limaprost and Spinal-Stenosis

limaprost has been researched along with Spinal-Stenosis* in 15 studies

Reviews

4 review(s) available for limaprost and Spinal-Stenosis

ArticleYear
Lumbar Spinal Stenosis and Potential Management With Prostaglandin E1 Analogs.
    American journal of physical medicine & rehabilitation, 2021, 03-01, Volume: 100, Issue:3

    Lumbar spinal stenosis is one of the most commonly diagnosed spinal disorders worldwide and remains a major cause for surgery in older adults. Lumbar spinal stenosis is clinically defined as a progressive degenerative disorder with low back pain and associated neurogenic intermittent claudication. Conservative and surgical management of lumbar spinal stenosis has been shown to be minimally effective on its symptoms. A treatment option that has not been investigated in the United States is the utilization of prostaglandin E1 analogs, which have been used primarily in Japan for the treatment of lumbar spinal stenosis since the 1980s. The vasodilatory and antiplatelet aggregation effects of prostaglandin E1 presumably improve symptoms of lumbar spinal stenosis by increasing blood flow to the spinal nerve roots. This brief report examines the potential vascular pathology of lumbar spinal stenosis, reviews evidence on the use of prostaglandin E1 analog limaprost in Japan for lumbar spinal stenosis, and briefly discusses misoprostol as a possible alternative in the United States. The studies summarized in this report suggest that prostaglandin E1 analogs may provide benefit as a conservative treatment option for patients with lumbar spinal stenosis. However, higher-quality studies conducted in the United States and comparison with other currently used conservative treatments are required before it can be recommended for routine clinical use.

    Topics: Alprostadil; Humans; Misoprostol; Prostaglandins E, Synthetic; Spinal Stenosis

2021
Prostaglandin E1 Treatment for Lumbar Spinal Canal Stenosis: Review of the Literature.
    Pain practice : the official journal of World Institute of Pain, 2016, Volume: 16, Issue:2

    The important pathophysiologic factor of neurogenic intermittent claudication (NIC) in lumbar spinal canal stenosis (LSCS) has been reported to be the reduction in intraneural blood flow and a state of relative ischemia in nerve tissues. Prostaglandin E1 (PGE1) presumably improves symptoms in patients with LSCS by improving the blood flow in the cauda equina and nerve roots through its vasodilation and antiplatelet aggregation effects. The purpose of the study was to summarize the results of previous studies regarding PGE1 treatment for LSCS and to describe the details of PGE1 treatment to all physicians who take care of patients with LSCS.. Review of the literature.. There are 3 PGE1-related products that have been used clinically for the treatment of LSCS: PGE1, lipo-PGE1, and limaprost (PGE1 derivative). Experimental studies have been performed to verify the efficacy of PGE1 treatment for LSCS. Many studies have reported clinical outcomes of PGE1 treatment in patients with LSCS. Overall, previous studies examining PGE1 treatment for LSCS demonstrate improvement in several clinical outcome measures such as the visual analog scale, Japanese Orthopaedic Association score, and NIC distance, although most of the studies have only short-term follow-up.. Based on the results of previous studies, PGE1 treatment may be an option as a conservative treatment for LSCS. However, future studies with high-quality and long-term follow-up are necessary. Future studies also should include refinement of indications, administration period, as well as comparisons between PGE1 treatment and other conservative treatments such as epidural injection.

    Topics: Adult; Aged; Alprostadil; Female; Humans; Intermittent Claudication; Male; Middle Aged; Spinal Stenosis; Vasodilator Agents

2016
Lumbar spinal stenosis: a brief review of the nonsurgical management.
    Canadian journal of anaesthesia = Journal canadien d'anesthesie, 2010, Volume: 57, Issue:7

