Effect of deracoxib,a new COX-2 inhibitor,on the prevention of lameness induced by chemical synovitis in dogs

Twenty-four healthy, mixed-breed hound-type dogs were evenly and randomly assigned to a placebo control group, one of four dosages of deracoxib (0.3, 1, 3, or 10 mg/kg), or carprofen (2.2 mg/kg). Oral dosing of placebo, carprofen, or deracoxib was done 30 minutes before intraarticular injection of urate crystal suspension for induction of synovitis. Ground reaction forces, subjective clinical lameness scores, pain, joint effusion, and quantitative pain threshold responses were measured in a blinded fashion before induction of synovitis and 2, 4, 6, 8, 12, and 24 hours after injection. The medium and high dosages of deracoxib were effective in preventing lameness and pain associated with synovitis. Carprofen was also somewhat effective in attenuating the severity of urate-induced synovitis but to a lesser degree than the medium dose of deracoxib. Preemptive deracoxib treatment at dosages as low as 1 mg/kg reduced lameness and pain of synovitis associated with intraarticular administration of urate crystals.     

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis

OBJECTIVE: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. RESULTS: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.     

Evaluation of analgesia provided by the administration of epidural ketamine in dogs with a chemically induced synovitis

OBJECTIVE: To determine if epidural ketamine provides analgesia in dogs with a chemically induced synovitis. STUDY DESIGN: Prospective randomized experimental trial. ANIMALS: Thirty-two healthy, adult mongrel dogs (13-30 kg). METHODS: (Part I) Synovitis was induced in the right stifle of 16 dogs and allowed to develop for 12 hours. Epidural injection at the lumbosacral space of either ketamine (2 mg kg(-1); n = 8) or placebo (n = 8) was performed. Limb use and pain were measured using a force platform and numerical rating scale (NRS). Assessments were performed before and at 12, 14, 16, 18, 20, and 24 hours after the induction of synovitis. (Part II) Epidural injection of either ketamine (n = 8) or placebo (n = 8) was performed immediately before the induction of synovitis. Analgesia was assessed as in Part I. Assessments occurred before and at 2, 4, 6, 8, and 12 hours after the induction of synovitis. RESULTS: (Part I) Vertical ground reaction forces (VGRF) significantly decreased and NRS scores of total pain significantly increased after the induction of synovitis in all dogs (p < 0.05). No significant differences in VGRF or NRS scores were measured between treatment groups at any assessment period. (Part II) Dogs that received ketamine had significantly lower NRS scores 2 hours after treatment (p < 0.05). NRS scores did not differ between groups at any other evaluation. VGRF did not differ significantly between treatment groups at any assessment period. CONCLUSION: Epidural ketamine at a dose of 2 mg kg(-1) administered after the development of synovitis does not provide significant levels of analgesia. Administration of ketamine before the induction of synovitis significantly decreased the NRS score 2 hours post-induction. CLINICAL RELEVANCE: Administration of epidural ketamine before tissue injury may provide analgesia of short duration in dogs.     

Kinetic gait and subjective analysis of the effects of a tachykinin receptor antagonist in dogs with sodium urate-induced synovitis

OBJECTIVE: To examine the ability of preemptive administration of a proprietary neurokinin-1 (NK(1)) receptor antagonist to attenuate limb dysfunction associated with monosodium urate-induced synovitis in the stifle joints of dogs. ANIMALS: 16 clinically normal adult mixed-breed dogs (8 males and 8 females). PROCEDURES: A crossover study was conducted in 2 phases. Dogs were assigned to 2 groups (8 dogs/group) and orally administered an NK(1) receptor antagonist (3 mg/kg) or a control substance once daily for 4 days. Synovitis was then induced in the left stifle joint by intra-articular injection of monosodium urate. Investigators were not aware of treatment group assignments. Dogs were evaluated by use of subjective lameness scores during standing, walking, and trotting and by use of ground reaction force data 3, 6, 9, 12, and 24 hours after urate injection. After a 21-day washout period, the experiment was repeated with each dog administered the other treatment and injected with monosodium urate in the contralateral stifle joint. RESULTS: No significant differences were detected between the NK(1) receptor antagonist and control treatments with regard to peak vertical force, vertical impulse area, or subjective evaluations of lameness during standing, walking, or trotting, except during walking 24 hours after monosodium urate injection. CONCLUSIONS AND CLINICAL RELEVANCE: Preemptive administration of an NK(1) receptor antagonist failed to significantly improve subjective or objective outcome measures in dogs with monosodium urate-induced synovitis.     

