Skip to main content

Advertisement

Log in

Diabetic Peripheral Neuropathy: Role of Reactive Oxygen and Nitrogen Species

  • Review Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The prevalence of diabetes has reached epidemic proportions. There are two forms of diabetes: type 1 diabetes mellitus is due to auto-immune-mediated destruction of pancreatic β-cells resulting in absolute insulin deficiency and type 2 diabetes mellitus is due to reduced insulin secretion and or insulin resistance. Both forms of diabetes are characterized by chronic hyperglycemia, leading to the development of diabetic peripheral neuropathy (DPN) and microvascular pathology. DPN is characterized by enhanced or reduced thermal, chemical, and mechanical pain sensitivities. In the long-term, DPN results in peripheral nerve damage and accounts for a substantial number of non-traumatic lower-limb amputations. This review will address the mechanisms, especially the role of reactive oxygen and nitrogen species in the development and progression of DPN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Amos, A., Mccarty, D., & Zimmet, P. (1997). The rising global burden of diabetes and its complications estimates and projections to the year 2010. Diabetic Medicine, 14, S1–S85.

    PubMed  Google Scholar 

  2. King, H., Auber, R., & Herman, W. (1998). Global burden of diabetes, 1995–2025. Prevalence, numerical estimates and projections. Diabetes Care, 21, 1414–1431.

    PubMed  CAS  Google Scholar 

  3. World Health Organisation. (1999). Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Geneva: Department of noncommunicable disease surveillance.

  4. The Diabetes Control and Complications Trial Research Group. (1993). The effect of Intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England Journal of Medicine, 329, 977–986.

    Google Scholar 

  5. UK Prospective Diabetes Study (UKPDS) Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. (UKPDS 33). Lancet, 1998(352), 837–853.

    Google Scholar 

  6. Edwards, J. L., Vincent, A. M., & Cheng, H. T. (2008). Feldman EL Diabetic neuropathy: Mechanisms to management. Pharmacology & Therapeutics, 120, 1–34.

    CAS  Google Scholar 

  7. Sherrington, C. S. (1906). The integrative action of the nervous system. New Haven, CT: Yale University Press.

    Google Scholar 

  8. Burgess, P. R., & Perl, E. R. (1967). Myelinated afferent fibres responding specifically to noxious stimulation of the skin. Journal of Physiology, 190, 541–562.

    PubMed  CAS  Google Scholar 

  9. Djouhri, L., Bleazard, L., & Lawson, S. N. (1998). Association of somatic action potential shape with sensory receptive properties in guinea-pig dorsal root ganglion neurones. Journal of Physiology, 513, 857–872.

    PubMed  CAS  Google Scholar 

  10. Schmidt, R., Schmelz, M., Forster, C., Ringkamp, M., Torebjork, E., & Handwerker, H. (1995). Novel classes of responsive and unresponsive C nociceptors in human skin. Journal of Neuroscience, 15, 333–341.

    PubMed  CAS  Google Scholar 

  11. Vinik, A. I., Holland, M. T., Le Beau, J. M., Liuzzi, F. J., Stansberry, K. B., & Colen, L. B. (1992). Diabetic neuropathies. Diabetes Care, 15, 1926–1975.

    PubMed  CAS  Google Scholar 

  12. Sima, A. A., Thomas, P. K., Ishii, D., & Vinik, A. (1997). Diabetic neuropathies. Diabetologia, 40, B74–B77.

    PubMed  Google Scholar 

  13. Ramji, N., Toth, C., Kennedy, J., & Zochodne, D. W. (2007). Does diabetes mellitus target motor neurons? Neurobiology of Diseases, 26, 301–311.

    CAS  Google Scholar 

  14. Zochodne, D. W., Ramji, N., & Toth, C. (2008). Neuronal targeting in diabetes mellitus: A story of sensory neurons and motor neurons. Neuroscientist, 14, 311–318.

    PubMed  CAS  Google Scholar 

  15. Schmader, K. E. (2002). Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. Clinical Journal of Pain, 18, 350–354.

    PubMed  Google Scholar 

  16. Laudadio, C., & Sima, A. A. (2006). Progression rates of diabetic neuropathy in placebo patients in an 18-month clinical trial, Ponalrestat Study Group. Journal of Diabetes Complications, 12, 121–127.

