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Investigation of effects of neurotrophic factors on painful diabetic neuropathy: an experimental study

Year 2019, Volume: 5 Issue: 4, 641 - 648, 04.07.2019
https://doi.org/10.18621/eurj.414105

Abstract

Objective: We have studied the effects of neurotrophin-4 (NT-4)
different doses on the pain levels of streptozocin-induced diabetic rats.



Methods: Thirty-five 3-week-old male rats were used. After
induction of diabetes in rats with streptozocin (nearly 4 weeks); diabetic
animals were divided into 4 groups. The first group; healthy control group (n =
15 ), the second group; diabetic control group ( n = 10 ), the third group; low
dose (0.3 mg/ kg ) recombinant human NT-4 was applied ( n = 4 ) and the fourth
group; high dose recombinant human NT-4 was applied (n = 6).



Results: In the low-dose NT-4 group, the pain threshold values
did not differ from the diabetic control and healthy control groups. In the
high dose NT-4 group, a rise was observed in the pain threshold values of hot
plate in comparison with the healthy control group, diabetic control group and
low dose applied group and this rise reached at the level of statistical
significance (p < 0.05).



Conclusion: Neurotrophic factors (neurotrophin-4) have been shown
to be effective on painful diabetic neuropathy in streptozocin-induced diabetic
rats. However, there is a need for larger-scale and longer-term studies for
clinical use. 

References

  • [1] Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum. Indian J Endocrinol Metab 2016;20:546-51.
  • [2] Davon A. M, Chronic pain. A primary Care Guide to Practical Management, second ed., Human Pres: Totawa, NJ. 2005;114-5.
  • [3] Price RD, Milne SA, Sharkey J, Matsuoka N, Advances in small molecules promoting neurotrophic function. Pharmacol Ther 2007;115:292-306.
  • [4] Bennett DL. Neurotrophic factors important regulators of nociceptive function. Neuroscientist 2001;7:13-7.
  • [5] Skaper SD. The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol 2012;846:1-12.
  • [6] Kerr BJ, Bradbury EJ, Bennett DL, Trivedi PM, Dassan P, French J, et al. Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord. J Neurosci 1999;19:5138-48.
  • [7] Chen SQ, Cai Q, Shen YY, Cai XY, Lei HY. Combined use of NGF/BDNF/bFGF promotes proliferation and differentiation of neural stem cells in vitro. Int J Dev Neurosci 2014;38:74-8.
  • [8] Christianson JA, Ryals JM, McCarson KE, Wright DE. Beneficial actions of neurotrophin therapy on diabetes-induced hypoalgesia in mice. J Pain 2003;4:493-504.
  • [9] Christianson JA, Ryals JM, Johnson MS , Dobrowsky RT, Wright DE. Neurotrophic modulation of myelinated cutaneous innervation and mechanical sensory loss in diabetic mice. Neuroscience 2007;145:303-13.
  • [10] Handwerker HO, Kobal G. Psychophysiology of experimentally induced pain. Physiol Rev 1993;73:639-71.
  • [11] Deli G, Bosecyak E, Pusch G, Komoly S, Feher G. Diabetic neuropathies: diagnosis and management. Neuroendocrinology 2013;98:267-80.
