Efficacy and safety of deracoxib for control of postoperative pain and inflammation associated with soft tissue surgery in dogs.

OBJECTIVE: To investigate the effectiveness and safety of deracoxib (Deramaxx®) administered at a dose of 1-2 mg/kg/day for 3 days for control of postoperative pain and inflammation associated with soft tissue surgery in dogs. STUDY DESIGN: Prospective, randomized, blinded, placebo-controlled, multi-center clinical study. ANIMALS: Dogs (n = 34). METHODS: Dogs undergoing soft tissue surgeries were randomly assigned to receive either deracoxib (n = 18) or placebo (n = 16) as a preoperative treatment and again once daily for 2 additional days after surgery unless removed from the study. Dogs were evaluated before surgery and again postsurgically at predetermined times using the Glasgow Composite Pain Scale (GCPS). All dogs were allowed to receive another pain medication (except nonsteroidal anti-inflammatory drugs [NSAIDs] or corticosteroids) as postsurgical pain intervention if the dog scored ≥6 on the GCPS or was in obvious discomfort. Dogs receiving pain intervention were considered treatment failures and were removed from the study. RESULTS: Two of 16 dogs treated with deracoxib were rescued compared with 9 of 16 dogs receiving placebo (P = .0091). In addition, deracoxib treated dogs had numerically lower GCPS scores. CONCLUSIONS: Results suggest perioperative administration of deracoxib to dogs at 1-2 mg/kg/day for 3 days significantly improves analgesia in the postoperative surgical period after soft tissue surgery. Placebo dogs not rescued after painful procedures highlight the need for refinement of current pain assessment tools.

Efficacy and safety of deracoxib for the control of postoperative pain and inflammation associated with dental surgery in dogs.

The efficacy and safety of deracoxib administered at 1-2 mg/kg/day for 3 days was assessed for the control of postoperative pain and inflammation associated with dental surgery in dogs. Client-owned dogs scheduled for dental extractions were premedicated with butorphanol and randomly assigned to receive either deracoxib (n = 31) or placebo (n = 31) preoperatively and again once daily for 2 additional days. Dogs were evaluated prior to and after surgery using a modified Glasgow Composite Pain Scale (mGCPS). Dogs could be rescued at any time if they scored ≥4 on the mGCPS or in cases of obvious discomfort. Rescued dogs were considered treatment failures for determining treatment response and were removed from the study. Of the 62 dogs enrolled, 57 were usable for the efficacy analyses and all were assessed for safety. Four of 27 deracoxib-treated dogs (14.8%) were rescued compared to 20 of 30 placebo dogs (66.7%) (P = 0.0006). Deracoxib-treated dogs also had numerically lower mGCPS scores. Eight of 31 deracoxib dogs (26%) had adverse events reported compared to 6 of 31 placebo dogs (19%). Results indicate perioperative administration of deracoxib to dogs at 1-2 mg/kg/day for 3 days significantly improves analgesia after dental surgery.

Evaluation of a digitally integrated accelerometer-based activity monitor for the measurement of activity in cats.

OBJECTIVE: To assess the correlation between data generated by an accelerometer-based activity monitor and the distance moved in cats. STUDY DESIGN: Prospective experimental study. ANIMALS: Three, four-year-old, male, purpose-bred research cats, weighing between 5.1 and 5.9 kg. METHODS: Part I: Collar and harness mounted accelerometers were evaluated in three cats, comparing simultaneously collected accelerometer data with movement data from computer-analyzed video. Part II: Cats wore collar and harness mounted accelerometers, and data were recorded for 4 weeks to evaluate day-to-day and week-to-week variation in activity. RESULTS: Part I: 432 hours of simultaneous video and accelerometer data were collected. The correlation between accelerometer counts and distance moved was 0.82 overall. Agreement between collar and harness mounted accelerometers was excellent with only 6% of the differences in measurements lying outside the mean difference +/- 2 standard deviations. The adjusted R(2) for harness accelerometer output and 6% mobility was 0.75; for movement 0.84; and for mean velocity 0.83. Evaluation of video indicated eating, grooming and scratching created high accelerometer counts with little effect on movement. Part II: There was a significant effect of day on harness (p < 0.001) and collar (p < 0.002) counts, with counts being lowest at the weekend. There was a significant effect of week on harness-mounted accelerometer counts (p < 0.034), but not on collar-mounted accelerometer counts. Harness accelerometer counts were lowest in week 1. CONCLUSION: Output from an acceleration-based digitally integrated accelerometer correlated well with distance moved and mobility in freely moving cats provided the mobility threshold in the analysis software was > or = 6%. CLINICAL RELEVANCE: Acceleration-based activity monitors may allow for objective measurement of improved mobility following analgesic treatment for conditions such as osteoarthritis.