    Google Scholar 

  17. Said, G., Slama, G., & Selva, J. (1983). Progressive centripetal degeneration of axons in small fibre diabetic polyneuropathy. Brain, 106, 791–807.

    PubMed  Google Scholar 

  18. Said, G., Goulon-Goeau, C., Slama, G., & Tchobroutsky, G. (1992). Severe early-onset polyneuropathy in insulin-dependent diabetes mellitus. A clinical and pathological study. The New England Journal of Medicine, 326, 1257–1263.

    PubMed  CAS  Google Scholar 

  19. Pinzur, M. S. (2002). The diabetic foot. Comprehensive Therapy, 28, 232–237.

    PubMed  Google Scholar 

  20. Dworkin, R. H., O’Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jensen, T. S., et al. (2007). Pharmacologic management of neuropathic pain: Evidence-based recommendations. Pain, 132, 237–251.

    PubMed  CAS  Google Scholar 

  21. Aley, K. O., & Levine, J. D. (2001). Rapid onset pain induced by intravenous streptozotocin in the rat. Journal of Pain, 2, 146–150.

    PubMed  CAS  Google Scholar 

  22. Chu, Q., Moreland, R., Yew, N. S., Foley, J., Ziegler, R., & Scheule, R. K. (2008). Systemic insulin-like growth factor-1 reverses hypoalgesia and improves mobility in a mouse model of diabetic peripheral neuropathy. Molecular Therapy, 16, 1400–1408.

    PubMed  CAS  Google Scholar 

  23. Vareniuk, I., Pavlov, I. A., & Obrosova, I. G. (2008). Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocin-induced mouse model of diabetes. Diabetologia, 51, 2126–2133.

    PubMed  CAS  Google Scholar 

  24. Oltman, C. L., Davidson, E. P., Coppey, L. J., Kleinschmidt, T. L., Lund, D. D., Adebara, E. T., et al. (2008). Vascular and neural dysfunction in Zucker diabetic fatty rats: A difficult condition to reverse. Diabetes, Obesity & Metabolism, 10, 64–74.

    CAS  Google Scholar 

  25. Pabbidi, R. M., Yu, S. Q., Peng, S., Khardori, R., Pauza, M. E., & Premkumar, L. S. (2008). Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity. Molecular Pain, 1, 4–9.

    Google Scholar 

  26. Cameron, N. E., Eaton, S. E., & Tesfaye, S. (2001). Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia, 44, 1973–1988.

    PubMed  CAS  Google Scholar 

  27. Glanni, C., & Dyck, P. J. (1995). Basement membrane thickening and pericyte degeneration precede development of diabetic polyneuropathy and are associated with its severity. Annals of Neurology, 37, 498–504.

    Google Scholar 

  28. Britland, S. T., Young, R. J., & Sharma, A. K. (1990). Relationship of endoneurial capillary abnormalities to type and severity of diabetic neuropathy. Diabetes, 39, 909–913.

    PubMed  CAS  Google Scholar 

  29. Timpereley, W. R., Ward, J. D., & Preston, F. E. (1977). Clinical and histological studies in diabetic neuropathy. Diabetologia, 12, 237–243.

    Google Scholar 

  30. Sheetz, M. J., & King, Gl. (2002). Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA, 288, 2579–2588.

    PubMed  CAS  Google Scholar 

  31. Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813–820.

    PubMed  CAS  Google Scholar 

  32. Wimalawansa, S. J. (1996). Calcitonin gene-related peptide: Molecular genetics, physiology, pathology and therapeutic potentials. Endocrinology Reviews, 1996(17), 533–585.

    Google Scholar 

  33. Belai, I. A., & Burnstock, G. (1987). Selective damage of intrinsic calcitonin gene-related peptide-like immunoreactive enteric nerve fibers in streptozotocin-induced diabetic rats. Gastroenterology, 92, 730–734.

    PubMed  CAS  Google Scholar 

  34. Rittenhouse, P. A., Marchand, I. E., Chen, J., Kream, R. M., & Leeman, S. E. (1995). Streptozotocin-induced diabetes is associated with altered expression of peptide-encoding mRNA in rat sensory neurons. Peptides, 17, 1017–1022.

