10th World Congress on Pain, List of topics

EFFECT SIZE OF ANALGESIC AGENTS ON KEY OUTCOME VARIABLES IN OSTEOARTHRITIS
P. Peloso, N. Babul, Department of Internal Medicine, University of Iowa Hospital and Clinics, Iowa City, IA , Clinical Drug Development, TheraQuest Biosciences, East Norriton, PA

Aim of Investigation: A wide variety of pharmacologic agents are used singly or in combination to treat the symptoms of osteoarthritis, including NSAIDs, COX-2 inhibitors and opioids. Although information on minimum clinically important and perceptible differences in osteoarthritis is available, selection of therapy is at least partly based on clinician perceptions about relative safety and efficacy. The purpose of this study was to compare the true effect size following therapeutic doses of agents commonly used to treat OA.

Methods: A literature search of Medline was conducted to obtain data on randomized, double blind, placebo controlled trials of analgesics in osteoarthritis. To minimize publication bias, data submitted to the FDA were also obtained under the Freedom of Information. Data on overall pain intensity, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores for index joint pain, stiffness and physical function subscale scores and patient global were collected. The True Effect Size was expressed as the response on drug, less the response on placebo ([ Drug/Baseline Drug] [ Placebo/Baseline Placebo] x 100%).

Results: For index joint pain intensity, the True Effect Size range for NSAIDS, COX-2 inhibitors and opioids were 8-18%, 9-23% and 23-39%, respectively.

Conclusions: There was considerable intra-drug and inter-drug variability in response. Interpretation of data was hampered by differences in study design (flare vs. washout; rescue; primary vs. add-on therapy), statistical approaches (choice of primary efficacy variable and endpoint; intent-to-treat vs. evaluable population; imputation techniques) and dose of study drug.

EFFECTS OF INTRAVENOUS KETOROLAC AND FENTANYL ON ANALGESIA AND SIDE EFFECTS DURING EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY
C. Cherng, Anesthesiology Tri-Service General Hospital, National Defense Medical Center., Taipei, Taiwan

AIM OF INVESTIGATION: This study was to compared the effects of intravenous ketorolac and fentanyl on analgesia and side effects during extracorporeal shock wave lithotripsy (ESWL).

METHODS: Sixty patients were divided into two groups randomly, group K (n=30) received 60 mg ketorolac (i.v.) 30 min before ESWL and group F (n=30) received 100 microgram fentanyl (i.v.) 3 min before ESWL. All patients received 2.5 mg midazolam 3 min before ESWL for intraoperative sedation. The pain intensity was evaluated by a numeric rating scale (NRS). A supplemental analgesia was administered by 25 microgram fentanyl when inadequate analgesia occurred (NRS>3). Oxygen supplement with face mask was given when SpO2 below 94%. Side effects (nausea, vomiting, dizziness) and the discharge times from PAR were recorded. The discharge criterion was defined as there was no any discomfort even when standing up.

RESULTS: There was no difference between two groups in demographic data, number of shock waves, duration of ESWL procedure, and fentanyl supplement. The incidence of oxygen supplement was lower in ketorolac group (1/30) than that of fentanyl group (20/30), p<0.01. The frequency of dizziness was lower in ketorolac group (1/30) than that of fentanyl group (25/30), p<0.01. Three patients in fentanyl group complained of nausea, but none in ketorolac group. The discharge time from PAR was significantly shorter in ketorolac group (13.78.4 min) than that of fentanyl group (49.514.6 min), p<0.01.

CONCLUSIONS: Both intravenous ketorolac and fentanyl could provide good analgesia for ESWL. However, ketorolac demonstrated less side effects and shorter discharge time from PAR.

EFFECTS OF A SINGLE DOSE OF ACETYLSALICYLIC ACID ON SORE THROAT PAIN, AND OTHER PAIN SYMPTOMS, ASSOCIATED WITH ACUTE UPPER RESPIRATORY TRACT INFECTION
R. Eccles, L. Nyman, I. Loose, Common Cold Centre, Cardiff University, Cardiff, United Kingdom , Quintiles AB, Quintiles, Uppsala, Sweden , Consumer Care, Bayer AG, Leverkusen, Germany

AIM OF INVESTIGATION: Acetylsalicylic acid (ASA) has a long tradition in the treatment of symptoms of acute upper respiratory tract infection (URTI) yet modern clinical trials data is sparse for this indication. This study investigates the efficacy and safety of a single dose of 800mg ASA on treatment of pain symptoms associated with URTI.

