α-Lipoic acid normalizes nociceptive neuronal activity at the spinal cord of diabetic rats

Diabetes Obes Metab. 2011 Aug;13(8):736-41. doi: 10.1111/j.1463-1326.2011.01399.x.

Abstract

Aim: To evaluate the effects of antioxidant treatment of streptozotocin (STZ)-diabetic rats with α-lipoic acid (α-LA) in neuronal and microglial activation at the spinal cord, an important relay station of nociceptive transmission. Because of the role of the potassium chloride co-transporter 2 (KCC2) in neuronal activation at the spinal cord and the influence of microglia in KCC2 expression, we also evaluated the effects of α-LA in KCC2 expression at the spinal cord.

Methods: Four weeks after STZ injection, the rats received daily intraperitoneal injections of α-LA (100 mg/kg), during 2 weeks. Mechanical nociception was evaluated before and after α-LA treatment. Spinal cords were immunoreacted against 8-OH-dG (marker of oxidative stress damage), Fos (marker of neuronal activation) and CD11b (marker of microglia). KCC2 expression was evaluated by immunohistochemistry and western blotting.

Results: Treatment with α-LA decreased the 8-OH-dG and Fos expressions to controls' levels, but did not affect CD11b. Treatment with α-LA alleviated mechanical hyperalgesia and partially corrected KCC2 expression.

Conclusions: This study shows that neuronal hyperactivity at the spinal cord of STZ-diabetic rats can be corrected by α-LA, which may account for alleviation of mechanical hyperalgesia. These effects are probably partially mediated by KCC2, but are independent from microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Male
  • Nociceptors / drug effects*
  • Nociceptors / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Streptozocin
  • Thioctic Acid / metabolism
  • Thioctic Acid / pharmacology*

Substances

  • Antioxidants
  • Streptozocin
  • Thioctic Acid