    Google Scholar 

  35. Bennett, G. J., & Xie, Y. K. (1988). A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain, 33, 87–107.

    PubMed  CAS  Google Scholar 

  36. Sheykhzade, M., Dalsgaard, G. T., Johansen, T., & Nyborg, N. C. B. (2000). The effect of long-term streptozotocin-induced diabetes on contractile and relaxation responses of coronary arteries: Selective attenuation of CGRP-induced relaxations. British Journal of Pharmacology, 129, 1212–1218.

    PubMed  CAS  Google Scholar 

  37. Wilson, D. K., Bohren, K. M., Gabbay, K. K., & Quiocho, F. A. (1992). An unlikely sugar substrate site in the 1.65 Å structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science, 257, 81–84.

    PubMed  CAS  Google Scholar 

  38. Lee, A. Y., & Chung, S. S. (1999). Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB Journal, 13, 23–30.

    PubMed  CAS  Google Scholar 

  39. Thornalley, P. J. (1990). The glyoxalase system: New developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochemical Journal, 269, 1–11.

    PubMed  CAS  Google Scholar 

  40. Hammes, H. P., Du, X., Edelstein, D., Taguchi, T., Matsumura, T., Ju, Q., et al. (2003). Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nature Medicine, 9, 294–299.

    PubMed  CAS  Google Scholar 

  41. Sugimoto, K., Murakawa, Y., & Sima, A. A. (2000). Diabetic neuropathy a continuing enigma. Diabetes Metabolism Research and Reviews, 16, 408–433.

    PubMed  CAS  Google Scholar 

  42. Way, K. J., Katai, N., & King, G. L. (2001). Protein kinase C and the development of diabetic vascular complications. Diabetic Medicine, 18, 945–959.

    PubMed  CAS  Google Scholar 

  43. Eicheberg, J. (2002). Protein kinase C changes in diabetes: Is the concept relevant to neuropathy? International Review of Neurobiology, 50, 61–82.

    Google Scholar 

  44. Roberts, R. E., & McClean, W. G. (1997). Protein kinase C isozyme expression in sciatic nerves and spinal cords of experimentally diabetic rats. Brain Research, 754, 147–156.

    PubMed  CAS  Google Scholar 

  45. Yamagishi, S., Uehara, K., Otsuki, S., & Yagihashi, S. (2003). Differential influence of increased polyol pathway on protein kinase C expressions between endoneurial and epineurial tissues in diabetic mice. Journal of Neurochemistry, 87, 497–507.

    PubMed  CAS  Google Scholar 

  46. Shiba, T., Inoguchi, T., Sportman, J. R., Heath, W., Bursell, S., & King, G. L. (1993). Correlation of diacylglycerol and protein kinase C activity in rat retina to retinal circulation. American Journal of Physiology, 265, E783–E793.

    PubMed  CAS  Google Scholar 

  47. Craven, P. A., & DeRubertis, F. R. (1989). Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose. Journal of Clinical Investigation, 83, 1667–1675.

    PubMed  CAS  Google Scholar 

  48. Nakamura, K. K., Hamada, Y., Nakayama, M., Chaya, S., Nakashima, E., Naruse, K., et al. (1999). A protein kinase C-[beta]-selective inhibitor ameliorates neural dysfunction in streptozocin-induced diabetic rats. Diabetes, 48, 2090–2095.

    PubMed  CAS  Google Scholar 

  49. Sasase, T., Yamada, H., Sakoda, K., Imagawa, N., Abe, T., Ito, M., et al. (2005). Novel protein kinase C-beta isoform selective inhibitor JTT-010 ameliorates both hyper- and hypoalgesia in streptozotocin- induced diabetic rats. Diabetes, Obesity & Metabolism, 7, 586–594.

    CAS  Google Scholar 

  50. Kom-Litty, V., Sauer, U., Nerlich, A., Lehmann, R., & Schelicher, E. D. (1998). High glucose-induced transforming growth factor beta 1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. Journal of Clinical Investigation, 101, 160–169.

    Google Scholar 

  51. Du, X. L., Edelstein, D., Dimmeler, S., Qida, J., Sui, C., & Brownlee, M. (2001). Hyperglycemia inhibits endothelial nitric oxide synthase activity by post translational modification at the AKT site. Journal of Clinical Investigation, 108, 1341–1348.

