$500 Friday, November 11, 2005 Poster Abstracts

Methods: Complex examinations were performed in 597 patients. Groups of patients were formed on pathogenic situation's dynamics new concept and 7 types of ID dantage definition. Ill patients with prolapses of ID (1 ~t group - 144 cases) we find out complete and partial prolapses. In patients with protrusion of ID (2 ~i group - 144 cases) we define sequestrated and elastic types. In patients with instability of spine (3 "a group - 309 cases) we determine preceding pathology of ID - prolapses (23,5%), protrusions (11,4%), or rupture of fibrotic ring (116,9%). Results: In 21 patients of 1 ~t groups with CO we can give indication for the decompression of roots by anterior approach to spine. In 1 ~t group of patients with LO we used the posterior approach to spine for decompression of nerve roots (1143 cases). In 454 patients of 2 n~i and 3 "a groups the puncture's operations (dereceprion or medical glue stabilization of ID) were made. Its was effective in 55,3"/0 cases. In other cases the discectomy and interbody fusion by anterior approach to hinlbar spine was done. Complete recovery and improventent was observed in 86,7?,'0 of patients, disability - in 8,7?,'0 cases. Recurrence of the CPS was in 4,6?,'0 cases. Conclusion: Formation of clinical groups of patients depending on ID damage allowed choosing effective pathogenic treatment

I573 Role of Acetyl l l -Keto beta Boswellic Add, a Lipooxygenase ildlibitor in the Antinociceptive effect of NSAID's

Kumar, A l, Bishnni, M ~, Patti, CS l, Kulkarni, SK 1. 1Pharmacology Division, University Institute of Pharmaceutical Sciences, Chandigarh, India

Objectives: The present study was aimed to assess the combined effects of cyclooxygenase and 5-1ipoxygenase (COX/5-LOX) inhibitors in different animal models of nociception. Naproxen, nimesulide and rofecoxib are well-established antinociceprive agents acting via COX inhibition. AKBA (Acetyl-keto-beta-boswellic acid) is a 5-LOX inlfibitor. AKBA (150-200 mg/kg) produced a dose dependent and significant antinociceptive effect in different animal models of nociception. Method: in the present study, tail flick, hot plate, acetic acid induced writhing and tail immersion tests were done. Results were expressed as maximum possible effect. Results: Based on the earlier reports from our laboratory, sub effective doses of all the three COX Inhibitors were selected and they were administered (naproxen, 5 mg/kg, nimesulide, 1 mg/kg and rofecoxib, 1 mg/kg) with AKBA (100 mg/kg). This produced a more anti- nociceptive effect as compared to the per se effect observed in all the three models of nociception. However the effect of combination of nimesulide with AKBA was more pronounced as compared to naproxen and rofecoxib and their combination with AKBA. Conclusion: The present finding provided an evidence for the potentiation of antinociceptive effect of NSAID's with AKBA. Such a combination may help to reduce the therapeutic doses of conven- tional NSAID's and also reduce side effects (gastric, cardiac and renal) that are popularly associated with the NSAID's.

1874 High-affinity binding of Pregabalin at Alpha-2-Delta (:t2-~ } mbunits of voltage-gated calcium channel - contribution to pharmacological action

Li, Z ~, Donevan, S ~, Taylor, C ~, Oflbrd, ja, Su, T a, Vartanian, M a, Bian, F 1, Wustrow, D 1, Schwarz, j1, Thorpe, A 1. 2CNS Discovery, Pfizer Global Research and Development, Ann Arbor, United States of America

Background: Pregabalin shows analgesic-like, anticonvulsant, and amxiolytic-like actions in animal models and positive results in clinical studies of neuropatlfic pain, partial seizures, and anxiety disorders. We investigated the role of alpha-2-delta ( ~ ~) binding on the pharmacology of pregabalin in rodent models.

Method: Receptor-binding studies and behavioral analysis using DBA/2 anticonvulsant test were used. Results: Pregabalin binds with lfigh affinity to recombinant c ~ 6 type- 1 and type-2 proteins (KD -- 6 and 7 nM, respectively). These values are similar to those with membranes isolated from native mouse, rat, porcine or human brain. Pregabalin did not alter radioligand binding at 38 other commonly studied drug sites, indicating that ct2-6 proteins are the primary binding sites for pregabalin. We generated a c~2-8 type-1 mouse strain with a single amino acid mutation from arginine 217 to alanine (R217A). The mutation reduced binding affinity for radioligand in vitro by 20-fold. R217A mice had reduced binding of radioligand to neocortex (KD increased from 10 to 238 aM), hippocampus, amygdala and dorsal spinal cord, but relatively un- changed binding in cerebellum. R217A mice had reduced potency of pregabalin for anticonvulsant action. Experiments with compounds structurally related to pregabalin showed a correlation between affinity for binding to c~ 2 6 and in vivo activityin analgesia and anticonvulsant models. Conclusion: These results suggest that high affinity binding to the aa-3 protein is required for the pharmacologic action of pregabalin. Pregabalin and gabapentin define a novel class of CNS drugs, binding at c~ 2 6 protein. Pfizer Funded.

1575 Lumbar Zygapophyseal Joint Injections in Patients with Chronic Lower Back Pain

Juei-Jueng Lin 1, Chunhsi Stfih 2, Gin-Yau Lin 3. 1Department of Neurology, Chu-Shang Show-Chwan Hospital, Nantou, Taiwan; 2Department of Radiology, Chu-Shang Show-Chwan Hospital, Nantou, Taiwan; 3Department of Surgery, Chu-Shang Show-Chwan Hospital, Nantou, Taiwan

Background: This study was designed to assess the diagnostic value and clinical benefits of lmnbar zygapophyseal joint injections in patients with chronic lower back pain. Methods: Two hundred and seventy-seven patients (136 males and 141 females, aged 15-82 years) with chronic lower back pain were enrolled in the trial and met the following criteria: pain for more than 1 year; no root signs; and no history of back surgery. Under fluoroscope, a 0.8-1.5 niL mixture of lidocaine, betanlethasone dipropionate and iopamidol (1:1:0.5) was injected into each joint after intra-articular localization of the needle tip was confirmed. A questionnaire with a pain scale was administered immediately or the day after injection, and then after 1, 3, 6 and 12 weeks. Partial arthrograms were reviewed by a radiologist. Results: Four hundred and forty-nine joint injections were perforated in 277 patients (L3-4, n - 76; L4-5, n - 272; L5 S1, n -- 101). Bilateral injections were performed in 117 patients (42.20'0). The study group comprised 204 patients (73.6%) with an excellent or good response, whereas the control group comprised the remaining 73 patients (26.4"/0). The rates of good response in the study group were 72.1"/o (147/204) after 3 weeks, 40.7% (83/204) after 6 weeks, and 31.4"/0 (164/ 204) after 12 weeks. Partial arthrograms revealed 25 patients (19.0"/o) with synovial cysts (L3-4, n -- 3; L4-5, n -- 14; L5-S 1, n -- 8); 23 of these patients (92.0?,'0) had a good response to the injections. Five of the six patients with spondylolysis (183.3%), having abnormal comnmnication between the injected and contiguous joint, had a good response to the injections. The abovementioned, abnormal partial-arthrogram findings correlated significantly with the rate of good response to the injections. Although three patients had contrast medium extravasated into the epidural space during injection, none of the 277 patients had deteriorating lower back pain after the injections. Conclusions; Lumbar zygapophyseal joint injections, as a useful diagnostic tool for facet joint syndrome, could also have useful palliative effects in the management of chronic lower back pain.