    The purpose of this brief narrative review is to summarize the evidence derived from randomized controlled trials pertaining to the nonsurgical treatment of lumbar spinal stenosis (LSS).. The MEDLINE (January 1950 to the fourth week of January 2010) and EMBASE (January 1980 to 2009, week 53) databases, the MESH term "spinal stenosis", and the key words, "vertebral canal stenosis" and "neurogenic claudication", were searched. Results were limited to randomized controlled trials (RCTs) conducted on human subjects, written in English, and published in peer-reviewed journals. Only RCTs pertaining to nonsurgical treatment were considered. Studies comparing conservative and surgical management or different surgical techniques were not included in the review.. The search criteria yielded 13 RCTs. The average enrolment was 54 subjects per study. Blinded assessment and sample size justification were provided in 85% and 39% of RCTs, respectively. The available evidence suggests that parenteral calcitonin, but not intranasal calcitonin, can transiently decrease pain in patients with LSS. In the setting of epidural blocks, local anesthetics can improve pain and function, but the benefits seem short-lived. The available evidence does not support the addition of steroids to local anesthetic agents. Based on the limited evidence, passive physical therapy seems to provide minimal benefits in LSS. The optimal regimen for active physiotherapy remains unknown. Although benefits have been reported with gabapentin, limaprost, methylcobalamin, and epidural adhesiolysis, further trials are required to validate these findings.. Because of their variable quality, published RCTs can provide only limited evidence to formulate recommendations pertaining to the nonsurgical treatment of LSS. In this narrative review, no study was excluded based on factors such as sample size justification, statistical power, blinding, definition of intervention allocation, or clinical outcomes. This aspect may represent a limitation as it may serve to overemphasize evidence derived from "weaker" trials. Further well-designed RCTs are warranted.

    Topics: Administration, Intranasal; Alprostadil; Amines; Analgesics, Non-Narcotic; Anesthetics, Local; Anti-Inflammatory Agents; Calcitonin; Cyclohexanecarboxylic Acids; Epidural Space; Gabapentin; gamma-Aminobutyric Acid; Humans; Injections, Spinal; Pain; Randomized Controlled Trials as Topic; Research Design; Spinal Stenosis; Vitamin B 12

2010
Limaprost.
    Drugs, 2007, Volume: 67, Issue:1

    Limaprost, an alprostadil (prostaglandin E1) analogue, is a vasodilator that increases blood flow and inhibits platelet aggregation. The efficacy of oral limaprost was evaluated in adult Japanese patients in three randomised, double-blind, 6-week trials. One study included patients with thromboangiitis obliterans and two trials included patients with lumbar spinal canal stenosis. Limaprost was generally well tolerated and serious adverse events were uncommon. THROMBOANGIITIS OBLITERANS: In a randomised, double-blind trial in Japanese patients primarily with thromboangiitis obliterans (n=136), there was no significant difference between patients receiving limaprost 30 microg/day and those receiving oral ticlopidine 500 microg/day in the improvement of ischaemic symptoms. LUMBAR SPINAL CANAL STENOSIS: Limaprost 15 microg/day was superior to limaprost 3 microg/day for overall drug usefulness and overall improvement from baseline to study end in a phase III trial in 146 patients with lumbar spinal canal stenosis. Assessment of overall improvement considered various objective symptoms (e.g. muscle strength, walking ability) and subjective symptoms (e.g. pain or numbness in extremities), while overall usefulness also considered safety issues. The efficacy of limaprost 15 microg/day was not significantly different from that of 30 microg/day, but tended to be better than that of 6 microg/day in a phase II trial in patients with lumbar spinal canal stenosis and normal straight leg raise test results. The optimal dosage of limaprost for this indication was therefore deemed to be 15 microg/day.

    Topics: Alprostadil; Animals; Clinical Trials as Topic; Humans; Lumbar Vertebrae; Platelet Aggregation Inhibitors; Spinal Stenosis; Thromboangiitis Obliterans; Vasodilator Agents

2007

Trials

5 trial(s) available for limaprost and Spinal-Stenosis

ArticleYear
Comparative study of the efficacy of limaprost and pregabalin as single agents and in combination for the treatment of lumbar spinal stenosis: a prospective, double-blind, randomized controlled non-inferiority trial.
    The spine journal : official journal of the North American Spine Society, 2016, Volume: 16, Issue:6

