RP-67580, a specific tachykinin NK1 receptor antagonist, relieves chronic hyperalgesia in diabetic rats

The effect of a non-peptide NK1 receptor antagonist, RP-67580, and of its enantiomer, RP-68651, on nociceptive thresholds in normal and streptozocin-induced diabetic rats submitted to paw pressure is reported. RP-67580 (1, 3, 9 mg/kg s.c.) dose dependently reduced the diabetes-induced mechanical hyperalgesia observed 4 weeks after induction of diabetes. In normal rats, RP-67580 failed to increase nociceptive thresholds. RP-68651 was inactive in both diabetic and normal rats. These results suggest that (i) substance P is involved in the diabetes-induced chronic hyperalgesia, and (ii) NK1 receptor antagonists merit to be studied more extensively in relation with this pathological condition.