    PubMed  CAS  Google Scholar 

  52. Nishikawa, T., Edelstein, D., Xl, Du., Yamagishi, S., Matsumura, T., Kaneda, Y., et al. (2000). Normalising mitochondrial superoxide production blocks three pathways of hyperglycemic damage. Nature, 2000(404), 787–790.

    Google Scholar 

  53. Korshunov, S. S., Skulachev, V. P., & Starkov, A. A. (1997). High protonic potential actuates a mechanism production of reactive oxygen species in mitochondria. FEBS Letters, 416, 15–18.

    PubMed  CAS  Google Scholar 

  54. Harman, D. (1956). Aging: A theory based on free radical and radiation chemistry. Journals of Gerontology, 11, 298–300.

    PubMed  CAS  Google Scholar 

  55. Deby, C., & Gouter, R. (1990). New perspectives on the biochemistry of superoxide anion and the efficacy of superoxide dismutases. Biochemical Pharmacology, 39, 399–405.

    PubMed  CAS  Google Scholar 

  56. Fridovich, I. (1978). The biology of oxygen radicals. Science, 201, 875–880.

    PubMed  CAS  Google Scholar 

  57. Jensen, M. P., & Riley, D. P. (2002). Peroxynitrite decomposition activity of iron porphyrin complexes. Inorganic Chemistry, 41, 4788–4797.

    PubMed  CAS  Google Scholar 

  58. Ushio-Fukai, M., Alexander, R. W., Akers, M., & Griendling, K. K. (1998). p38 MAP kinase is a critical component of the redox-sensitive signaling pathways by angiotensin II: Role in vascular smooth muscle cell hypertrophy. Journal of Biological Chemistry, 273, 15022–15029.

    PubMed  CAS  Google Scholar 

  59. Barchowsky, A., Munro, S. R., Morana, S. J., Vincenti, M. P., & Treadwell, M. (1995). Oxidant-sensitive and phosphorylation-dependent activation of NF-kappa B and AP-1 in endothelial cells. American Journal of Physiology, 269, 829–836.

    Google Scholar 

  60. Tan, S., Sagara, Y., Liu, Y., Maher, P., & Schubert, D. (1998). The regulation of reactive oxygen species production during programmed cell death. Journal of Cell Biology, 141, 1423–1432.

    PubMed  CAS  Google Scholar 

  61. Johnson, T. M., Yu, Z. X., Ferrans, V. J., Lowenstein, R. A., & Finkel, T. (1996). Reactive oxygen species are downstream mediators of p53-dependent apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 21, 11848–11852.

    Google Scholar 

  62. Arvidson B. (1979). Distribution of protein tracers in peripheral ganglia. A light and electron microscopic study in rodents after various modes of tracer administration. Acta Universitatis Upsaliensis, 344, 1–72.

    Google Scholar 

  63. Zochodne, D. W., Verge, V. M. K., Cheng, C., Hong, S., & Johnston, J. (2001). Does diabetes target ganglion neurones? Brain, 124, 2319–2334.

    PubMed  CAS  Google Scholar 

  64. Anand, P., Terenghi, G., Warnere, G., Kopelman, P., Williams-Chestnut, R. E., & Sinicropi, D. V. (1996). The role of endogenous growth factor in human diabetic neuropathy. Nature Medicine, 2, 703–707.

    PubMed  CAS  Google Scholar 

  65. Lewin, G. R., & Mendell, L. M. (1993). Nerve growth factor and nociception. Trends in Neurosciences, 16, 353–359.

    PubMed  CAS  Google Scholar 

  66. Kishi, M., Tanabe, J., Schmelzer, J. D., & Low, P. A. (2002). Morphometry of dorsal root ganglion in chronic experimental diabetic neuropathy. Diabetes, 51, 819–824.

    PubMed  CAS  Google Scholar 

  67. Schmeichel, A. M., Schmelzer, J. D., & Low, P. A. (2003). Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes, 52, 165–171.

    PubMed  CAS  Google Scholar 

  68. Srinivasan, S., Stevens, M., & Wiley, J. W. (2000). Diabetic peripheral neuropathy. Evidence for apoptosis and associated mitochondrial dysfunction. Diabetes, 11, 1932–1938.

    Google Scholar 

  69. Vincent, A. M., Olzmann, J. A., Brownlee, M., Sivitz, W. I., & Russell, J. W. (2004). Uncoupling proteins prevent glucose-induced neuronal oxidative stress and programmed cell death. Diabetes, 53, 726–734.