    Although the simultaneous management of neuronal ischemia-related pain and compression-demyelination-related neuropathic pain is considered optimal in treating lumbar spinal stenosis (LSS), the effect of combination therapy with pregabalin and limaprost has not been elucidated.. This study aimed to compare the effects of limaprost and pregabalin individually and in combination for the treatment of LSS.. This is a prospective, double-blind, double-dummy, randomized controlled trial.. The sample consists of patients with LSS.. The baseline-adjusted Oswestry Disability Index (ODI) score, visual analog scale (VAS) scores for leg pain, the European Quality of Life-5 dimensions (EQ-5D), and initial claudication distance (ICD).. The present study (ClinicalTrials.gov, number NCT01888536) was a prospective, double-blind, double-dummy, randomized controlled trial designed to determine the efficacy of limaprost in alleviating leg pain, improving disability, and increasing walking distance in persons with degenerative LSS in three different treatment groups: limaprost alone, pregabalin alone, and combined limaprost and pregabalin through 1:1:1 allocation. The primary outcome was the baseline-adjusted ODI score at 8 weeks after treatment. The non-inferior margin of the ODI was set at δ=10 points.. The baseline-adjusted ODI score (primary outcome) at 8 weeks after treatment in the limaprost group was not inferior to those in the pregabalin and limaprost+pregabalin groups. The overall changes of the baseline-adjusted ODI scores, VAS scores for leg pain, the EQ-5D, and ICD during the follow-up assessments over an 8-week period (secondary end point) were not different among the three groups. The baseline-adjusted ODI scores and VAS scores for leg pain decreasedsignificantly over time after treatment in all three groups. The baseline-adjusted EQ-5D score and ICD also increased significantly over time after treatment in all three groups.. The efficacy of limaprost for lumbar spinal stenosis was not inferior compared with that of pregabalin or the combination of limaprost and pregabalin in terms of disability. Therefore, combined treatment with limaprost and pregabalin does not provide additional relief in symptoms in patients with LSS compared with monotherapy with limaprost or pregabalin.

    Topics: Adult; Aged; Alprostadil; Analgesics; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lumbosacral Region; Male; Middle Aged; Pregabalin; Prospective Studies; Quality of Life; Spinal Stenosis

2016
The NMatrix, a new method of presenting statistics, displays the characteristics of medicines with similar effects used in the treatment of lumbar spinal stenosis concisely and clearly, facilitating the selection of appropriate medications.
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2015, Volume: 20, Issue:4

    It is often difficult to compare the characteristics of a medicine with those of others based on common standards, whereas the application of rational standards would be expected to facilitate the comparison of medicines with similar effects. The present study was conducted to clarify the characteristics of individual medicines and to examine whether rational standards allow the most appropriate medicines to be chosen.. Participants diagnosed with lumbar spinal stenosis (LSS) were assessed for QOL and ADL based on the Roland-Morris Disability Questionnaire, JOA score, VAS, and the presence of intermittent claudication (IC). Four medicines--beraprost sodium, ethyl icosapentate (EPA), sarpogrelate hydrochloride, and limaprost alfadex (PGE1)--were prescribed in a random manner. These four medicines were assessed independently in four studies using the same study design and size in each case. Using the NMatrix, the characteristics of the four medicines and the results of mutual comparisons could be displayed concisely and clearly in one matrix based on significance levels. This work involved analyzing pooled data from the four studies.. All four medicines improved IC--one of the characteristic symptoms of LSS--by 12 weeks after administration. PGE1 required more time than the other medicines to affect IC. EPA appeared to almost significantly ameliorate some items at every point, though the evidence was insufficient.. The NMatrix concisely and clearly displays the characteristics of "medicines with similar effects" for the treatment of lumbar spinal stenosis, and can help physicians to choose the optimal medicine based on rational criteria for individual patients, according to their symptoms and progress.

