Ameliorative potential of spironolactone in diabetes induced hyperalgesia in mice

Abstract

The present study was designed to investigate the ameliorative potential of spironolactone against diabetic hyperalgesia in mice. Tail flick latency, an index of hyperalgesia, was assessed by analgesiometer. Serum nitrite levels, an index of nitric oxide, were analyzed by Griess reaction. Mice were rendered diabetic with streptozotocin (200 mg kg-1 i.p) and kept for 30 days for development of diabetic pain. Thereafter, spleen homogenate supernatant (SHS) was prepared from the mouse spleen and administered in normal mice for 14 days. In both diabetic and SHS-treated mice a significant degree of hyperalgesia was developed, suggesting the key role of spleen-derived factor in induction of diabetic pain. Moreover, the levels of nitric oxide were also elevated in 30th day diabetic mice and SHS-treated mice. Administration of spironolactone (7 and 15 mg kg-1 p.o.) significantly attenuated diabetes-induced decrease of nociceptive threshold and increase of serum nitrite oxide levels. Furthermore, SHS of spironolactone-treated diabetic mice failed to induce hyperalgesia and to increase serum nitrite levels. These results suggest that spironolactone has ameliorative potential in attenuating the hyperalgesia associated with diabetes, which may be possibly mediated through inhibition of release of certain critical factors from spleen. © 2009 The Pharmaceutical Society of Japan.