    PubMed  CAS  Google Scholar 

  70. Geilen, C. C., Wieprecht, M., & Orfansos, C. E. (1996). The mitogen-activated protein kinases system (MAP kinase cascade): Its role in skin signal transduction: A review. Journal of Dermatological Science, 12, 255–262.

    PubMed  CAS  Google Scholar 

  71. Tomlinson, D. R., & Gardiner, N. J. (2008). Glucose neurotoxicity. Nature Reviews Neuroscience, 9, 36–45.

    PubMed  CAS  Google Scholar 

  72. Cantoni, O., Boscoboinik, D., Fiorani, M., Staule, B., & Azzi, A. (1996). The phoshorylation state of MAP-kinases modulates the cytotoxic response of smooth muscle cells to hydrogen peroxide. FEBS Letters, 389, 285–288.

    PubMed  CAS  Google Scholar 

  73. Elbirt, K. K., Whitmarsh, A. J., Davis, R. J., & Bonkovsky, H. L. (1998). Mechanism of sodium arsenite-mediated induction of heme oxygenase-1 in hepatoma cells: Role mitogen-activated protein kinases. Journal of Biological Chemistry, 273, 8922–8931.

    PubMed  CAS  Google Scholar 

  74. Purves, T., Middlemas, A., Agthong, S., Jude, E. B., Andrew, J. M., Boulton, A. J., et al. (2001). A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy. FASEB Journal, 15, 2508–2514.

    PubMed  CAS  Google Scholar 

  75. Ji, R., Samad, T. A., Jin, S. X., Schmoll, R., & Wooolf, C. J. (2002). P38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains hyperalgesia. Neuron, 36, 57–68.

    PubMed  CAS  Google Scholar 

  76. Svensson, S. I., Fitzsimmons, B., Azizi, S., Powell, H. C., Hua, H. Y., & Yaksh, T. L. (2005). Spinal p38beta isoform mediates tissue injury-induced hyperalgesia and spinal sensitization. Journal of Neurochemistry, 92, 1508–1520.

    PubMed  CAS  Google Scholar 

  77. Turk, J., Corbett, J. A., Ramanadham, S., Bohrer, A., & McDaniel, L. (1993). Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochemical and Biophysical Research Communications, 197, 1458–1464.

    PubMed  CAS  Google Scholar 

  78. Nukatsuka, M., Yoshimura, Y., Nishida, M., & Kawada, J. (1990). Allopurinol protects pancreatic beta cells from the cytotoxic effect of streptozotocin in vitro study. Journal of Pharmacobio-Dynamics, 13, 259–262.

    PubMed  CAS  Google Scholar 

  79. Sofue, M., Yoshimura, Y., Nishida, M., & Kawada, J. (1991). Uptake of nicotinamide by rat pancreatic beta cells with regard to streptozotocin action. Journal of Endocrinology, 13, 135–138.

    Google Scholar 

  80. Suzukawa, K., Miura, K., Mitsushita, J., Resau, J., Hirose, K., Crystal, R., & Kamata, T. (2000). Nerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species. J Biol Chem, 275(18), 13175–13178.

    Google Scholar 

  81. Pabbidi, R. M., Cao, D. S., Parihar, A., Pauza, M. E., & Premkumar, L. S. (2008). Direct role of streptozotocin in inducing thermal hyperalgesia by enhanced expression of TRPV1 in sensory neurons. Molecular Pharmacology, 73, 995–1004.

    PubMed  CAS  Google Scholar 

  82. Puntambekar, P., Mukherjea, D., Jajoo, S., & Ramkumar, V. (2005). Essential role of Rac1/NADPH oxidase in nerve growth factor induction of TRPV1 expression. Journal of Neurochemistry, 95, 1689–1703.

    PubMed  CAS  Google Scholar 

  83. Angel, P., & Karin, M. (1991). The role of jun, fos and the AP-1 complex in cell proliferation and transformation. Biochimica et Biophysica Acta, 1072, 129–157.

    PubMed  CAS  Google Scholar 

  84. Devary, Y., Gottlieb, R. A., Laus, L. F., & Karin, M. (1991). Rapid and preferential activation of the c-jun gene during the mammalian UV response. Molecular and Cellular Biology, 11, 2804–2811.