    Topics: Aged; Aged, 80 and over; alpha-Cyclodextrins; Alprostadil; Decision Making; Eicosapentaenoic Acid; Epoprostenol; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Pain Measurement; Platelet Aggregation Inhibitors; Sciatica; Spinal Stenosis; Succinates; Treatment Outcome

2015
Limaprost alfadex and nonsteroidal anti-inflammatory drugs for sciatica due to lumbar spinal stenosis.
    European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2013, Volume: 22, Issue:4

    Limaprost, a prostaglandin E1 analog, has vasodilatory properties and increases blood flow of the nerve root. However, it has not been clarified whether limaprost affects pain sensation associated with radiculopathy due to lumbar spinal stenosis (LSS). The aim of this study was to compare the efficacy of oral limaprost with nonsteroidal anti-inflammatory drugs (NSAIDs) for radiculopathy.. We performed a multicenter prospective randomized trial. Patients with LSS who had radicular-type neurologic intermittent claudication assessed based on a self-reported diagnostic support tool were randomized into three treatment groups. Limaprost, NSAIDs, or limaprost plus NSAIDs were administered orally for 6 weeks. Leg pain, low back pain (LBP) and the associated symptoms were assessed by a numerical rating scale (NRS) both at rest and on movement as well as the Roland-Morris Disability Questionnaire (RDQ) and Short Form (SF)-36.. Sixty-one patients were enrolled in the study. Each treatment finally reduced radicular pain, and the improvement was prominent in a combination treatment. There were no significant differences in radicular pain among three groups at final follow-up. LBP was not influenced by limaprost, and a significant reduction of LBP and RDQ was confirmed in a combination treatment compared with limaprost. Physical function of the SF-36 subscales after a combination treatment showed a marked alleviation compared with NSAIDs.. These obtained findings suggest that the effects of limaprost seem to be limited to radicular pain, not for LBP. Overall, a combination treatment might be more effective in the management of radiculopathy induced by LSS than monotherapy with either agent.

    Topics: Administration, Oral; Aged; alpha-Cyclodextrins; Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Disability Evaluation; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Sciatica; Spinal Stenosis; Surveys and Questionnaires; Treatment Outcome

2013
The efficacy of prostaglandin E1 derivative in patients with lumbar spinal stenosis.
    Spine, 2009, Jan-15, Volume: 34, Issue:2

    Randomized controlled trial.. To examine the effect of limaprost, an oral prostaglandin (PG) E1 derivative, on health-related quality of life (HRQOL) in patients with symptomatic lumbar spinal stenosis (LSS), compared to etodolac, a NSAID.. Limaprost, an oral PGE1 derivative, was developed in Japan to treat numerous ischemic symptoms of thromboangiitis obliterans (TAO) and LSS. Previous studies have demonstrated the effectiveness of limaprost in the symptoms in patients with LSS. However, the evidence for effect on patient-reported outcomes, such as patient's HRQOL or satisfaction, is limited.. This study was conducted at 4 study sites in Japan. Briefly, inclusion criteria were: age between 50 and 85 years; presence of both neurogenic intermittent claudication (NIC) and cauda equina symptoms (at least presence of bilateral numbness in the lower limbs); and MRI-confirmed central stenosis with acquired degenerative LSS. Limaprost (15 microg/d) or etodolac (400 mg/d) was administered for 8 weeks. The primary outcome was Short Form (SF)-36, and the secondary outcomes were the verbal rating scale of low back pain and leg numbness, walking distance, subjective improvement, and satisfaction.. A total of 79 participants were randomized (limaprost:etodolac = 39:40). Thirteen participants withdrew from the study (limaprost:etodolac = 5:8) and 66 completed the study (limaprost:etodolac = 34:32). Comparisons showed that limaprost resulted in significantly greater improvements in the SF-36 subscales of physical functioning, role physical, bodily pain, vitality, and mental health. Limaprost was also significantly better than etodolac for leg numbness, NIC distance, and subjective improvement and satisfaction. In the subgroup analysis stratified by symptom severity, limaprost seemed more effective for milder symptoms. No serious adverse effects were reported in either treatment group.. In this study, limaprost was found to be efficacious on most outcome measures, such as HRQOL, symptoms and subjective satisfaction, in LSS patents with cauda equina symptoms.

    Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Back Pain; Etodolac; Female; Gait Disorders, Neurologic; Humans; Hypesthesia; Male; Middle Aged; Pain Measurement; Patient Satisfaction; Polyradiculopathy; Spinal Stenosis; Treatment Outcome

2009
Limaprost alfadex improves myelopathy symptoms in patients with cervical spinal canal stenosis.
    Spine, 2009, Mar-15, Volume: 34, Issue:6

    Myelopathy symptoms were prospectively studied in patients with cervical spinal canal stenosis (CSCS), using objective grading systems and stabilometry, to examine the effect of administration of prostaglandin E1 derivative limaprost alfadex (limaprost).. Myelopathy scores/grades and stabilometry parameters were evaluated before, and 1 and 3 months after starting the limaprost treatment.. Limaprost is a potent vasodilator and antiplatelet agent and has been used to treat the symptoms of lumbar spinal canal stenosis. The action presumably involves increased blood flow in the compressed cauda equina. Limaprost can also increase blood flow in the compressed spinal cord, but effects on myelopathy symptoms in patients with CSCS have not been established.. This study examined 21 patients with mild spondylotic CSCS based on neurologic findings and compression of the cervical spinal cord on magnetic resonance imaging. Japanese Orthopedic Association score, grip and release test, and finger escape sign were measured, and stabilometry was performed by independent examiners, before, and 1 and 3 months after starting the oral limaprost treatment.. Most patients experienced amelioration of the symptoms at 1 month after starting the treatment. Mean Japanese Orthopedic Association score and grip and release count were significantly improved and finger escape sign grade was higher in some patients. Stabilometry area with eyes closed and Romberg rate were also significantly improved. These improvements were maintained at 3 months.. The efficacy of oral limaprost administration for patients with CSCS was confirmed by objective scoring and quantitative data.

    Topics: Administration, Oral; Aged; Aged, 80 and over; Alprostadil; Cervical Vertebrae; Dizziness; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Motor Skills; Platelet Aggregation Inhibitors; Postural Balance; Prospective Studies; Spinal Stenosis; Spondylosis; Treatment Outcome; Vasodilator Agents

2009

Other Studies

6 other study(ies) available for limaprost and Spinal-Stenosis

ArticleYear
Limaprost or Pregabalin: Preoperative and Postoperative Medication for Pain due to Lumbar Spinal Stenosis.
    Pain practice : the official journal of World Institute of Pain, 2018, Volume: 18, Issue:5

    We aimed to evaluate the incidence of (and risk factors for) postoperative pregabalin and/or limaprost to treat persistent numbness and/or pain of the lower extremities after lumbar spinal stenosis (LSS) surgery.. Medical records of 329 patients (168 men, 161 women; average age 70 years) were retrospectively reviewed for data on the duration of LSS diagnosis; LSS disease; preoperative medication (limaprost, pregabalin, or combined limaprost/pregabalin; duration); symptoms; preoperative/postoperative intermittent claudication (IC); operation type; and postoperative medication and period.. Limaprost, pregabalin, and combined limaprost/pregabalin were prescribed preoperatively for 43%, 7%, and 5% of patients, respectively. At an average of 21 months postoperatively, limaprost, pregabalin, and combined therapy were prescribed in 11%, 8%, 4% of patients, respectively. Medication requirement was significantly lower postoperatively than preoperatively (P < 0.0001). Significant risk factors for required postoperative medication were required preoperative medication (odds ratio [OR] 3.088, 95% confidence interval [CI] 1.679 to 5.681]; postoperative period (OR 1.063, 95% CI 1.031 to 1.096); and postoperative IC (OR 3.868, 95% CI 1.481 to 10.103). A negative impact from postoperative medication was seen in patients who had undergone decompression surgery (OR 0.589, 95% CI 0.377 to 0.918).. Overall, 23% of LSS patients required medication for pain and/or numbness at 21 months postoperatively. Significant factors portending required postoperative medication were preoperative medication, longer postoperative period, and postoperative IC. A negative influence from postoperative medication was seen in patients who had undergone decompression surgery without fusion.

