholar 

  44. Ren K, Hylden JLK, Williams GM, Ruda MA, Dubner R (1992) The effects of a non-competitive NMDA receptor antagonist, MK-801, on behavioral hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation. Pain 50:331–344

    Article  CAS  PubMed  Google Scholar 

  45. Ma QP, Woolf CJ (1996) Progressive tactile hypersensitivity: an inflammation-induced incremental increase in the excitability of the spinal cord. Pain 67:97–106

    Article  CAS  PubMed  Google Scholar 

  46. Cerne R, Jiang M, Randic M (1992) Cyclic adenosine 3′5′-monophosphate potentiates excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons. Brain Res 596:111–123

    Article  CAS  PubMed  Google Scholar 

  47. Li P, Zhuo M (1998) Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature 393:695–698

    Article  CAS  PubMed  Google Scholar 

  48. Christie JM, Wenthold RJ, Monaghan DT (1999) Insulin causes a transient tyrosine phosphorylation of NR2A and NR2B NMDA receptor subunits in rat hippocampus. J Neurochem 72:1523–1528

    Article  CAS  PubMed  Google Scholar 

  49. Gao X, Kim HK, Chung JM, Chung K (2005) Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats. Pain 116:62–72

    Article  CAS  PubMed  Google Scholar 

  50. Gao X, Kim HK, Chung JM, Chung K (2007) Reactive oxygen species (ROS) are involved in enhancement of NMDA-receptor phosphorylation in animal models of pain. Pain 131:262–271

    Article  CAS  PubMed  Google Scholar 

  51. Klann E, Roberson ED, Knapp LT, Sweatt JD (1998) A role for superoxide in protein kinase C activation and induction of long-term potentiation. J Biol Chem 273:4516–4522

    Article  CAS  PubMed  Google Scholar 

  52. Li L, Shou Y, Borowitz JL, Isom GE (2001) Reactive oxygen species mediate pyridostigmine-induced neuronal apoptosis: involvement of muscarinic and NMDA receptors. Toxicol Appl Pharmacol 177:17–25

    Article  CAS  PubMed  Google Scholar 

  53. Kim HY, Wang J, Lu Y, Chung JM, Chung K (2009) Superoxide signaling in pain is independent of nitric oxide signaling. Neuroreport 20:1424–1428

    Article  CAS  PubMed  Google Scholar 

  54. Doyle T, Bryant L, Batinic-Haberle I, Little J, Cuzzocrea S, Masini E, Spasojevic I, Salvemini D (2009) Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance. Neurosci 164:702–710

    Article  CAS  Google Scholar 

  55. Muscoli C, Mollace V, Wheatley J, Masini E, Ndengele M, Wang ZQ, Salvemini D (2004) Superoxide-mediated nitration of spinal manganese superoxide dismutase: a novel pathway in N-methyl-d-aspartate-mediated hyperalgesia. Pain 111:96–103

    Article  CAS  PubMed  Google Scholar 

  56. Dalo NL, Larson AA (1990) Effects of urethane and ketamine on substance P- and excitatory amino acid-induced behavior in mice. Eur J Pharmacol 184:173–177

    Article  CAS  PubMed  Google Scholar 

  57. Salo DC, Pacifici RE, Lin SW, Giulivi C, Davies KJA (1990) Superoxide dismutase undergoes proteolysis and fragmentation following oxidative modification and inactivation. J Biol Chem 256:11919–11927

    Google Scholar 

  58. Viggiano A, Viggiano D, Viggiano A, De Luca B (2003) Quantitative histochemical assay for superoxide dismutase in rat brain. J Histochem Cytochem 51:865–871

    CAS  PubMed  Google Scholar 

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Viggiano, E., Monda, M., Viggiano, A. et al. Persistent facial pain increases superoxide anion production in the spinal trigeminal nucleus. Mol Cell Biochem 339, 149–154 (2010). https://doi.org/10.1007/s11010-009-0378-9

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