Effects of orally administered OP-1206 α-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model

Abstract

An orally active prostaglandin E1 analogue, OP-1206 α-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis.

To determine whether the OP-1206 α-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 α-CD treatment alone after chronic spinal stenosis in the rat.

Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery.

OP-1206 α-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 α-CD with loxoprofen-Na did not provide additive therapeutical effect.

These results suggest that a significant improvement seen after OP-1206 α-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.