DIFFERENT EFFECTS OF 2 ALDOSE REDUCTASE INHIBITORS ON NOCICEPTION ANDPROSTAGLANDIN-E

This study examined the effect of two structurally dissimilar aldose r eductase inhibitors, ethoxy-1-napthalenyl]thioxomethyl]-N-methlyglycin e (tolrestat) and 4-amino-2,6-dimethylphenyl-sulphonyl nitromethane (I CI 222155), on formalin-evoked behavioural responses in control and di abetic rats and on capsaicin-evoked release of prostaglandin E from sp inal cord slices in vitro. Both compounds, given orally for 4 weeks, p revented hyperalgesia in diabetic rats 5-20 min after hindpaw formalin injection. ICI 222155 also prevented hyperalgesia in diabetic rats 21 -60 min after formalin, whereas tolrestat suppressed activity in diabe tic rats below controls and also suppressed activity in controls when given orally or intrathecally. Capsaicin-evoked release of prostagland in E from spinal cord slices of control rats was significantly reduced by tolrestat, but not ICI 222155. These data suggest that hyperalgesi a in diabetic rats is related to glucose metabolism by aldose reductas e, whereas tolrestat has specific effects on formalin-evoked nocicepti on associated with an ability to reduce spinal prostaglandin release.