In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

Effects of deracoxib or buffered aspirin on the gastric mucosa of healthy dogs

BACKGROUND: Use of cyclo-oxygenase-2 specific nonsteroidal anti-inflammatory drugs such as deracoxib has been advocated because of their anti-inflammatory actions and apparently low incidence of gastrointestinal adverse effects. HYPOTHESIS: Deracoxib will cause less endoscopically detectable gastric injury in dogs than aspirin, a nonselective nonsteroidal anti-inflammatory drug. ANIMALS: Twenty-four random source healthy dogs. METHODS: A randomized, placebo-controlled trial compared gastroscopic findings of dogs receiving placebo (q8h), aspirin (25 mg/kg PO q8h), or deracoxib (1.5 mg/kg QD, placebo ql2h) for 28 days. Gastroscopy on days -7, 6, 14, and 28 evaluated 4 regions of the stomach separately and visible lesions were scored. Dogs were observed every 8 hours for vomiting and diarrhea. Median total scores for each group were compared each day of endoscopic examination and total dog-days of vomiting and diarrhea were compared. Significance was determined at P < .05. RESULTS: There were significant differences in total scores of the aspirin group and both the placebo and deracoxib groups on days 6, 14, and 28. No significant differences in total scores were found between placebo and deracoxib on days 6, 14, and 28. Significant differences in dog-days of vomiting were found between the aspirin and deracoxib groups whereas no significant differences were found between the deracoxib and placebo groups. There was no detectable effect of treatment on dog-days of diarrhea. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of deracoxib to healthy dogs resulted in significantly lower gastric lesion scores, and fewer days of vomiting compared to aspirin, indicating that deracoxib is better tolerated than aspirin in some dogs.     

Effects of postoperative rehabilitation on limb function after cranial cruciate ligament repair in dogs

OBJECTIVE: To determine the effects of early postoperative rehabilitation on limb function in dogs after surgery for ruptured cranial cruciate ligament (RCCL). DESIGN: Prospective clinical study. ANIMALS: 51 client-owned dogs. PROCEDURE: Dogs weighing between 20 and 40 kg (44 to 88 lb) that had RCCL and medial meniscal injury were studied. After removal of the RCCL and complete medial meniscectomy, the stifle joint was stabilized by use of a lateral retinacular stabilization technique. Twenty-five dogs were included in a postoperative rehabilitation group, and 26 dogs were included in an exercise-restricted group. Limb function (peak vertical force [PVF] and vertical impulse [VI]) was determined before surgery and 6 months after surgery, using force platform gait analysis. RESULTS: Prior to surgery, mean PVF and VI in affected limbs were similar between groups. Six months after surgery, PVF and VI were significantly increased in dogs of both groups. However, PVF and VI in dogs in the rehabilitation group were significantly greater than those of dogs in the exercise-restricted group. At this time, differences in limb function (as measured by PVF and VI) between the repaired and normal limbs were not evident in dogs in the rehabilitation group. Conversely, limb function in the repaired limb of dogs in the exercise-restricted group was still significantly less than that of the normal limb. CONCLUSION AND CLINICAL RELEVANCE: Dogs that have surgery for RCCL and a torn medial meniscus benefit from postoperative rehabilitation; rehabilitation should be considered part of the postoperative management of these patients.     

Comparison of Intra-articular and Epidural Morphine for Analgesia Following Stifle Arthrotomy in Dogs

We prospectively studied 18 dogs that presented for exploratory stifle arthrotomy, with or without meniscectomy, and lateral extracapsular stabilization as a result of cranial cruciate ligament rupture. Dogs were premedicated with acepromazine, induced with thiopental, and maintained with halothane in oxygen. Preoperatively, dogs were assigned to one of three groups. Group 1 (n = 6) received intra-articular morphine (0.1 mg/kg diluted in 1 mL/10 kg body weight of saline) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 2 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural saline (1 mL/5 kg body weight saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 3 (n = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the volume of saline representing 0.1 mg/kg of morphine) and epidural morphine (0.1 mg/kg of morphine diluted in 1 mL/5 kg body weight saline). The efficacy of each analgesia regimen was evaluated for 6 hours postoperatively with a pain score based on subjective and objective variables. Serum Cortisol and blood glucose concentrations were measured. Butorphanol was used to provide analgesia as needed based on a predetermined maximum pain score. Supplemental analgesics were required postoperatively every 2 to 3 hours for 6 hours in all dogs that did not initially receive analgesics (group 2). Pain scores were significantly lower in dogs administered morphine intra-articularly (group 1) and epidurally (group 3) at 30 minutes and 30, 120, and 360 minutes, respectively, compared with dogs that did not initially receive analgesics (group 2). One dog in group 1 and one dog in group 3 required supplemental analgesia with butorphanol. There was no difference between analgesia produced by intra-articular morphine compared with that of epidural morphine. Side effects after intra-articular or epidural morphine were not observed. Intra-articular administration of morphine can produce effective analgesia in dogs comparable with that produced by epidural administration of morphine.     