METHODS: A double blind, placebo controlled, parallel group design. Patients with sore throat pain associated with URTI were recruited at two centres. They were treated with either two effervescent tablets of ASA 400mg in water or matched placebo tablets. Primary study objective was sum of sore throat pain intensity differences (SPID) for 0-2hours. Pain and pain relief scores were made during a two hour in patient phase and continued for secondary objectives during a four hours home phase.

RESULTS: 272 of 279 patients fulfilled all protocol requirements. ASA was found to be superior to placebo for SPID 0-2hours (p < 0.0001). It was also superior to placebo in the reduction in sore throat pain intensity, and relief of sore throat pain for 2,4 and 6 hours (p < 0.002); reduction in intensity of pain associated with headache (p < 0.002), and muscle aches and pains (p < 0.02) at 2 hours. No safety problems were encountered.

CONCLUSIONS: Treatment with ASA has been shown to provide relief from sore throat pain, headache, and muscle aches and pains associated with URTI.

ACKNOWLEDGEMENTS: This study was sponsored by Bayer AG, Germany.

SAFETY AND EFFICACY OF REPEATED DOSES OF DEXKETOPROFEN TROMETAMOL I.V. IN THE MANAGEMENT OF POST-ORTHOPAEDIC SURGICAL PAIN
H. Zippel, R. Artigas, M. Bertolotti, A. Capriati, M. Ballarin, Abteilung Orthopdie, Humboldt, Universitt Charit, Berlin, Germany , Clinical Research, Menarini Ricerche S.p.A., Florence, Italy

Aim of investigation: To evaluate the safety and analgesic efficacy of repeated I.V. administrations of dexketoprofen trometamol (DKP.TRIS) in patients following major orthopaedic surgery.

Methods: A total of 252 pts, presenting with moderate-severe pain within 12 h post recovery from general anaesthesia after hip or knee replacement surgery, were randomised to receive DKP.TRIS 50 mg or to ketoprofen (KP) 100 mg (100 ml infusion over 30 min every 8 h for two days). Rescue medication included paracetamol or morphine; PCA was not allowed. The primary end-point for efficacy was pain intensity reduction measured by SAPID_0-8h. Safety was evaluated by monitoring lab parameters and AEs.

Results: The study population encompassed 60% M; the mean age was 60 y; 70% undergoing hip replacement. Baseline pain intensity was scored as severe (mean VAS=75 mm). A marked pain relief was obtained following the first dose of both DKP.TRIS and KP (SAPID_0-8h=311 and 326 mm.h); pain remained controlled during the study period (mean PID after 8h from start of each dose administration=43 and 47 mm). As expected, rescue medication was taken by the majority of pts, with no overt difference between DKP.TRIS and KP (81% vs 87%). A good safety profile was observed with 16% and 21% pts reporting ADRs in DKP.TRIS and KP groups, respectively. The rate of AEs, including bleeding, did not differ in pts treated with heparin or low molecular weigh heparin for the prophyilaxis of thrombo-embolic complication.

Conclusion: DKP-TRIS given as 50 mg I.V. t.i.d. was safe and efficient in the management of severe post-orthopaedic pain.

Acknowledgments: Supported by grants from Menarini Ricerche S.p.A.

DEXKETOPROFEN TROMETAMOL VERSUS TRAMADOL IN THE RELIEF OF PAIN FOLLOWING MAJOR ORTHOPAEDIC SURGERY
S. Peat, I. Paredes^, A. Capriati, Dept. of Anaesthetics, King's College Hospital, London, United Kingdom , Clinical Research, Menarini Ricerche S.p.A., Florence, Italy

Aim of investigation: To evaluate the efficacy and safety of dexketoprofen trometamol (DKT.TRIS) versus tramadol (T) in the control of pain following major orthopaedic surgery.

Methods: 215 M and F patients (age 18-75) undergoing primary hip or knee replacement were randomised to receive 50 mg DKP.TRIS (over 30 min), 100 mg T (bolus) or placebo (P) given I.V. according to a double blind, double-dummy design. All pts also received I.V. morphine (M) via a PCA system. A first dose of study medication was given 30 min prior to the estimated 'waking time' (first response to verbal command); a second dose was given 6 h later. M usage, pain intensity (rated by the patient using a VAS), nausea and sedation were regularly assessed up to 12 h post dose.

