• Anesthesia and analgesia · Jun 2002

    The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model.

    • Katsuhiko Nakai, Yoshifumi Takenobu, Kazuhide Eguchi, Hideyuki Takimizu, Kaneyoshi Honjo, Shinji Akimaru, Hitoshi Maegawa, Martin Marsala, and Nobuo Katsube.
    • Discovery Research Laboratories III, Minase Research Institute, Ono Pharmaceutical Co, Ltd., 3-1-1 Sakurai Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
    • Anesth. Analg. 2002 Jun 1; 94 (6): 1537-41, table of contents.

    UnlabelledIV prostaglandin E1 improves clinical symptoms in patients with spinal canal stenosis. In the present study, we assessed the effects of OP-1206 alpha-CD, an orally active prostaglandin E1 analog, on walking dysfunction in the rat neuropathic intermittent claudication model. To induce spinal stenosis, two pieces of silicon rubber were placed in the lumbar (L4-6) epidural space in rats. Postsurgical walking function was measured using a treadmill apparatus. Spinal cord blood flow (SCBF) and skin blood flow (SKBF) were measured using a laser-Doppler flowmeter. OP-1206 alpha-CD was administered orally bid for 11 days from postoperative Day 3. In Control nontreated rats, a significant walking dysfunction was observed from Day 1 after the induction of spinal stenosis and persisted for 14 days when compared with the Sham-Operated group. On postoperative Day 15, SCBF revealed a significant reduction in the territory of spinal stenosis, although SKBF was not affected. OP-1206 alpha-CD significantly improved walking dysfunction on postoperative Days 5 (300 microg/kg), 7 (150 and 300 microg/kg), and 14 (150 and 300 microg/kg) when compared with the Vehicle-Treated group. On postoperative Day 15, the decrease in SCBF was significantly (150 and 300 microg/kg) improved by OP-1206 alpha-CD treatment, albeit SKBF remained unaffected. These data show that oral treatment with OP-1206 alpha-CD is effective in improving walking dysfunction induced by spinal canal stenosis, and this therapeutic effect is likely mediated by improved SCBF at the territory of spinal stenosis.ImplicationsIntermittent motor dysfunction is a clinical symptom associated with partial spinal compression. The present study provides evidence that oral treatment with the prostaglandin E1 analog (OP-1206 alpha-CD) is effective in improving motor dysfunction and spinal cord blood flow in rats with spinal compression.

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