Evaluation of client-specific outcome measures and activity monitoring to measure pain relief in cats with osteoarthritis.

BACKGROUND: There are no validated systems for measuring pain from osteoarthritis in cats. HYPOTHESIS: Owner subjective assessments and an activity monitor (AM) can be used to detect pain in cats with osteoarthritis and to assess efficacy of treatments. ANIMALS: Thirteen cats older than 10 years old, with owner-assessed decreases in activity, painful arthritic joints, and clinically normal blood work were included and evaluated for 3 weeks. METHODS: A collar-mounted AM measured activity and a client-specific outcome measure (CSOM) questionnaire characterized the severity of impairment. Overall global quality of life was also evaluated for each treatment. In weeks 2 and 3, meloxicam (0.1 mg/kg, day 1; 0.05 mg/kg, days 2-5) or a placebo was administered in a blinded, randomized, cross-over manner to test the assessment systems. RESULTS: The cats had a median of 4 arthritic appendicular joints. Activity counts for the week when cats (complete data on activity; n=9) were administered meloxicam were significantly higher than at baseline (P = .02) but not after placebo (P = .06). Baseline activity counts were not significantly different from placebo (P = .6). The CSOM data (n=13) showed that owners considered their cats to be more active on meloxicam compared with baseline (P = .001) and placebo (P < .004), and more active on placebo than at baseline (P < .01). Global quality of life improved significantly with meloxicam (P < .042). CONCLUSIONS AND CLINICAL IMPORTANCE: Both an AM and a CSOM system can detect behavior associated with pain relief in cats that are arthritic. Objective activity data might allow subjective assessment systems to be validated for use in clinical studies.

Biomechanical comparison of dual interlocking single loop and double loop tension band techniques to the classic AO tension band technique for repair of olecranon osteotomies in dogs.

OBJECTIVE: To compare olecranon fragment stability between the classic tension band wire (TBW) technique with the wire placed either in contact with (Arbeitsgemeinschaft für Osteosynthesefragen [AO]), or not in contact with, a Kirschner (K)-wire (AOW) to 2 novel wire patterns: a dual interlocking single loop (DISL) and a double loop (DL). STUDY DESIGN: Ex vivo mechanical evaluation on cadaveric bones. SAMPLE POPULATION: Canine ulnae (n=40) with olecranon osteotomies repaired with 2 K-wires and 1 of 4 TBW constructs. METHODS: Single load to failure applied through the triceps tendon. Displacement was measured from images captured from digital video. Techniques were compared based on the load resisted when the olecranon fragment was displaced 0.5, 1, and 2 mm. RESULTS: At 0.5 mm of displacement, the DISL construct resisted more load than the AOW construct (505 versus 350 N; P=.05). AO and DL constructs resisted an intermediate load (345 and 330 N, respectively). There was no significant difference between groups at 1 mm of displacement. At 2 mm of displacement, DL (785 N) resisted more load than AO (522 N, P=.01) and AOW (492 N, P=.03) groups. CONCLUSIONS: DISL constructs provided similar stability to classic TBW constructs whereas DL constructs were more stable at higher loads. CLINICAL RELEVANCE: The DL construct is easy to perform, less bulky, and provides comparable fragment stability to standard TBW techniques at functional loads. Surgical method is important for optimal performance of all TBW constructs.

Pharmacogenetic analysis of sex differences in opioid antinociception in rats.

Sex differences in opioid antinociception have been reported in rodents and monkeys, with opioids being more potent in males than females. In the present study, the influence of rat strain on sex differences in opioid antinociception was examined in a warm water tail-withdrawal procedure. Antinociceptive tests were conducted with the high-efficacy micro-opioid morphine, and the less efficacious opioids buprenorphine, butorphanol and nalbuphine. Baseline nociceptive latencies were consistently higher in males than their female counterparts. Sex differences in opioid antinociception were observed in all strains tested, with the opioids being more potent and/or effective in males. The magnitude of the sex differences was related to the relative efficacy of the opioid, with morphine, buprenorphine, butorphanol and nalbuphine being on average 2.2-, 2.6-, 15.9- and 11.9-fold more potent in males. Sex differences also varied markedly across strains, with large differences consistently obtained in the F344 and F344-Sasco strains, moderate differences in the ACI, DA, Lewis, Sprague Dawley, Wistar and Wistar-Kyoto strains, and small differences in the Long Evans-Blue Spruce, Long Evans, Brown Norway and Holtzman strains. When compared across strains, there was no relationship between sex differences in nociceptive sensitivity and opioid sensitivity. These findings provide strong support for the role of genetic factors in determining sex differences in opioid antinociception, and suggest that the use of low-efficacy opioids, coupled with the use of rat strains that display small and large sex differences in opioid antinociception, may provide a sensitive tool to investigate the mechanisms underlying sex differences in opioid antinociception.

