OP-1206, A PROSTAGLANDIN E(1), DERIVATIVE, ATTENUATES THE THERMAL HYPERESTHESIA INDUCED BY CONSTRICTION INJURY TO THE SCIATIC-NERVE IN THE RAT

Nerve ischemia induces wallerian degeneration and peripheral neuropath y, and nerve constriction injury induces thermal hyperesthesia. Nerve ischemia is one possible mechanism in the development of thermal hyper esthesia in the nerve constriction injury model. Prostaglandin E(1) in creases tissue blood flow. In the present study, the authors examine t he role of nerve ischemia in the maintenance of the thermal hyperesthe sia induced by nerve constriction injury by orally administering OP-12 06, a prostaglandin E(1) derivative. A nerve constriction injury model was created by making four loose ligations around the rat sciatic ner ve, which induces thermal hyperesthesia in the ligated paw in 2-5 days . OP-1206, was administered six times (Day 7, one time; Day 8, two tim es; Day 9, two times; Day 10, one time). A single administration of OP -1206 had no effect on the thermal hyperesthesia. Six hours after the sixth-administration of OP-1206, the level of the thermal hyperesthesi a was attenuated in a dose-dependent manner, and this effect lasted mo re than 1 day after the last drug administration. These data indicate that nerve ischemia plays an important role in maintaining the thermal hyperesthesia induced by nerve constriction injury in the rat.