    PubMed  CAS  Google Scholar 

  85. Meyer, M., Schreck, R., & Baeuerle, P. A. (1993). H2O2 and antioxidants have opposite effects on activation of NF-kB and AP-1 in intact cells: AP-1 as secondary antioxidant response factor. EMBO Journal, 12, 2005–2015.

    PubMed  CAS  Google Scholar 

  86. Schmidt, R. E., Dorsey, D. A., Beaudet, L. N., & Peterson, R. G. (2003). Analysis of the zucker diabetic fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy. American Journal of Pathology, 163, 21–28.

    PubMed  CAS  Google Scholar 

  87. Chattopadhyay, M., Mata, M., Goss, J., Wolfe, D., Huang, S., Glorioso, J. C., et al. (2007). Prolonged preservation of nerve function in diabetic neuropathy in mice by herpes simplex virus-mediated gene transfer. Diabetologia, 50, 1550–1558.

    PubMed  CAS  Google Scholar 

  88. Ieda, M., Kanazawa, H., Ieda, Y., Kimura, K., Matsumura, K., Tomita, Y., et al. (2006). Nerve growth factor is critical for cardiac sensory innervation and rescues neuropathy in diabetic hearts. Circulation, 114, 2351–2363.

    PubMed  CAS  Google Scholar 

  89. Roux, P. P., & Blenis, J. (2004). ERK and p38 MAPK-activated protein kinases: A family of protein kinases with diverse biological functions. Microbiology and Molecular Biology Reviews, 68, 320–344.

    PubMed  CAS  Google Scholar 

  90. Tomlinson, D. R., & Gardiner, N. J. (2008). Diabetic neuropathies: Components of etiology. Journal of the Peripheral Nervous System, 13, 112–121.

    PubMed  CAS  Google Scholar 

  91. Premkumar, L. S., & Ahern, G. P. (2000). Induction of vanilloid receptor channel activity by protein kinase C. Nature, 408, 985–990.

    PubMed  CAS  Google Scholar 

  92. Van Buren, J. J., Bhat, S., Rotello, R., Pauza, M. E., & Premkumar, L. S. (2005). Sensitization and translocation of TRPV1 by insulin and IGF-I. Molecular Pain, 1, 17.

  93. Hong, S., & Wiley, J. W. (2005). Early painful diabetic neuropathy is associated with differential changes in the expression and function of vanilloid receptor 1. Journal of Biological Chemistry, 280, 618–627.

    PubMed  CAS  Google Scholar 

  94. Kamei, J., Zushida, K., Mortia, K., Sasaki, M., & Tanaka, S. (2001). Role of vanilloid VR1 receptor in thermal allodynia and hyperalgesia in diabetic mice. European Journal of Pharmacology, 422, 83–86.

    PubMed  CAS  Google Scholar 

  95. Rashid, M. H., Inoue, M., Kondo, S., Kawashima, T., Bakoshi, S., & Ueda, H. (2003). Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin cream in neuropathic pain. Journal of Pharmacology and Experimental Therapeutics, 304, 940–948.

    PubMed  CAS  Google Scholar 

  96. Julius, D., & Basbaum, A. I. (2001). Molecular mechanisms of nociception. Nature, 413, 203–210.

    PubMed  CAS  Google Scholar 

  97. Woolf, C. J., & Salter, M. W. (2000). Neuronal plasticity: Increasing the gain in pain. Science, 288, 1765–1769.

    PubMed  CAS  Google Scholar 

  98. Nordin, M., Nystrom, B., Wallin, U., & Hagbarth, K. E. (1984). Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves, dorsal roots and dorsal columns. Pain, 20, 231–245.

    PubMed  CAS  Google Scholar 

  99. Wall, P. D., & Gutnick, M. (1994). Ongoing activity in peripheral nerves: The physiology and pharmacology of impulses originating from a neuroma. Experimental Neurology, 43, 580–589.

    Google Scholar 

  100. Wall, P. D., & Devor, M. (1983). Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve ligated rats. Pain, 17, 321–339.

    PubMed  CAS  Google Scholar 

  101. Matzner, O., & Devor, M. (1994). Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. Journal of Neurophysiology, 72, 349–359.

    PubMed  CAS  Google Scholar 

  102. Janig, W., Levine, J. D., & Michaelis, M. (1996). Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma. Progress in Brain Research, 113, 161–184.