Results: The population had a mean age of 60 y; M/F=50%; 80% underwent hip replacement. A clear and statistically significant reduction in mean M usage was obtained after DKP.TRIS and T vs P (meanSD=1.71.0 and 1.60.8 vs 2.21.0 mg/h, respectively). Pain was well controlled (VAS<30) within the first 4, 6 and 10 h after DKP.TRIS, T and P respectively, with DKP.TRIS group obtaining the lowest pain scores from 2-12 h and less sedation than T group (77.8% vs 85.3%, ns). No difference in the overall AE profile, including nausea, was evident between treatments.

Conclusion: DKP.TRIS demonstrated a significant M sparing effect when used for the control of pain following major joint surgery. In combination with PCA M, a trend of superiority of DKP.TRIS vs T was observed in terms of time to obtain pain control as well as overall analgesic effect, with a lower degree of sedation.

Acknowledgments: Supported by grants from Menarini Ricerche S.p.A.

ANTI-INFLAMMATORY EFFECTS OF CELECOXIB AFTER INFERIOR INCLUDED THIRD MOLAR SURGERY
.P. Posso, J.O. Arantes, G. Neder, V.M. Medicine, Universidade de So Paulo, São Paulo, Brazil

Aim of investigation: To study the anti-inflammatory effect of COX2 inhibitor celecoxib.

Methods: It was evaluated 15 patients that had their inferior bilateral included third molar removed, one at a time (30 surgeries). Celecoxib or placebo were given to patients 3 hours before surgery. Group 1 received celecoxib before surgery and placebo right after it and group 2 had placebo before surgery and celecoxib right after it. Dipyrone was the rescue drug. The inflammation was evaluated by the mouth open measure between the incisal zone of superior and inferior incisors teeth. There were taken four measures: before surgery, right after, 24 and 48 hours after it.

Results: Before surgery the open mouth measure average to group 1 was 50.875.40 and to the group 2 was 50.624.20. Right after surgery the open mouth measure average to group 1 was 49.064.83 and to the group 2 was 49.125.11. 24 h after surgery the open mouth measure average to group 1 was 38.3514.21 and to the group 2 was 39.4312.98 and 48h after surgery the open mouth measure average to group 1 was 41.7812.84 and to the group 2 was 40.0312.95. There were no statistic relevant values in this study.

Conclusions: The use of celecoxib before inferior included third molar surgery does not change the inflammatory patterns.

Acknowledgments: Supported by FAPESP.

OPIOID-SPARING EFFECT OF ROFECOXIB COMPARED WITH DICLOFENAC IN ACUTE PAIN: A RANDOMIZED CONTROLLED TRIAL
D.J. Chang, E. Chen, A.B. Polis, M. McAvoy, S.H. Mockoviak, G.P. Geba Clinical Development, Merck & Co., Inc., West Pont, PA , Clinical Site Operations, SCIREX Corporation, Austin, TX

Aim of Investigation: To compare the opioid-sparing effect of rofecoxib and diclofenac in acute pain over 24 hours.

Methods: Patients experiencing moderate to severe pain after 3^rd molar surgery were randomized to rofecoxib 50 mg (1 dose), diclofenac sodium 50 mg q8 hours (3 doses), or placebo. Use of opioid rescue medication (hydrocodone/acetaminophen 5/500 mg) was recorded. Patients also rated their pain and global assessments throughout 24 hours.

Results: 305 patients were randomized to rofecoxib (N=121), diclofenac (N=121), or placebo (N=63). Fewer patients treated with a dose of rofecoxib required opioid medication than patients treated with a dose of diclofenac during 8 hours (19.8% vs 66.9%) and 3 doses of diclofenac during 24 hours (28.9% vs 76.0%). On average, rofecoxib patients required less opioid tablets than diclofenac patients during 8 hours (0.3 vs 1.0 per patient) and 24 hours (0.7 vs 1.9 per patient). Rofecoxib provided greater overall pain relief and patient global assessment scores than diclofenac over 8 and 24 hours. Rofecoxib patients achieved greater maximum analgesic effect, more rapid onset (31 minutes), and longer analgesic duration (>24 hours) than diclofenac patients. For all endpoints, the differences were significant (P<0.001).