  • [12] Vinik AI, Park TS, Stansberry K B, Pittenger GL. Diabetic neuropathies. Diabetologia 2000;43;957-73.
  • [13] Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol 2002;11:521-34.
  • [14] Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabet Med 2005;22:359-70.
  • [15] Malik RA. Current and future strategies for the management of diabetic neuropathy. Treat Endocrinol 2003;2:389-400.
  • [16] Ahlgren SC, Levine JD. Mechanical hyperlgesia in streptozocin diabetic rat is not sympathetically maintained. Brain Res 1993;616:171-5.
  • [17] Ahlgren SC, White DM, Levine JD. Increased responsiveness of sensory neurons in the saphenous nerve of the streptozotocin-diabetic rat. J Neurophysiol 1992;68:2077-85.
  • [18] Piercy V, Banner SE, Bhattacharyya A, Parsons AA, Sanger GJ, Smith SA, et al. Thermal but not mechanical, nociceptive behavior is altered in the Zucker Diabetic Fatty rat and is independent of glycemic status. J Diabetes Complications 1999;13:163-9.
  • [19] Zhuang HX, Secyder CK, Pu SF, Ishii DN. Insulin-like growth factors reverse or arrest diabetic neuropathy: effects on hyperalgesia and impaired nerve regeneration in rats. Exp Neurol 1996;140:198-205.
  • [20] Calcutt NA, Jorge MC, Yaksh TL, Chaplan SR. Tactile allodynia and formalin hyperalgesia in streptozotocin-diabetic rats: effects of insulin, aldose reductase inhibition and lidocaine. Pain 1996;68 293-9.
  • [21] Fox A, Eastwood C, Gentry C, Manning D, Urban L. Critical evaluation of the streptozotocin model in the rat. Pain 1999;81:307-16.
  • [22] Raz I, Hasdai D, Seltzer M, Melmed RN. Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats. Diabetes 1988;37:1253-9.
  • [23] Klitgaard H, Matagne A, Gobert J, Wülfert E. Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. Eur J Pharmacol 1998;353:191-206.
  • [24] Apfel SC. Neurotrophic factors in the therapy of diabetic neuropathy. Am J Med 2000;107:34-42.
  • [25] Schuman EM. Neurotropin regulation of synaptic transmission. Curr Opin Neurobiol 1999;9:105-9.
  • [26] Apfel SC. Neurotrophic factors and diabetic peripheral neuropathy. Eur Neurol 1999;41:27-34.
  • [27] Akkina SK, Patterson CL, Wright DE. GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice. Exp Neurol 2001;167:173-82.
  • [28] Apfel SC, Kessler JA. Neurotrophic factors in the therapy of peripheral neuropathy, Baillieres Clin Neurol 1995;4:593-606.
  • [29] Wellmer A, Misra VP, Sharief MK, Kopelman PG, Anand P. A double-blind placebo-controlled clinical trial of recombinant human brain-derived neurotrophic factor (rhBDNF) in diabetic polyneuropathy. J Peripher Nerv Syst 2001;6:204-10.
  • [30] Siuciak JA, Wong V, Pearsall D, Wiegand SJ, Lindsay RM. BDNF produces analgesia in the formalin test and modifies neuropeptide levels in rat brain and spinal cord areas associated with nociception. Eur J Neurosci 1995;7663-70.
Year 2019, Volume: 5 Issue: 4, 641 - 648, 04.07.2019
https://doi.org/10.18621/eurj.414105