    Topics: Aged; Alprostadil; Decompression, Surgical; Female; Humans; Hypesthesia; Lumbar Vertebrae; Male; Middle Aged; Pain; Postoperative Period; Pregabalin; Retrospective Studies; Spinal Stenosis

2018
Predicting Analgesic Use after Spinal Surgery.
    Pain practice : the official journal of World Institute of Pain, 2018, Volume: 18, Issue:6

    Topics: Alprostadil; Analgesics; Humans; Pain; Pregabalin; Spinal Stenosis

2018
The effect of a prostaglandin E1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis.
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2013, Volume: 18, Issue:2

    Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D).. QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0-100).. Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5-15, 15-30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group.. According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.

    Topics: Activities of Daily Living; Aged; Alprostadil; Chi-Square Distribution; Cyclooxygenase 2 Inhibitors; Disability Evaluation; Etodolac; Female; Humans; Intermittent Claudication; Low Back Pain; Lumbar Vertebrae; Male; Pain Measurement; Quality of Life; Spinal Stenosis; Statistics, Nonparametric; Treatment Outcome; Vasodilator Agents; Walking

2013
Activation of extracellular signal-regulated protein kinase in dorsal horn neurons in the rat neuropathic intermittent claudication model.
    Pain, 2004, Volume: 109, Issue:1-2

    Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates several cellular responses to mitogenic and differentiation signals, and activation of ERK in dorsal horn neurons by noxious stimulation is known to contribute to pain hypersensitivity. In order to elucidate the pathophysiological mechanisms of the cauda equina syndrome, secondary to spinal canal stenosis, we evaluated walking dysfunction triggered by forced exercise and activation of ERK in the dorsal horn using a rat model of neuropathic intermittent claudication. Rats in the lumbar canal stenosis (LCS) group showed a shorter running distance from 1 to 14 days after surgery. Two minutes after running on the treadmill apparatus, phosphorylation of ERK was induced in neurons in the superficial laminae in the LCS group but not in the sham group, whereas there was no change in the deeper laminae. Intrathecal administration of the MAPK kinase inhibitor, U0126, 30 min before running, clearly increased the running distance, whereas there was no significant change in the vehicle control group 3 days after surgery. In addition, a prostaglandin E1 analog, OP-1206 alpha-CD, administered orally, improved the walking dysfunction, and further, inhibited activation of ERK following running 7 days after surgery. These findings suggest that intermittent claudication triggered by forced walking might affect the phosphorylation of ERK in the superficial laminae, possibly via transient (partial) ischemia of the spinal cord. ERK activation in the dorsal horn neurons may be involved in the transient pain in the neuropathic intermittent claudication model.

    Topics: Alprostadil; Analysis of Variance; Animals; Butadienes; Disease Models, Animal; Enzyme Inhibitors; Immunohistochemistry; Intermittent Claudication; Male; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Nitriles; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Spinal Stenosis; Walking

2004
Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.
    Prostaglandins, leukotrienes, and essential fatty acids, 2003, Volume: 69, Issue:4

    An orally active prostaglandin E1 analogue, OP-1206 alpha-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 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-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 alpha-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 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-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.

    Topics: Administration, Oral; alpha-Cyclodextrins; Alprostadil; Animals; Cyclodextrins; Disease Models, Animal; Drug Therapy, Combination; Intermittent Claudication; Male; Phenylpropionates; Prostaglandins E, Synthetic; Rats; Rats, Wistar; Regional Blood Flow; Spinal Cord; Spinal Stenosis; Walking

2003
The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model.
    Anesthesia and analgesia, 2002, Volume: 94, Issue:6

    IV 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.. Intermittent 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.

    Topics: Alprostadil; Animals; Intermittent Claudication; Male; Platelet Aggregation Inhibitors; Prostaglandins E, Synthetic; Rats; Rats, Wistar; Regional Blood Flow; Skin; Spinal Cord; Spinal Stenosis; Vasodilator Agents; Walking

2002