Conclusion: Compared with diclofenac sodium 50 mgeither 1 dose over 8 hours or 3 doses over 24 hoursa single dose of rofecoxib 50 mg demonstrated a significant reduction in opioid use and provided greater analgesic efficacy.

Acknowledgement: Supported by Merck & Co., Inc. Authors Chang, Chen, Polis, McAvoy, Mockoviak, and Geba are employees of Merck & Co., Inc

EFFICACY AND SAFETY OF A SINGLE DOSE OF IV PARECOXIB SODIUM (PARE) FOLLOWED BY UP TO SEVEN DAYS OF ORAL VALDECOXIB (VALDE) FOR PAIN FOLLOWING LAPAROSCOPIC CHOLECYSTECTOMY
H. Minkowitz, T.J. Gan, R. Cheung, R. Hubbard, C. Chen, J.G. Fort, Dept of Anes, Memorial City Hospital, Houston, TX , ² Dept of Anes, University of Texas Southwest MCC, Dallas, TX , Dept of Anes, Duke University Medical Center, Durham, NC , ⁴ Global Medical Affairs, Pharmacia, Peapack, NJ , R&D, Pharmacia, Skokie, IL , ⁶ Global Health Outcomes, Pharmacia, Skokie, IL

Aim of Investigation: To evaluate a single preop dose of pare 40mg iv and postop oral valde 40 mg QD.

Methods: In this randomized, d-b, p-c trial pts received standard of care, fentanyl PRN in immediate postop period and APAP 500 mg/hydrocodone 5 mg po Q4-6H PRN following discharge for up to 7 days. The active arm also received pare 40mg iv 3045 min preop and valde 40mg QD po from 6-12h after surgery, for up to 7 days. "Worst Pain" was evaluated daily using a modified Brief Pain Inventory (mBPI).

Results: In immediate postop period (4H), pare pts (n=119) required significantly lower amounts of fentanyl (152.8g vs 192.9g: p=0.011) than comparator (n=104). Signif. fewer valde pts required supplemental analgesia over Days 1-5 postsurgery (p<0.02). Worst pain scores were also statistically signif. improved in valde group vs placebo. % pts reporting worst pain as none or mild (NRS4) in the valde and placebo group on Day 1 was 63.1% vs 29.2% (p<0.001); Day 2 69.2% vs 56.0% (p<0.02). Adverse events were comparable between groups.

Conclusions: Preop pare 40mg iv resulted in signif. opioid-sparing immediately following lap chole surgery. Valde 40mg QD provided signift opioid-sparing effects and reduced worst pain levels in these pts following discharge. Both pare and valde were well tolerated.

Disclosure: Sponsored by Pharmacia and Pfizer Inc.

TREATMENT OF CHRONIC LOW BACK PAIN WITH ETORICOXIB, A NEW CYCLO-OXYGENASE-2 SELECTIVE INHIBITOR: A 3 MONTH PLACEBO-CONTROLLED TRIAL.
G.P. Geba^, J. Adler E. Quaidoo4 R. Lipetz, R. Pallay, C. Skalky, K. O'Brien, N. Bohidar, Merck & Co., Inc., West Point, PA , Health First Medical Group, Fort Worth, TX , Clinicos, Colorado Springs, CO , AAIR Research Center, Rochester, NY , Encompass Clinical Research, Spring Valley, CA , Robert Wood Johnson, Belle Mead, NJ

Aim of Investigation: To evaluate the efficacy of etoricoxib (ETO) 60 mg and 90 mg for treatment of chronic low back pain (LBP).

Methods: The 325 patients received daily ETO 60 mg (n=109) or 90 mg (n=106), or placebo (PBO) (n=110) in a randomized, PBO-controlled 3 month trial. Patients were assessed at office visits at 1, 2, 4, 8, and 12 weeks. The primary endpoint was improvement from baseline in time-weighted average LBP Intensity Scale (0- to 100-mm Visual Analog Scale) at 4 weeks, also evaluated over 3 months with other outcome parameters.

