The influence of indomethacin and guanethidine on experimental streptozotocin diabetic neuropathy

Can J Neurol Sci. 1992 Nov;19(4):433-41.

Abstract

In diabetic animals, reduced endoneurial perfusion and oxygen content have been linked to neuropathic abnormalities and might be amenable to pharmacological manipulation. In streptozotocin-induced diabetic rats, we studied the influence of guanethidine adrenergic sympathectomy, indomethacin treatment and a combined strategy on: serial in vivo motor and sensory conduction, resistance to ischemic conduction failure, in vitro myelinated and unmyelinated conduction, endoneurial perfusion and endoneurial oxygen tension. Unlike previous work diabetic animals had normal endoneurial perfusion but lower endoneurial oxygen tensions after six months of hyperglycemia. Guanethidine worsened sensory conduction despite lower microvascular resistance and an improvement in endoneurial oxygen tension. In contrast, indomethacin improved motor and sensory conduction but not oxygen tension. These studies do not support a linkage between conduction deficits and early endoneurial microangiopathy in experimental diabetes. Indomethacin, or related agents may offer a new therapeutic approach toward diabetic neuropathy through a mechanism independent of the endoneurial microvasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / physiopathology
  • Guanethidine / therapeutic use*
  • Indomethacin / therapeutic use*
  • Male
  • Neural Conduction / drug effects
  • Oxygen / blood
  • Peripheral Nerves / blood supply
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / drug effects

Substances

  • Oxygen
  • Indomethacin
  • Guanethidine