T142 DOES WOUND INFILTRATION OF TRAMADOL REDUCE POSTOPERATIVE PAIN IN LAPAROSCOPIC OR OPEN HERNIOGRAPHY?

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POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295

T139 Pha1b TOXIN PREVENTS PERIPHERAL AND SPINAL CAPSAICIN-INDUCED NOCICEPTION IN RATS AND CALCIUM TRANSIENTS IN TRPV1-HEK293 CELLS AND DRG NEURONS M.V. Gomez1,2 *, F. Juliano3 , J. Milano1 , C.J. Castro Junior1 , A.H. Souza2 , M.A.R. Silva2 , M.N. Cordeiro4 , M. Richardson4 , M.A.M. Prado5 , V.F. Prado6 . 1 Nucleo de P´ os Graduac˜ ¸ ao, Hospital Santa Casa de Belo Horizonte, 2 Laboratorio de Neurociˆencia, Faculdade de Medicina UFMG, Belo Horizonte, 3 Toxicology, Universidade Federal de Santa Maria RGS, Santa Maria, 4 Bioquimica, Fundac˜ ¸ ao Ezequiel Dias, Belo Horizonte, Brazil; 5 Anatomy and Cell Biology, University Western Ontario, London, 6 Physiology and Pharmacology, University Western Ontario, Londom, ON, Canada Background and Aims: Pha1b blocks VSCCs and abolishes capsaicin-induced calcium influx and glutamate release in rat spinal cord synaptosomes, suggesting a role for TRPV1 in its analgesic action. We investigate the effect of Pha1b in capsaicin-induced pain and mechanical allodynia in rats and its effect in capsaicininduced calcium transients in heterologous (TRPV1-HEK293 cells) and native DRG neurons. Methods: The i.d. and i.t. injections in rats were performed according Souza et al, 2008. DRG neurons obtained from adult male Wistar rats. HEK cells transfected with the human vanilloid receptor 1 were a gift from Dr. John B Davis. Calcium fluorescence imaging using 3mM Fluor 4-AM performed in a Leica SP5 laser scanning confocal system. Binding assays were carried out as described by Andre et al., 2004. Results: Pretreatment with Pha1b i.d. or i.t, reduced nociception and mechanical allodynia induced by peripheral and spinal capsaicin exposure in rats. The selective antagonist of the TRPV1 receptor, SB366791 similarly prevented capsaicin-induced nociception and mechanical allodynia. w-conotoxin MVIIA, was ineffective on capsaicin-induced nociception. Capsaicin-induced calcium influx in DRG neurons and HEK cells expressing TRPV1 was also inhibited by Pha1b and SB366791. The inhibitory actions of Pha1b and SB366791 on capsaicin-induced calcium transients in DRG neurons were not additive, suggesting they act on the same pathway. Neither Pha1b nor SB 366791 altered the binding of [3 H]resiniferatoxin in rat DRG membranes. Conclusions: The results demonstrate that the Pha1b prevents capsaicin-induced nociception using a TRPV1 pathway but without binding directly to this receptor. Supported INCT-CNPq, Fapemig and Capes Disclosure: We have patent for the use of the toxin Phalfa1beta in pain

T140 EFFECT OF ORAL & INTRAMUSCULAR INJECTION OF METHOCARBAMOL AND PLACEBO ON MUSCLE STRAIN PAIN P. Yazdanpanah1 *, M. Nikbakht2 , S. Kheramin3 , R. Hossini4 . 1 Physical Medicine & Rehabilitation, 2 Pharmacology, 3 Psychology, 4 Emergency Ward, Yasouj University of Medical Sciences, Yasouj, Iran Background and Aims: Muscle strain is caused by overstretching and /or partial or complete tear in musculo-tendinous junction. The aim of this study was survey the effect of oral and intramuscular injection of methocarbamol and placebo on muscle strain pain. Methods: This was a clinical trial study which was performed from June 2008 to March 2010. 120 patients with diagnosis of muscle strain with duration of less than 2 weeks were classified by randomized allocation in 3 groups with equal numbers. The demographic informations and pain intensity were evaluated before starting and at the end of treatment. The first group received oral methocarbamol (2 tab (1000 mg), q4h, for 3 days, then 3 tab, q8h, for 4 days) and naproxen (1 tab (500 mg), q12 h for 7 days). The second group received 1 ampule (1000 mg) methocarbamol on buttocks and naproxen (1 tab (500 mg), q12 h for 7 days). The third group received placebo (1 tab, q12 h) and naproxen (1 tab (500 mg), q12 h) for 7 days.