Results: Demographics were similar among treatment groups. Patient mean age was 53 years. Average duration of LBP was 12 years. ETO 60 mg [-34.4 (CI: -38.7, -30.1)] and 90 mg [-32.3 (CI: -36.6, -27.9)] both demonstrated significant (P<0.001) improvement vs. PBO [-19.3 (CI: -23.5, -15.0)] for LBP intensity at 4 weeks, which was maintained over 3 months [-35.1 (CI: -39.6, -30.7), -35.7 (CI: -40.2, -31.2) vs. -23.0 (CI: -27.4, -18.6), respectively](P<0.001). Other endpoints including disability and bothersomeness scores paralleled pain relief.

Conclusions: In patients with chronic LBP, etoricoxib at doses of 60 and 90 mg daily provided significant efficacy in relief of pain and disability over 3 months. Improvement was observed as early as 1 week after initiation of therapy; plateaued at 4 weeks; and was maintained over the 3 month trial. All treatments were generally well tolerated.

Acknowledgments: Sponsored by Merck & Co., Inc.

INHIBITION OF CYCLO-OXYGENASE ENZYMES IN THE CENTRAL NERVOUS SYSTEM COULD EXPLAIN THE ANTI-NOCICEPTIVE EFFECT OF ACETAMINOPHEN IN MICE
S.S. Ayoub D.A. Colville-Nash, P.R. Botting, R.M., Experimental Pathology, The William Harvey Research Inst., London, United Kingdom

Aim of Investigation: To determine whether the mode of action of acetaminophen is through the inhibition of cyclo-oxygenase enzymes (COX-1 & 2) and whether the site of this effect is central or peripheral.

Methods: The writhing response was induced in C57Bl/6 mice (20-25g) by the intraperitoneal injection of either 0.6% acetic acid or 0.25g/10g iloprost and the number of subsequent writhes was counted for 20 min. The inhibitory effect of acetaminophen (150-400 mg/kg) and diclofenac (10-100 mg/kg), administered subcutaneously 30 min before the induction of writhing, was evaluated. Using enzyme immunoassays, prostaglandins were measured in peritoneal wash-outs from the acetic acid writhing. Currently we are measuring these mediators in brains and spinal cords of animals writhing to acetic acid and iloprost.

Results: Both acetaminophen (IC50 =172 mg/kg) and diclofenac (IC50 =17 mg/kg) dose-dependently inhibited acetic acid induced writhing. Interestingly, while acetaminophen also inhibited iloprost induced writhing (IC50 =108 mg/kg), diclofenac was without affect. We also found that while diclofenac dose-dependently reduced levels of prostacyclin in the wash-outs, acetaminophen did not reduce levels of either prostacyclin or PGE2.

Conclusions: Acetaminophen has a central site of action which is likely is to be dependent on inhibition of COX enzymes, whereas diclofenac inhibits peripheral COX.

Acknowledgements: Supported by a grant from the BBSRC.

A COMPARISON OF COX189, NAPROXEN AND PLACEBO FOR RELIEF OF POST-ORTHOPEDIC SURGERY PAIN
V. Chan1, J. Davis, R. Wolf, A. Forsythe D. Manning, S. Jayawardene ., Toronto, ON, Canada , Halifax, NS, Canada , ., Birmingham, AL , Novartis, EH, NJ

Aim of investigation: The analgesic efficacy and safety of COX189, a novel COX-2 selective inhibitor, was compared to naproxen and placebo in patients with post-surgical pain following total knee or hip arthroplasty.

Methods: Adult patients (n=180) with moderate to severe pain within 6hrs after stopping patient controlled analgesia (48hrs postsurgery), were randomized to receive COX189 400mg once daily, naproxen 500mg twice daily or placebo (60 per treatment group). Following the first administration of study medication, patients entered a 12hr single-dose analgesic evaluation, rating pain intensity (PI) on categorical and visual analog scales and pain relief on a categorical scale, at timepoints up to 12hrs or until rescue was taken. Patients then entered multiple-dose phase and rated pain intensity every 12hrs through 96hr timepoint. The primary efficacy variable was summed (time-weighted) pain intensity difference over the first 8hrs postdose (SPID-8). Safety was assessed via adverse events, vital signs and laboratory tests.