    PubMed  CAS  Google Scholar 

  103. Ramer, M. S., & Bisby, M. A. (1997). Rapid sprouting of sympathetic axons in dorsal root ganglia of rats with a chronic constriction injury. Pain, 70, 237–244.

    PubMed  CAS  Google Scholar 

  104. Goswami, C., & Hucho, T. (2007). TRPV1 expression-dependent initiation and regulation of filopodia. Journal of Neurochemistry, 103, 1319–1333.

    PubMed  CAS  Google Scholar 

  105. Maggi, C. A., & Meli, A. (1988). The sensory-efferent function of capsaicin-sensitive neurons. General Pharmacology, 19, 1–43.

    PubMed  CAS  Google Scholar 

  106. McDonald, D. M., Bowden, J. J., Baluk, P. P., & Bunnett, N. W. (1996). Neurogenic inflammation. A model for studying efferent actions of sensory nerves. Advances in Experimental Medicine and Biology, 410, 453–462.

    PubMed  CAS  Google Scholar 

  107. Moreau, M. E., Garbacki, N., Molinaro, G., Brown, N. J., Marceau, F., & Adam, A. (2005). The kallikrein–kinin system: Current and future pharmacological targets. Journal of Pharmacological Sciences, 99, 6–38.

    PubMed  CAS  Google Scholar 

  108. Wang, H., Kohno, T., Amaya, F., Brenner, G. J., Ito, N., Allchorne, A., et al. (2005). Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission. Journal of Neuroscience, 25, 7986–7992.

    PubMed  CAS  Google Scholar 

  109. Zahner, M. R., Li, D. P., Chen, S. R., & Pan, H. L. (2003). Cardiac vanilloid receptor 1-expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats. Journal of Physiology, 551, 515–523.

    PubMed  CAS  Google Scholar 

  110. Seyedi, N., Maruyama, R., & Levi, R. (1999). Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: A novel mechanism of ischemic norepinephrine release? Journal of Pharmacology and Experimental Therapeutics, 290, 656–663.

    PubMed  CAS  Google Scholar 

  111. Suzuki, R., & Dickenson, A. (2005). Spinal and supraspinal contributions to central sensitization in peripheral neuropathy. Neurosignals, 14, 175–181.

    PubMed  CAS  Google Scholar 

  112. Lauria, G., Morbin, M., Lombardi, R., Capobianco, R., Camozzi, F., Pareyson, D., et al. (2006). Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies. Journal of the Peripheral Nervous System, 11, 262–271.

    PubMed  CAS  Google Scholar 

  113. Facer, P., Casula, M. A., Smith, G. D., Benham, C. D., Chessell, I. P., Bountra, C., et al. (2007). Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy. BMC Neurology, 7, 11.

    PubMed  Google Scholar 

  114. Kawamata, M., & Omote, K. (1996). Involvement of increased excitatory amino acids and intracellular Ca2+ concentration in the spinal dorsal horn in an animal model of neuropathic pain. Pain, 68, 85–96.

    PubMed  CAS  Google Scholar 

  115. Rabben, T., Skjelbred, P., & Oye, I. (1999). Prolonged analgesic effect of ketamine, an N-methyl-d-aspartate receptor inhibitor, in patients with chronic pain. Journal of Pharmacology and Experimental Therapeutics, 289, 1060–1066.

    PubMed  CAS  Google Scholar 

  116. Stiller, C. O., Cui, J. G., O’Connor, W. T., Brodin, E., Meyerson, B. A., & Linderoth, B. (1996). Release of gamma-aminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord stimulation in mononeuropathic rats. Neurosurgery, 39, 367–374.

    PubMed  CAS  Google Scholar 

  117. Zeilhofer, H. U. (2005). The glycinergic control of spinal pain processing. Cellular and Molecular Life Sciences, 62, 2027–2035.

    PubMed  CAS  Google Scholar 

  118. Leenders, A. G., & Sheng, Z. H. (2005). Modulation of neurotransmitter release by the second messenger-activated protein kinases: Implications for presynaptic plasticity. Pharmacology & Therapeutics, 105, 69–84.