Results: The mean pain severities before treatment were a 4.64, 4.26, and 4.16 in 3 group respectively that was not significant. The mean pain severities after end of treatment were 2.12, 2.16, and 1.57 in 3 groups respectively that was not significant. The mean pain severities before and after end of treatment were 4.49 and 1.95 that was significant. Conclusions: The pain severity was decreased in 3 groups. The pain reduction was more in patients who received placebo. These findings suggest that pain reduction was due to effect of naproxen and lapse of time. Disclosure: None declared

T141 MULTI-DAY ANALGESIA WITH ETORICOXIB FOLLOWING THIRD-MOLAR EXTRACTION SURGERY USING A FLEXIBLE DOSING PARADIGM J. Brown1 , S. Daniels2 , A. Gammaitoni3 *, P.M. Peloso3 , M. Losada3 , S.S. Smugar3 , A. Mehta3 , A.T. Ko3 . 1 Jean Brown Research, Salt Lake City, UT, 2 Premier Research Group, Austin, TX, 3 Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA Background and Aims: We evaluated a multiday flexible dosing paradigm with etoricoxib following oral surgery. Methods: This double-blind, randomized controlled study compared etoricoxib 90 mg and 120 mg with placebo, ibuprofen 600 mg qid, or acetaminophen 600 mg/codeine 60 mg (A/C; qid) in patients with ≥2 third-molar extractions (≥1 impacted). Patients dosed as needed (flexible dosing on Days 2 and 3 with study (SM) and rescue medication (RM; acetaminophen 325 mg). Outcomes included average and worst recall pain (0–10 scale), RM, total SM doses used (days 1–3), and adverse experiences (AE). Results: Differences from placebo for Average and Worst Recall Pain are shown (Table). RM usage was 57% (placebo) and 18–23% across active treatments on Day 2, and 22% (placebo) and 14–20% across active treatments on Day 3. The mean numbers of SM doses were 2.02, 1.52, 1.74, 2.32, and 1.59 on Day 2 and 0.80, 1.08, 1.07, 1.65, and 1.25 on Day 3 for placebo, etoricoxib 120 mg, etoricoxib 90 mg, ibuprofen, and A/C, respectively. A/C had more AEs and less dosing. On Day 2, placebo and ibuprofen patients took more SM and RM than etoricoxib and had worse pain. Nausea and vomiting were common AEs with higher frequency with A/C. Conclusions: Etoricoxib provided better treatment responses compared with ibuprofen and A/C and resulted in less dosing vs. ibuprofen on Days 2 and 3. Table: Differences from placebo in Average and Worst Recall Pain scores

Average Recall Pain Day 2 Day 3 Worst Recall Pain Day 2 Day 3

Etoricoxib 120 mg qd

Etoricoxib 90 mg qd

Ibuprofen 600 mg qid

Acetaminophen 600 mg/ codeine 60 mg qid

−1.40 −0.68

−1.29 −0.78

−1.11 −0.28

−0.97 −0.45

−1.42 −0.37

−0.97 −0.78

−0.79 −0.21

−0.48 −0.62

Disclosure: JB and SD were investigators in the study, which was sponsored by Merck. AG, PMP, ML, SSS, AM, ATK are employees of Merck and may own stock/stock options in the company.

