$502 Friday, November 11, 2005 Poster Abstracts

Sharma, U 1, Young, j1, LaMoream% L ~, Emir, B 2, Murphy, TK 2, Sant, M 3, Siffert, j.2. 1pfizer Global Research and Development, Pfizer Inc, Ann Arbor, USA," 2Pfizer Global Pharmaceuticals, Pfizer Inc, New York, USA; 3Pfizer Australia, Pfizer Global Pharmaceuticals, Sydney, Australia

Background: The overall analgesic effect of pregabalin as treatment for neuropathic pain (NeP) associated with diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN) was investigated using data from a large patient cohort formed by combining 10 clinical trials. Method: Pregabalin's ability to reduce NeP was assessed in 10 double- blind, placebo-controlled trials involving 2207 patients (1796 received placebo; 406, 457, and 548 received pregabalin 150, 300, and 600 mg/day). The primary efficacy measure was study-end mean pain score derived from patient-recorded daily-pain diaries (11-point scale; 0 -- no pain; 10 -- worst possible pain). Treatment efficacy was also assessed by measuring the proportion of patients who experienced pain reductions >30% and >50% by study-end. Results: Pregabalin-treated patients consistently reported significantly greater pain reductions than those on placebo. On average, patients receiving pregabalin 150, 300, and 600 mg/day reported pain score reductions of 11.8, 2.2, and 2.6 vs 1.2 by placebo patients (P < 0.0001). Pain reductions were positively correlated with dose. 40%, 51%, and 62% of patients on pregabalin 150, 300, and 600 mg/ day reported pain reductions _>30%, while only 30% of placebo patients reported comparable reductions. Similarly, 26%, 34%, and 47% ofpregabalin patients reported reductions _>50% vs only 18% of placebo patients. Treatment-emergent adverse events (AEs) were gen- erally mild/moderate (dizziness and somnolence were the most com- mon). AEs led to withdrawals in 11% ofpregabalin patients and 4% of placebo patients, demonstrating that pregabalin is well tolerated. Conclusion: Treatment with pregabalin yielded significant pain reductions, with as many as 62% of patients reporting clinically meaningful responses (>30%).

1581 Serum level of Serotonine and Substantia P after treatment of Bohllinum Toxin A injections in different dilution

Szczepanska-Szerej, A ~, Wojczal, j1, Kurzepa, j1, Stelmasiak, Z 1. ZDepartment of Neurology, Medical University in Lublin, Poland

Background: Studies of botulinum toxin A (BTXA) for the treatment of painful disorders have led to the understanding of additional mechanisms of action beyond the inhibiting of acetylocholine release. It is known that higher volume resulted in greater diffusion of BTXA. The purpose of tiffs study was to evaluate the effects of BTXA dilution volmne on serum serotonine and substantia P level. Methods: The groups of patients with torticolfis (in -- 16) an fibromyalgia (in - 15) were compared. Patients with torticollis received to the neck muscles 1 to 2 vials of BTXA diluted 1 ml of isotonic. solution per vial. Patients with fibromyalgia received 1 via I of BTX diluted in 10 ml (1 ml to each of 10 tender points). Serums were collected before and 4 weeks after treatment. These results were compared with the results of agematched, free of pain control group (in - 12). Statistics were performed using Mann-Wlfftney U and Wilcoxon's tests. Results: Serum levels of serotonine and substantia P did not differ between patients with torticollis and fibromyalgia before treatment and were similar to the control group. After 4 weeks serum levels of serotonine and substantia P in patients receiving BTXA in small volume did not change statistically. Patients receiving BTX in larger volume has statistically significant higher serum level of serotonine (p < 0,05). Serum level of substantia P remained similar as at the control group and before treatment. Conclusion: The findings indicate that BTXA diluted in higher volume can change serotonine level. It could explain BTXA pain relief mechanism.