Abstract

References

  • [1] Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum. Indian J Endocrinol Metab 2016;20:546-51.
  • [2] Davon A. M, Chronic pain. A primary Care Guide to Practical Management, second ed., Human Pres: Totawa, NJ. 2005;114-5.
  • [3] Price RD, Milne SA, Sharkey J, Matsuoka N, Advances in small molecules promoting neurotrophic function. Pharmacol Ther 2007;115:292-306.
  • [4] Bennett DL. Neurotrophic factors important regulators of nociceptive function. Neuroscientist 2001;7:13-7.
  • [5] Skaper SD. The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol 2012;846:1-12.
  • [6] Kerr BJ, Bradbury EJ, Bennett DL, Trivedi PM, Dassan P, French J, et al. Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord. J Neurosci 1999;19:5138-48.
  • [7] Chen SQ, Cai Q, Shen YY, Cai XY, Lei HY. Combined use of NGF/BDNF/bFGF promotes proliferation and differentiation of neural stem cells in vitro. Int J Dev Neurosci 2014;38:74-8.
  • [8] Christianson JA, Ryals JM, McCarson KE, Wright DE. Beneficial actions of neurotrophin therapy on diabetes-induced hypoalgesia in mice. J Pain 2003;4:493-504.
  • [9] Christianson JA, Ryals JM, Johnson MS , Dobrowsky RT, Wright DE. Neurotrophic modulation of myelinated cutaneous innervation and mechanical sensory loss in diabetic mice. Neuroscience 2007;145:303-13.
  • [10] Handwerker HO, Kobal G. Psychophysiology of experimentally induced pain. Physiol Rev 1993;73:639-71.
  • [11] Deli G, Bosecyak E, Pusch G, Komoly S, Feher G. Diabetic neuropathies: diagnosis and management. Neuroendocrinology 2013;98:267-80.
  • [12] Vinik AI, Park TS, Stansberry K B, Pittenger GL. Diabetic neuropathies. Diabetologia 2000;43;957-73.
  • [13] Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol 2002;11:521-34.
  • [14] Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabet Med 2005;22:359-70.
  • [15] Malik RA. Current and future strategies for the management of diabetic neuropathy. Treat Endocrinol 2003;2:389-400.
  • [16] Ahlgren SC, Levine JD. Mechanical hyperlgesia in streptozocin diabetic rat is not sympathetically maintained. Brain Res 1993;616:171-5.
  • [17] Ahlgren SC, White DM, Levine JD. Increased responsiveness of sensory neurons in the saphenous nerve of the streptozotocin-diabetic rat. J Neurophysiol 1992;68:2077-85.
  • [18] Piercy V, Banner SE, Bhattacharyya A, Parsons AA, Sanger GJ, Smith SA, et al. Thermal but not mechanical, nociceptive behavior is altered in the Zucker Diabetic Fatty rat and is independent of glycemic status. J Diabetes Complications 1999;13:163-9.
  • [19] Zhuang HX, Secyder CK, Pu SF, Ishii DN. Insulin-like growth factors reverse or arrest diabetic neuropathy: effects on hyperalgesia and impaired nerve regeneration in rats. Exp Neurol 1996;140:198-205.
  • [20] Calcutt NA, Jorge MC, Yaksh TL, Chaplan SR. Tactile allodynia and formalin hyperalgesia in streptozotocin-diabetic rats: effects of insulin, aldose reductase inhibition and lidocaine. Pain 1996;68 293-9.
  • [21] Fox A, Eastwood C, Gentry C, Manning D, Urban L. Critical evaluation of the streptozotocin model in the rat. Pain 1999;81:307-16.
  • [22] Raz I, Hasdai D, Seltzer M, Melmed RN. Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats. Diabetes 1988;37:1253-9.
  • [23] Klitgaard H, Matagne A, Gobert J, Wülfert E. Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. Eur J Pharmacol 1998;353:191-206.
  • [24] Apfel SC. Neurotrophic factors in the therapy of diabetic neuropathy. Am J Med 2000;107:34-42.
  • [25] Schuman EM. Neurotropin regulation of synaptic transmission. Curr Opin Neurobiol 1999;9:105-9.
  • [26] Apfel SC. Neurotrophic factors and diabetic peripheral neuropathy. Eur Neurol 1999;41:27-34.
  • [27] Akkina SK, Patterson CL, Wright DE. GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice. Exp Neurol 2001;167:173-82.
  • [28] Apfel SC, Kessler JA. Neurotrophic factors in the therapy of peripheral neuropathy, Baillieres Clin Neurol 1995;4:593-606.
  • [29] Wellmer A, Misra VP, Sharief MK, Kopelman PG, Anand P. A double-blind placebo-controlled clinical trial of recombinant human brain-derived neurotrophic factor (rhBDNF) in diabetic polyneuropathy. J Peripher Nerv Syst 2001;6:204-10.
  • [30] Siuciak JA, Wong V, Pearsall D, Wiegand SJ, Lindsay RM. BDNF produces analgesia in the formalin test and modifies neuropeptide levels in rat brain and spinal cord areas associated with nociception. Eur J Neurosci 1995;7663-70.
There are 30 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Articles
Authors

Faruk Kılınç 0000-0002-0198-2558

Ramis Çolak 0000-0001-8323-0781

Mete Özcan This is me 0000-0002-5551-4880

Ahmet Ayar 0000-0002-9449-9564

Publication Date July 4, 2019
Submission Date April 10, 2018
Acceptance Date June 11, 2018
Published in Issue Year 2019 Volume: 5 Issue: 4

Cite

AMA Kılınç F, Çolak R, Özcan M, Ayar A. Investigation of effects of neurotrophic factors on painful diabetic neuropathy: an experimental study. Eur Res J. July 2019;5(4):641-648. doi:10.18621/eurj.414105

e-ISSN: 2149-3189 


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