Capsaicin-induced hyperalgesia and mu-opioid-induced antihyperalgesia in male and female Fischer 344 rats.

The influence of sex in determining responses to opioid analgesics has been well established in rodents and monkeys in assays of short-lasting, phasic pain. The purpose of this investigation was to use a capsaicin model of tonic pain to evaluate sex differences in hyperalgesia and mu-opioid-induced antihyperalgesia in Fischer 344 (F344) rats. Capsaicin injected into the tail produced a dose-dependent thermal hyperalgesia in males and females, with the dose required to produce a comparable level of hyperalgesia being 3.0-fold higher in males than in females. These sex differences were modulated by gonadal hormones, inasmuch as gonadectomy increased the potency of capsaicin in males and decreased its potency in females. Morphine, buprenorphine, and dezocine administered by various routes [systemic (s.c.), local (in the tail), and central (i.c.v.)] generally produced marked antihyperalgesic effects in males and females. Although in most instances these opioids were equally potent and effective in males and females, selected doses of local and i.c.v. administered buprenorphine produced greater effects in females. When administered locally, the antihyperalgesic effects of morphine were mediated by peripheral opioid receptors in both males and females, since this effect was not reversed by i.c.v. naloxone methiodide. These data contrast with the finding that mu-opioids are more potent in male rodents in assays of phasic pain, thus suggesting that distinct mechanisms underlie male and female sensitivity to opioid antinociception in phasic and tonic pain models. These findings emphasize the need to test male and female rodents in tonic pain assays that may have greater relevance for human pain conditions.

Use of irreversible antagonists to determine the relative efficacy of mu-opioids in a pigeon drug discrimination procedure: comparison of beta-funaltrexamine and clocinnamox.

The use of irreversible antagonists to assess opioid efficacy has proven fruitful for classifying opioids on the basis of high or low efficacy, but few studies have provided quantitative estimates of efficacy. The purpose of this study was to use beta-funaltrexamine (beta-FNA) and clocinnamox (C-CAM) in a drug discrimination procedure to examine the efficacy of fentanyl, morphine, l-methadone, sufentanil, and etorphine. In pigeons trained to discriminate 0.12 mg/kg fentanyl from water, dose-effect curves were determined for each opioid alone and after pretreatment with beta-FNA and C-CAM. Using quantitative analyses according to an extended model of Black and Leff (1983), apparent efficacy (tau) and affinity (KA) of each opioid was determined, as well as the degree of receptor inactivation (q) produced by each dose of each antagonist. beta-FNA and C-CAM produced dose- and time-dependent, rightward shifts in the dose-effect curves of each opioid, and analyses based on dose-ratios and tau values suggest a rank order of efficacy of etorphine > sufentanil = l-methadone > fentanyl = morphine. Marked differences in the profiles of antagonism produced by beta-FNA and C-CAM were also apparent, as C-CAM, but not beta-FNA, produced insurmountable antagonism. The q values for each antagonist were consistent with these data in indicating that C-CAM and beta-FNA can inactivate nearly 100 and 75% of the receptor population, respectively. In tests conducted in pigeons chronically treated with morphine, doses of beta-FNA that produced parallel, rightward shifts in untreated pigeons flattened the morphine dose-effect curve in morphine-treated pigeons. These results indicate that beta-FNA and C-CAM can differentiate opioids with high relative efficacy and yield comparable estimates of efficacy for various opioids. There are, however, limitations in the proportion of the receptor population that can by eliminated by beta-FNA.

Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats.

Previous studies indicate that in antinociceptive procedures employing thermal, chemical and electrical stimuli, opioids are generally more potent in male than female rodents. The purpose of the present study was to examine nociception and opioid antinociception in male and female rats using a mechanical nociceptive stimulus. Results indicated that males had a higher threshold for nociception, and in tests in which a constant pressure was applied to the hindpaw, the paw withdrawal latencies were consistently longer in males. Opioids with activity at the mu receptor, including levorphanol, morphine, dezocine, buprenorphine, butorphanol and nalbuphine, were generally more potent and/or effective in males. In contrast, sex differences were not consistently observed with the kappa-opioid receptor agonists spiradoline, (5,7,8b)-N-methyl-N[2-1(1-pyrrolidinyl),1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U69593), trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide (U50488), enadoline, ethylketocyclazocine, and nalorphine. These findings suggest that males and females differ in their responsiveness to mechanical nociception and that sex differences in sensitivity to kappa-, but not mu-, opioid receptor agonists are specific to certain nociceptive stimulus modalities.