Diabetic neuropathy in the rat: 1. Alcar augments the reduced levels and axoplasmic transport of substance P

This study examined the sciatic nerve axonal transport of substance P‐like immunoreactivity (SPLI) and its basal content in stomach, sciatic nerve and lumbar spinal cord of 8‐ and 12‐week alloxan‐diabetic rats, respectively. One group of diabetic rats received acetyl‐l‐carnitine (ALCAR) throughout the experimental period. Alloxan treatment caused hyperglycemia and reduced body growth. Axonal transport of SPLI was studied by measurement of 24‐hour accumulation at a ligature on the sciatic nerve. There was a marked reduction (from 50% to 100% according to the nerve segment examined) of anterograde and retrograde accumulation of SPLI in the constricted nerve of 8‐week diabetic rats. In the sciatic nerve of ALCAR‐treated diabetic rats, the accumulation of SPLI was comparable to control values. In the sciatic nerve, lumbar spinal cord and stomach of 12‐week diabetic rats, there is a significant reduction of SPLI content. ALCAR treatment prevented SPLI loss in these tissues. Sciatic nerves showed the typical sorbitol increase and myo‐inositol loss that were significantly counteracted by ALCAR. This study suggests that ALCAR treatment prevents diabetes‐induced sensory neuropathy by improving altered metabolic pathways such as polyol activity and myo‐inositol synthesis, and by preventing the reduction of synthesis and axonal transport of substance P. © 1995 Wiley‐Liss, Inc.