Display options
Cite
Sun Y, Yang PP, Song ZY, et al. α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats. J Pain Res. 2017;10:1645-1655doi: 10.2147/JPR.S135017.
Sun, Y., Yang, P. P., Song, Z. Y., Feng, Y., Hu, D. M., Hu, J., Xu, G. Y., & Zhang, H. H. (2017). α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats. Journal of pain research, 101645-1655. https://doi.org/10.2147/JPR.S135017
Sun, Yan, et al. "α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats." Journal of pain research vol. 10 (2017): 1645-1655. doi: https://doi.org/10.2147/JPR.S135017
Sun Y, Yang PP, Song ZY, Feng Y, Hu DM, Hu J, Xu GY, Zhang HH. α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats. J Pain Res. 2017 Jul 14;10:1645-1655. doi: 10.2147/JPR.S135017. eCollection 2017. PMID: 28769585; PMCID: PMC5529097.
Copy Download .nbib Format: NLM
Share it on

J Pain Res. 2017 Jul 14;10:1645-1655. doi: 10.2147/JPR.S135017. eCollection 2017.

α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats.

Journal of pain research

Yan Sun, Pan-Pan Yang, Zhen-Yuan Song, Yu Feng, Duan-Min Hu, Ji Hu, Guang-Yin Xu, Hong-Hong Zhang

Affiliations

  1. Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
  2. Department of Endocrinology, The East District of Suzhou Municipal Hospital, Suzhou, People's Republic of China.
  3. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, People's Republic of China.

PMID: 28769585 PMCID: PMC5529097 DOI: 10.2147/JPR.S135017

Abstract

AIM: Patients with long-standing diabetes often demonstrate intestinal dysfunction, characterized as constipation or colonic hypersensitivity. Our previous studies have demonstrated the roles of voltage-gated sodium channels NaV1.7 and NaV1.8 in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. This study was designed to determine roles of antioxidant α-lipoic acid (ALA) on sodium channel activities and colonic hypersensitivity of rats with diabetes.

METHODS: Streptozotocin was used to induce diabetes in adult female rats. Colonic sensitivity was measured by behavioral responses to colorectal distention in rats. The excitability and sodium channel currents of colon projection DRG neurons labeled with DiI were measured by whole-cell patch-clamp recordings. The expressions of NaV1.7 and NaV1.8 of colon DRGs were measured by western blot analysis.

RESULTS: ALA treatment significantly increased distention threshold in responding to colorectal distension in diabetic rats compared with normal saline treatment. ALA treatment also hyper-polarized the resting membrane potentials, depolarized action potential threshold, increased rheobase, and decreased frequency of action potentials evoked by ramp current stimulation. Furthermore, ALA treatment also reduced neuronal sodium current densities of DRG neurons innervating the colon from rats with diabetes. In addition, ALA treatment significantly downregulated NaV1.7 and NaV1.8 expression in colon DRGs from rats with diabetes.

CONCLUSION: Our results suggest that ALA plays an analgesic role, which was likely mediated by downregulation of NaV1.7 and NaV1.8 expressions and functions, thus providing experimental evidence for using ALA to treat colonic hypersensitivity in patients with diabetic visceral pain.

Keywords: colonic hypersensitivity; diabetes; dorsal root ganglion; voltage-gated sodium channels; α-lipoic acid

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

References

  1. Eur Rev Med Pharmacol Sci. 2012 Jan;16(1):66-78 - PubMed
  2. Gut. 2008 Sep;57(9):1230-7 - PubMed
  3. J Neurosci. 2013 May 22;33(21):9028-38 - PubMed
  4. Saudi Pharm J. 2016 Sep;24(5):547-553 - PubMed
  5. Mol Pain. 2011 Aug 18;7:60 - PubMed
  6. J Investig Med. 2011 Apr;59(4):649-54 - PubMed
  7. AACN Clin Issues. 2004 Jan-Mar;15(1):136-49 - PubMed
  8. Diabetes Care. 2013 Nov;36(11):3698-705 - PubMed
  9. Neurosci Bull. 2016 Oct;32(5):445-54 - PubMed
  10. J Neurogastroenterol Motil. 2016 Jan 31;22(1):129-40 - PubMed
  11. Diabetes. 2011 Jun;60(6):1743-51 - PubMed
  12. J Neuroinflammation. 2014 Mar 07;11:45 - PubMed
  13. Schizophr Res. 2015 Jul;165(2-3):163-70 - PubMed
  14. Gastroenterology. 2007 Feb;132(2):615-27 - PubMed
  15. Nature. 2000 Apr 13;404(6779):787-90 - PubMed
  16. Handb Exp Pharmacol. 2014;223:767-94 - PubMed
  17. Diabetes. 1997 Sep;46 Suppl 2:S62-6 - PubMed
  18. Neurobiol Aging. 2002 Sep-Oct;23(5):819-34 - PubMed
  19. Neurochem Res. 2007 Nov;32(11):1990-2001 - PubMed
  20. Eur J Pain. 2014 Feb;18(2):162-73 - PubMed
  21. Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1184-9 - PubMed
  22. World J Gastroenterol. 2006 Sep 21;12(35):5611-21 - PubMed
  23. Neurogastroenterol Motil. 2008 Apr;20(4):349-57 - PubMed
  24. J Allergy Clin Immunol. 2004 Aug;114(2):429-35 - PubMed
  25. Mol Pain. 2009 Aug 06;5:44 - PubMed
  26. Exp Physiol. 1997 Mar;82(2):291-5 - PubMed
  27. Neurogastroenterol Motil. 2011 Feb;23(2):131-8, e26 - PubMed
  28. Toxicol Appl Pharmacol. 2002 Jul 1;182(1):84-90 - PubMed
  29. Neuroscience. 2013 Mar 1;232:64-73 - PubMed
  30. Brain Res. 1997 Feb 28;749(2):188-99 - PubMed
  31. Ann N Y Acad Sci. 2005 Jun;1043:440-51 - PubMed
  32. Eur J Clin Invest. 1984 Dec;14(6):420-7 - PubMed
  33. Brain Res. 2016 May 15;1639:174-85 - PubMed
  34. Redox Biol. 2014 Jun 02;2:702-14 - PubMed
  35. Clin Biochem. 2015 Jun;48(9):581-5 - PubMed
  36. Mol Pain. 2012 Dec 18;8:89 - PubMed
  37. Nat Med. 2012 Jun;18(6):926-33 - PubMed
  38. Int J Exp Pathol. 2011 Dec;92(6):400-12 - PubMed
  39. Nutrition. 2001 Oct;17(10):888-95 - PubMed
  40. Physiol Behav. 2016 Jul 1;161:15-23 - PubMed
  41. PLoS One. 2012;7(12):e53165 - PubMed
  42. CNS Neurosci Ther. 2013 Feb;19(2):83-90 - PubMed
  43. Eur Rev Med Pharmacol Sci. 2014;18(18):2766-71 - PubMed
  44. Am J Gastroenterol. 1987 Jan;82(1):29-35 - PubMed
  45. Neurochem Int. 2014 Sep;75:112-9 - PubMed
  46. Neurosci Bull. 2012 Apr;28(2):155-64 - PubMed
  47. Adv Drug Deliv Rev. 2008 Oct-Nov;60(13-14):1463-70 - PubMed

Publication Types