T142 DOES WOUND INFILTRATION OF TRAMADOL REDUCE POSTOPERATIVE PAIN IN LAPAROSCOPIC OR OPEN HERNIOGRAPHY? R. Sivaci1,2 *, E. Eroglu3 , S. Yilmaz4 , L. Yavuz5 , F. Eroglu5 , Y. Sivaci6 . 1 Anesthesiology and Reanimation, 2 Afyon Kocatepe University Medical School, Afyon, 3 General Surgery, Suleyman Demirel University, Isparta, 4 General Surgery, Afyon Kocatepe University Medical School, Afyon, 5 Anesthesiology and Reanimation, Suleyman Demirel University, Isparta, 6 Pulmonary Hospital, Afyon, Turkey Background and Aims: Tramadol is a centrally acting synthetic analgesic with m-opioid receptor agonist activity, it is a widely

POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295

prescribed analgesic used in the treatment of moderate to severe pain and as an alternative to opiates. Tramadol causes less respiratory depression than morphine at recommended doses. Its efficacy and low incidence of side effects lead to its unnecessary prescribing in patients with mild pain. The aim of this study was to evaluate the effects of laparoscopic or tension free open herniography when tramadol administration at wound closure on postoperative pain and analgesic requirements under spinal anesthesia. Methods: Twenty patients were randomized into two groups (n = 10 in each) to either laparoscopic herniography (LH) or tension free open herniography (TFOH). Patients received wound closure infiltration of 200 mg tramadol in 40 mL of 0.9% saline solution. Postoperative pain was assessed with a Visual Analog Scale (VAS) at 3, 6, 12, and 24 hours postoperatively. The consumption of tramadol was registered. Results: We observed lower VAS scores and higher need for supplementary analgesics for the patients in LH group than TFOH group (p < 0.05). Conclusions: We conclude that tramadol 200 mg has local analgesic effect on postoperative pain after TFOH. Disclosure: None declared

T143 PERIOPERATIVE USE OF ETORICOXIB IMPROVES PATIENT RECOVERY IN PATIENTS UNDERGOING TOTAL ABDOMINAL HYSTERECTOMY E. Viscusi1 , R.A. Black2 , R. Sinatra3 , P.M. Peloso4 , A.T. Ko4 , A. Mehta4 , S.S. Smugar4 , L. Morgan4 , A. Gammaitoni4 *, D.A. Papanicolaou4 , T.L. Frenkl4 , S.F. Butler2 . 1 Thomas Jefferson University, Philadelphia, PA, 2 Inflexxion, Newton, MA, 3 Yale University, New Haven, CT, 4 Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA Background and Aims: To determine of the effect of perioperative etoricoxib use on patient-reported post-operative recovery from total abdominal hysterectomy (TAH). Methods: This multicenter, double-blind, placebo-controlled study included patients undergoing open abdominal hysterectomy. Study medication (placebo, etoricoxib 90 or 120 mg) was administered 1–2 hours preoperatively and daily for the first 5 days following surgery. Patients were also provided IV PCA morphine and oral opioids as required. The primary efficacy endpoint was Pain at Rest over Days 1–3 (0–10 NRS scale). Patients also completed a 22-item Opioid Side Effects Scale of the Recovery Index-49 (RI-49) on Days 2–5. Morphine use and time to first flatus were also monitored. Results: 430 patients were evaluated, randomized to placebo (P), n = 144; etoricoxib 90 mg (E90), n = 142; or etoricoxib 120 mg (E120), n = 144. Etoricoxib patients reported significantly lower Pain at Rest Scores over Days 1–3 compared with placebo (p < 0.001). Total daily dose of morphine (mg) over days 1–3 were 7.75 (P), 5.46 (E90), and 5.37 (E120), (p < 0.001). Patient-reported times (hours) to first flatus were 43.99 (P), 35.42 (E90), and 33.14 (E120). The RI49 Opioid Side Effects Scale scores were lower for both etoricoxib groups compared with placebo; p < 0.05 with scores 3.71 to 7.20 units lower than placebo over Days 2–5. Conclusions: In this study, perioperative use of etoricoxib 90 and 120 mg significantly reduced pain intensity and morphine use in patients undergoing open TAH. The RI-49 Opioid Side Effects Scale captured clinically meaningful reductions in opioid-associated adverse effects. Disclosure: EV was an investigator in this study, which was sponsored by Merck. RAB and SFB were consultants on this study; RS has no disclosures or conflicts; PMP, ATK, AM, SSS, LM, AG, DAP & TLF are employees of Merck and may own stock/stock options in the company.