1582 Pilot study using Botulinum Toxin a pre-trealment of Lumbar Spine Muscles for relieving post-operative pain

Cannard, KR 1'2, Tsao, 3W 1'2"3, Labutta RJ 1"2, Riechers, RG 1"2, Moqnin RR 1'2, Rosner M K 1'2, Kuklo TR 2, Spencer, N A 1'2, Ling, GSF l'a.~. 1Defense Spinal Cord and Column Infi~ry Program, Washington, DC, USA; ~tValter Reed Army Medical Center, Washington, DC, USA; 3Uniformed Services University of the Health Sciences, Bethesda, MD, USA

Background: Post-operative paraspinal muscle spasm and pain commonly affect the duration and severity of disability and suffering following lumbar surgery. Botulinum toxin A (BotA) has been demon- strated to reduce chronic, low back pain due to muscle strain. We sought to investigate its putative role in relieving pain and enhancing recovery following lumbar disk surgery. Method: Fifteen subjects (14 M, 1 F) were enrolled in a prospective, double-blind, placebo-controlled trial of BotA. Subjects were injected 4-14 days (mean, 12 days) prior to surgery with 400 units BotA (150 units at each of 8 sites divided bilaterally at 4 lumbar spine levels). Subjects rated their pain and disability on the visual analog scale (VAS) and Oswestry Low Back Pain Questionnaire (OLBPQ) at enrollment and 3 days, 4 weeks, and 8 weeks following surgery. Results: The VAS scores of 7 BotA subjects was 6.6 ± 3.0 cm (mean ± SD) initially, declining to 6.3 ± 2.6 cm at 3 days, 4.2 ± 1.5 can at4 weeks, and 3.8 ± 2.8 cm at 8 weeks after surgery. The 8 placebo-treated subjects had similar declines from 6.5 ± 1.8 can to 5.6 ± 2.7 cm to 3.6 ± 2.1 can to 2.7 ± 1.8 cm, respectively (]p - 0.52). The Oswestry Disability Index (calculated from the OLBPQ) also was not different between BotA- treated (48 ± 20 initially, 66 ± 10 at 3 days, 47 ± 12 at 4 weeks, 35 ± 20 at 8 weeks post-surgery) and placebo-treated (38 ± 8, 66 ± 12, 35 ± 14, 24 ± 3, respectively) groups at any time point (p - 0.83). Conclusion: In tiffs on-going clinical trial, preliminary results suggest that BotA does not improve post-operative pain or speed recovery following lmnbar surgery.

1583 Verapanfil enhances tile modulatory efl~cts of stress and Dexamethasone on acute pain in mice

Vafaei, A l, Taherian, A ~. 1Physiology research center, Semnan University of Medical Sciences, Semnan, Iron

Previous study indicated that acute stress and glucocorticoids have modulatory effects on acute pain. The aim of present study was determine of interaction between of stress and glucocorticoids with activation of voltage dependent Ca ++ channel on modulation of acute pain in mice. In this experimental study we used of male albino mice (125-30 gr, n -- 120 in 12 groups) were used for this experiment. Tail flick and Hot plate were used for evaluation of analgesic effect of the drug. We used of subcutaneous injection of velffcle or dexamethasone (DEX) or 10 min restricted stress 30 min before of the observation period. Also we used of Verapamil (15 and 10 mg, IP) as a voltage Ca ++ channel blocker 10 rain before of DEX and stress. Also at the end, all animal was killed and blood corticosterone was measured.

Results indicated that DEX and stress have analgesia effects in compare with control group and Verapamil can be increase sig- nificantly of tiffs effects (P < 0.01). Finding above provide further evidence for an important role of stress and glucocorticoids on modulation of pain and probably interaction with these effects and activation of voltage dependent Ca ++ channel.

1584 Differences and similarities in the Phaxmacoldnetic properties of P~egabalin and Gabapentin

Wesche, D 1, Fukui, A 2, Bockbrader, H 1. ZPfizer Global Research and Development, Pfizer Inc, Ann Arbor, USA," 2Pfizer Australia, Pfizer Global Pharmaceuticals, Sydney, Australia