Results: For the primary variable, COX189 demonstrated a greater reduction in PI compared to placebo (p=0.009) with no statistically significant difference in analgesic effect from naproxen. The effectiveness of COX189 400mg was also evident during the multiple dose phase. COX189 had a similar safety profile to placebo and naproxen.

Conclusion: Over 5 days, COX189 400mg once daily was safe and effective in reducing moderate to severe post-surgical pain, and comparable to naproxen 500mg twice daily.

Acknowledgements: Supported by Novartis. Authors AF, SJ, DM are employees of Novartis.

MORPHINE SPARING EFFECT OF DEXKETOPROFEN TROMETAMOL WHEN USED IN THE TREATMENT OF POSTOPERATIVE PAIN AFTER MAJOR ABDOMINAL SURGERY
F. Miralles, A. Zapata, M. Mas, L. Borrs, M. Forns, R. Artigas, M. Puig, Anesthesiology Dep., Hospital Vega Baja, Orihuela, Spain , Clinical Research, Menarini Research, Barcelona, Spain , Anesthesiology Dep., Hospital del Mar, Barcelona, Spain

Aim of investigation: To compare the morphine-sparing effect, analgesic efficacy, and tolerability of intramuscular (i.m) dexketoprofen trometamol (DKT.TRIS, 25 and 50 mg) versus diclofenac (DIC, 75 mg) and placebo, in the treatment of postoperative pain after total abdominal hysterectomy and/or adnexectomy.

Methods:Multicenter, randomised, double-blind, parallel group trial. After informed consent , patients had surgery under balanced anesthesia. In recovery they received boluses of i.v. morphine as analgesic. Patients were included if they had a VAS>30 mm, and did not receive morphine in the previous 3 h (n=284). On inclusion, patients received one of the i.m. treatments and were connected to an i.v. PCA-morphine pump (1,5 mg bolus, lockout time 15 min). A second dose of i.m. treatment was given 8 h later. For a period of 20 h, the requirements of morphine (PCA), as well as other analgesic and safety parameters were evaluated.

Results: Demographic and clinical data were comparable at baseline between groups. Patients receiving 50 mg of DKP.TRIS required on average 45% less morphine than those receiving placebo (6,67.8 versus 11,911,3; p<0,001), an effect comparable to DIC-75 mg. No significant differences were observed between the DKP.TRIS 25 mg (10,29,5) and placebo. The incidence of AEs and treatment-related AEs were comparable between groups.

Conclusion: DKP.TRIS 50 mg significantly decreased the requirements of PCA-morphine, while no effect was observed after DKP.TRIS 25 mg. The analgesic efficacy of DKP.TRIS 50 mg was similar to that of DIC 75 mg.

EFFICACY OF COX189 COMPARED TO ROFECOXIB IN THE TREATMENT OF POSTOPERATIVE DENTAL PAIN: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL.
J. Fricke, Jr, S. Jayawardene, D. Manning, PPD Pharmaco Inc., Austin, TX , Novartis Pharmaceticals., East Hanover, NJ

Aim of investigation: To determine the analgesic efficacy and safety of COX189, a novel COX-2 selective inhibitor, at single oral doses of 200 mg (C200), 400 mg (C400) and 800 mg (C800) compared to 50 mg rofecoxib (R50) and placebo (Pl), following removal of 2 or more impacted third molars.

Methods: 259 Patients with severe/moderate pain within 5 hours post-surgery were randomized to receive C200 (n=52), C400 (n=52), C800 (n=52), R50 (n=51) or Pl (n=52). Efficacy was assessed via summed (time-weighted) pain intensity difference over the first 8 hours postdose (SPID-8; primary efficacy variable); time-specific pain intensity difference (PID), pain-relief (PR) and pain-relief intensity difference (PRID) based on categorical scales; time-to-onset of analgesia; time-specific PID based on a visual analog scale; total pain relief from 0-8 hours (TOTPAR-8); and patient global evaluation. Safety was assessed via adverse events, vital signs and laboratory tests.

Results: For SPID-8, C800, C400, C200 and R50 demonstrated superior analgesia compared to Pl. Based on PID-categorical, C800 and C400 showed statistical superiority to Pl from the 0.5 hour through 24 hours, while C200 and R50 were superior to Pl from 0.75 hour through 24 hours. The efficacy of the active treatments was confirmed by other variables. In general, both C400 and C800 were numerically better than R50. All active treatments were well tolerated.