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T144 ANTIINFLAMMATORY AND ANALGESIC EFFECT OF DIETARY SUPPLEMENTATION WITH OMEGA-3 FATTY ACID, IN RATS I.P. Posso1,2 *, T.R. Mesquita3 , E. Constantino2 , V.R. Leite4 , M.B.S. Posso5 , O.C. Pires2 . 1 Cirurgia, Universidade de S˜ ao Paulo, S˜ ao Paulo, 2 Ciencias Basicas, Universidade de Taubate, Taubate, 3 Ciencias Basicas, Universidade de Taubate, S˜ ao Paulo, 4 Anaesthesiology, Hospital Universitario de Taubate, Taubate, 5 Nursing, Universidade do Vale do Paraiba, Sao Jose dos Campos, Brazil Background and Aims: Studies have shown beneficial effects of omega-3 fatty acids on health, including antiinflammatory action to reduce the synthesis of arachidonic acid derivatives. The study aimed to demonstrate the analgesic and antiinflammatory dietary supplementation with omega-3 fatty acid compared with tenoxicam. Methods: After approval from the Ethics Committee we included 18 male Wistar rats weighing between 220 and 300 grams; they were divided into three groups (n = 6): control, tenoxicam and omega-3, which received over 15 days respectively saline 0.2 mL, tenoxicam 1 mg·kg−1 ·day−1 and omega-3 fatty acid 200 mg·kg−1 ·day−1 . Pain was induced by the formalin test. Statistical analysis by ANOVA and Dunnett’s tests. Results: Regarding the phases of the formalin test, the groups tenoxicam and omega 3 were similar statistically. Nevertheless, showed less painful response in the second phase of testing when compared with the control group (p < 0.05). The response in phase I of the formalin test is attributed to direct activation of nociceptors, whereas phase II is associated with release of local endogenous mediators that generate an inflammatory response, responsible for sensitization of primary afferent and spinal sensory neurons. In this study we observed antiinflammatory effect of dietary supplementation with omega-3 fatty acid compared with tenoxicam. Conclusions: The results showed anti-inflammatory and analgesic effects of omega-3 fatty acid in rats, suggesting that dietary supplementation with omega-3 fatty acid may be useful in chronic inflammatory processes, where the use of anti-inflammatory drugs is related to increased morbidity. Disclosure: None declared

T145 METFORMIN AND PHENFORMIN BLOCK THE PERIPHERAL ANTINOCICEPTION INDUCED BY DICLOFENAC AND INDOMETHACIN ON THE FORMALIN TEST ´ rea Acad´emica de Medicina del Instituto de Ciencias M.I. Ortiz1,2 *. 1 A de la Salud de la Universidad Aut´ onoma del Estado de Hidalgo, 2 Hospital del Ni˜ no DIF, Pachuca Hidalgo, Mexico Background and Aims: Evidences have shown that systemic administration of sulfonylureas and biguanides blocks the diclofenac-induced antinociception, but not the produced by indomethacin. However, there is no any report about the peripheral interaction between diclofenac and the biguanides. Therefore, this work was undertaken to determine whether glibenclamide, glipizida, metformin and phenformin have any effect on the peripheral antinociception induced by diclofenac and indomethacin. Methods: Diclofenac and indomethacin were administrated locally in the formalin-injured paw and the antinociceptive effect was evaluated using the 1% formalin test. To determine whether peripheral antinociception induced by diclofenac or indomethacin was mediated by either the ATP-sensitive K+ channels or biguanides-induced mechanisms, effect of pretreatment with the appropriates vehicles or glibenclamide, glipizide, metformin and phenformin on the antinociceptive effect induced by local peripheral diclofenac and indomethacin was assessed. Results: Local peripheral injections of diclofenac (50–200 mg/paw) and indomethacin (200–800 mg/paw) produced a dose-dependent