    CAS  Google Scholar 

  119. Premkumar, L. S., Qi, Z. H., Van Buren, J., & Raisinghani, M. (2004). Enhancement of potency and efficacy of NADA by PKC-mediated phosphorylation of vanilloid receptor. Journal of Neurophysiology, 91, 1442–1449.

    PubMed  CAS  Google Scholar 

  120. Premkumar, L. S., Raisinghani, M., Pingle, S. C., Long, C., & Pimentel, F. (2005). Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation. Journal of Neuroscience, 25, 11322–11329.

    PubMed  CAS  Google Scholar 

  121. Premkumar, L. S., & Sikand, P. (2008). TRPV1: A target for next generation analgesics. Current Opinion in Pharmacology, 6, 151–163.

    CAS  Google Scholar 

  122. Jeffry, J. A., Yu, S. Q., Sikand, P., Parihar, A., Evans, M. S., & Premkumar, L. S. (2009). Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia. PLoS One, 4, e7021.

    PubMed  Google Scholar 

  123. Lindsay, T. J., Rodgers, B. C., Savath, V., & Hettinger, K. (2010). Treating diabetic peripheral neuropathic pain. American Family Physician, 82, 151–158.

    PubMed  Google Scholar 

  124. Wong, M. C., Chung, J. W., & Wong, T. K. (2007). Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ, 335(7610), 87.

    PubMed  CAS  Google Scholar 

  125. Argoff, C. E., Backonja, M. M., & Belgrade, M. J., et al. (2006). Diabetic peripheral neuropathic pain: Consensus guidelines for treatment. Mayo Clinic Proceedings, 81(4 Suppl), S12–S25.

    Google Scholar 

  126. Saarto, T., & Wiffen, P. J. (2007). Antidepressants for neuropathic pain. Cochrane Database of Systematic Reviews, 4, CD005454.

  127. Vinik, A. (2005). Clinical review: Use of antiepileptic drugs in the treatment of chronic painful diabetic neuropathy. Journal of Clinical Endocrinology and Metabolism, 90, 4936–4945.

    PubMed  CAS  Google Scholar 

  128. Freeman, R., Durso-Decruz, E., & Emir, B. (2008). Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: Findings from seven randomized, controlled trials across a range of doses. Diabetes Care, 31, 1448–1454.

    PubMed  CAS  Google Scholar 

  129. Wernicke, J. F., Pritchett, Y. L., D’Souza, D. N., et al. (2006). A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology, 67, 1411–1420.

    PubMed  CAS  Google Scholar 

  130. Eisenberg, E., McNicol, E., & Carr, D. B. (2003). Opioids for neuropathic pain. Cochrane Database of Systematic Reviews, 3, CD006146.

  131. Hollingshead, J., Dühmke, R. M., & Cornblath, D. R. (2006). Tramadol for neuropathic pain. Cochrane Database of Systematic Reviews, 3, CD003726.

  132. Harati, Y., Gooch, C., Swenson, M., et al. (1998). Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology, 50, 1842–1846.

    PubMed  CAS  Google Scholar 

  133. Mason, L., Moore, R. A., Derry, S., Edwards, J. E., & McQuay, H. J. (2004). Systematic review of topical capsaicin for the treatment of chronic pain. BMJ, 328, 991.

    PubMed  CAS  Google Scholar 

  134. Meier, T., Wasner, G., Faust, M., et al. (2003). Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: A randomized, double-blind, placebo-controlled study. Pain, 106, 151–158.

    PubMed  CAS  Google Scholar 

  135. Sima, A. A., Calvani, M., Mehra, M., Amato, A., & Acetyl-l-Carnitine Study Group. (2005). Acetyl-l-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: An analysis of two randomized placebo-controlled trials. Diabetes Care, 28, 89–94.

    PubMed  CAS  Google Scholar 

  136. Ametov, A. S., Barinov, A., Dyck, P. J., et al. (2003). SYDNEY Trial Study Group. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: The SYDNEY trial. Diabetes Care, 26, 770–776. (published correction appears in Diabetes Care 2003;26:2227).

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the National Institutes of Health (DK065742 and DA028017).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Louis S. Premkumar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Premkumar, L.S., Pabbidi, R.M. Diabetic Peripheral Neuropathy: Role of Reactive Oxygen and Nitrogen Species. Cell Biochem Biophys 67, 373–383 (2013). https://doi.org/10.1007/s12013-013-9609-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-013-9609-5

Keywords

Navigation