Conclusions: COX189 is an effective, rapidly acting, and safe analgesic for the treatment of dental pain.

Acknowledgements: This study was supported by Novartis. Authors KZ, SJ, DM are employees of Novartis.

USEFULNESS OF ROFECOXIB FOR PAIN CONTROL AFTER BREAST AUGMENTATION
P. Duguay, G. Beauregard, M. Choinire, Institut de polychirurgie de Montral, Montreal, PQ, Canada , Plastic Surgery Service, Centre hospitalier de l'Universit de Montral, Montreal, PQ, Canada , Anesthesiology Dept, Centre hospitalier de l'Universit de Montral, Montreal, PQ, Canada

Aim of the investigation: To assess the efficacy of rofecoxib for controlling pain after breast augmentation.

Methods: Double-blind, randomized, placebo-controlled study in 77 patients (Mean age: 26.76.2 y) scheduled for augmentation mammaplasty. Patients received rofecoxib 50 mg or a placebo pill 1 hour before surgery and once a day for 7 days. Efficacy outcomes included opioid requirements, pain severity (0-10 intensity scale + impact on daily functioning (items of the Brief Pain Inventory)). Various adverse drug effects were measured including intraoperative bleeding and incidence of hematoma.

Results: There were no demographic differences between the Rofecoxib (R) (N=38) and Placebo (P) group (n=39). IV morphine requirements in the immediate postoperative period was significantly lower in the R-Group than in the P-Group (p=.05). Intake of combined codeine and acetaminophen in the 7 days following surgery was also significantly reduced in the R-Group (p=.01). Postoperative pain intensity scores both at rest and with effort were similar for both groups. Impact of pain on various aspects of daily functioning was also comparable in the two groups. No significant difference was observed for drug adverse effects except for the frequency of nausea which was slightly but significantly higher in the R-Group (p=.04).

Conclusions: Rofecoxib is a useful agent for pain treatment after breast augmentation and represents an interesting therapeutic avenue for pain control in plastic surgery.

Acknowledgement: Supported by the Fonds des plasticiens de lHtel-Dieu du CHUM

ASPIRIN IS EFFICACIOUS FOR THE TREATMENT OF SEVERE PAIN ASSOCIATED WITH MIGRAINE ATTACKS
L. MacEachern, D. Plaza, J. Quiring² R. Koslo, Clinical Affairs, Bayer Corporation, Morristown, NJ , QST Consultations, Allendale, MI

Aim of Investigation: To evaluate the efficacy of Extra Strength Bayer Aspirin in the treatment of severe pain in patients with migraine attacks.

Methods: An analysis of a sub-population of subjects with severe migraine headache pain at baseline was conducted in this prospective, randomized, double-blind, parallel-group, single-dose study which compared the efficacy of 2 Extra Strength Bayer Aspirin (ASA, 1000 mg total) to placebo. Efficacy was evaluated for this subset analysis in 153 subjects (ASA 80, Placebo 73) over the age of 18 who met IHS criteria for migraine with or without aura, and who presented with severe pain at baseline. At 30 minutes, 1, 2, 3, 4, 5, and 6 hours after dosing, subjects evaluated pain intensity as none, mild, moderate, or severe. Severity of symptoms of photophobia, phonophobia and functional ability was assessed. The primary variable was the percent of responders at 2 hours; responders were defined as subjects who experienced a reduction in pain from severe to mild or none.

Results: ASA was significantly more effective than placebo for percent responders at 2 hours with a 48% response rate vs 26% (p=0.008). At 2 through 6 hrs post-dose migraine symptoms of photophobia (p< 0.023), phonophobia (p<0.007) and functional ability (p<0.001) were significantly improved. Pain Intensity Difference evaluations at 2 through 6 hrs (p<0.006), were significantly better in the aspirin group and SPID at 6 hours (p< 0.001). ASA was comparable to placebo for all safety evaluations.

Conclusions: Extra Strength Bayer Aspirin is an effective treatment for severe migraine.

Acknowledgements: L. MacEachern, D. Plaza & R. Kolso are employees of Bayer Corporation. J. Quiring is a consultant for Bayer

10th World Congress on Pain, List of topics

10th World Congress on Pain. International Association for the Study of Pain, San Diego, California, USA August 17-22, 2002