NIC is a characteristic symptom among patients with lumbar spinal canal stenosis. It is aggravated by walking and leads to reductions in walking distance. Reduced intraneural blood flow is one cause of NIC [
3,
7]. Administration of PGE
1 derivate and calcitonin, which are thought to improve blood flow, has been reported to improve walking distance of patients with NIC [
1,
20]. Intravenous administration of PGE
1 increases nerve root blood flow velocity after lumbar diskectomy in spinal stenosis patients [
21]. Experimental studies of PGE
1 treatments have also been reported. Compression of cauda equina reduced blood flow in spinal nerve roots [
4,
5] and PGE
1 increased blood flow and prevented the reduction in nerve conduction velocity in acute cauda equina compression [
17]. In addition, intravenous injection of PGE
1 derivative increased blood flow in chronic cauda equina compression [
9]. In this study, the diameter of the arteries, but not the veins, increased after administration of PGE
1 derivative under cauda equina compression. In addition, blood flow in the arteries increased after administration of PGE
1 derivative. These results suggest that the PGE
1 derivative has a vasodilatory effect and increases blood flow in arteries. No changes in blood pressure were observed following administration of the PGE
1 derivate, and blood flow velocity was maintained during vasodilation. These findings indicate that the vasodilatory effect of the PGE
1 derivate on arteries enables increased blood flow without inducing blood stasis. In veins, the PGE
1 derivate did not cause vasodilation or increases in blood flow. In clinical practice, PGE
1 derivative will be given orally or as an intravenous bolus. In the present study, PGE
1 derivative was administrated orally and the duration of the vasodilatory effect was 90 minutes. In this experimental setting, it was difficult to investigate the duration of the effect of the PGE
1 derivative after oral administration; however, because the half-life of this drug is 7 hours through the stomach in a rat and the increased of vasodilatation was approximately 9% at 90 minutes, we can assume that the duration of vasodilatation was more than 90 minutes in this model.
The actions of PGE
1 are mediated primarily by the IP receptor, and include a vasodilatory effect as well as a platelet aggregation inhibition effect mediated by PGI
2. The IP receptor is expressed in smooth muscle cells of various organs such as the aorta, coronary arteries, pulmonary arteries, and cerebral arteries, whereas no expression is found in veins [
22]. However, PGE
1 is known to dilate both arterioles and venules [
6]. In addition, cyclic GMP is associated with smooth muscle relaxation, which is a different mechanism of vasodilation mediated by the IP receptor [
23]. PGE
1 also inhibits aggregation of platelets [
24] and increases peripheral venous pressure [
25] in experimental studies. In a clinical study, PGE
1 administration at a low infusion rate of 0.02 μg/kg/min increased cardiac output without altering mean arterial blood pressure and blood volume [
26]. In a canine model, from 3.8 to 5.6 ng/kg/min PGE
1 intravenously did not influence systemic mean arterial pressure. Therefore, PGE
1 may change arterial blood flow in the nerve roots due to both primary and secondary effects.
In this study, the arteries reacted to the administration of PGE
1 derivative whereas the veins did not. However, one limitation of this study was that the changes in the diameter and blood flow in arteries and veins were observed for only 90 minutes. Another limitation of this study was that walking capacity could not be investigated before and after administration of the PGE
1 derivative. However, in a rat model, orally administered PGE
1 improved walking dysfunction and blood flow [
16]. The increase of nerve root blood flow may improve function of the nerve root and lead to an improvement in walking capacity. According to the previous clinical reports, PGE
1 derivative may be a potential therapeutic agent for lumbar spinal stenosis with NIC.