Comparison of opioid and alpha-2 adrenergic receptor location and density in the horse and dog using radioligand binding

Ketamine, a noncompetitive NMDA receptor antagonist, has been shown to provide analgesia in some species. To target the NMDA receptor specifically and to potentially minimize some untoward side-effects, ketamine had been used epidurally. The objective of this study was to determine the analgesic effect of epidurally administered ketamine in dogs with chemically induced synovitis.
Sixteen healthy dogs were used. Dogs were anesthetized with propofol (4 mg kg⁻¹ IV). Synovitis was induced by injecting 1 mL of sodium urate crystal solution (10 mg mL⁻¹) into the right stifle. Dogs were allowed to recover and the synovitis was allowed to develop for 12 hours. The dogs were then anesthetized again using propofol (4 mg kg⁻¹ IV). Lumbosacral epidural injections were performed with each dog receiving either 2 mg kg⁻¹ of ketamine (20 mg mL⁻¹) or an equal volume of placebo (sterile water containing not more than 0.1 mg mL⁻¹ benzethonium chloride). Analgesia was assessed at baseline and then at 12, 14, 16, 18, 20, and 24 hours after induction of synovitis. Ground reaction forces (peak vertical force and impulse area) and overall pain were measured using a force platform and a pain scoring system (numerical rating scale).
Analysis of the data by Repeated Measures anova showed that the dogs developed a significant lameness between the baseline and 12 hours. However, no significant difference in ground reaction forces or total pain score was demonstrated between the treatment and control groups at any other time.
In conclusion, ketamine administered epidurally at a dose of 2 mg kg⁻¹ did not provide significant analgesia in dogs with chemically induced synovitis.     

Evaluation of the dose–response relationship of oral robenacoxib in urate crystal‐induced acute stifle synovitis in dogs

The objective of the study was to establish the dose–response relationship for robenacoxib, a selective cyclooxygenase (COX)‐2 inhibitor, in a urate crystal model of acute synovitis. In a randomized partial Latin square design trial, 12 beagle dogs were administered orally single doses of robenacoxib (0.5, 1, 2, 4 and 8 mg/kg), placebo and the positive control meloxicam (0.1 mg/kg), 3 h after injection of sodium urate crystals into a stifle joint. Dogs were assessed for weight bearing on a force plate and by subjective clinical orthopaedic observations. Robenacoxib produced dose‐dependent improvement in weight bearing, and decreased pain on palpation and joint swelling, over the dose range 0.5–2 mg/kg with no further increase in effect over the range 2–8 mg/kg. For weight bearing on the force plate, the ED₅₀ of robenacoxib was 0.6–0.8 mg/kg. The onset of action and time to peak effect of robenacoxib were faster (respectively, 2–2.5 h and 3–5 h) than for meloxicam (respectively, 3 h and 6 h). Robenacoxib significantly inhibited COX‐2 at all doses, with dose‐related activity. Robenacoxib did not inhibit COX‐1 over the dose range 0.5–4 mg/kg, but produced transient inhibition at 8 mg/kg. In conclusion, oral administration of robenacoxib over the dose range 0.5–8 mg/kg demonstrated significant analgesic and anti‐inflammatory efficacy in dogs.     

Reduced dosage of ketoprofen for the short-term and long-term treatment of joint pain in dogs

Two studies were conducted under laboratory conditions with 16 dogs to investigate the analgesic effectiveness of a low dose of ketoprofen in a short-term sodium urate crystal-induced synovitis model of arthritis. The effect of the treatment, defined as the improvement in peak vertical force weight bearing was evaluated in the first study at three dose levels. A single oral dose of 0.25 mg/kg ketoprofen was significantly better (P < 0.01) than the control (0 mg), but doses of 0.5 and 0.75 mg/kg did not improve the dogs' weight bearing further. The second study investigated the efficacy and safety of the 0.25 mg/kg dose administered daily for 30 days. The beneficial effects of ketoprofen at this dose were constant, with the treated dogs bearing 89.1 per cent of the baseline vertical force four hours after the induction of arthritis on day 1 and 92.2 per cent on day 29, compared with 42 per cent and 34 per cent of the baseline in the untreated dogs. No gastrointestinal or other side effects were observed during the treatment.     

In vivo comparison of two hinged transarticular external skeletal fixators for multiple ligamentous injuries of the canine stifle.

Controlled mobilization after the surgical repair of multiple disrupted ligaments is considered to be essential for return to normal function. This study compared the outcome after post-surgical mobilization without any protection to mobilization with two transarticular external skeletal fixator hinge prototypes after surgical repair of experimental injuries to multiple stifle ligaments in 15 hounds. The repair was left unprotected (NP: n=5), protected with a self-centering hinge (SH: n=5) and with a conventional hinge (CH: n=5) for four weeks after surgical repair. Outcome measurements included: orthopaedic examination, goniometric and thigh circumference (TC) measurements, total tibial translation (TT), radiographs, and kinetic gait analysis up to 120 days post-operatively. A significant effect of treatment controlling for time for medial collateral stability, TC, TT, osteophyte scores, peak vertical force (PVF) and vertical impulse (VI) was not found. There was a significant difference between time points for subjective lameness scores, TC, PVF, VI, TT and osteophyte scores within treatment. Stifle extension was significantly decreased in CH dogs compared to NP dogs on day 28. Stifle flexion was significantly decreased in CH and SH dogs on day 28 compared to NP dogs. Stifle flexion was normal in all dogs by day 42. Both hinges compromised stifle flexion initially after hinge removal, but range of motion normalized within two weeks. Hinges were not indicated for adjunct treatment after repair of multiple experimentally induced ligamentous stifle injuries.     

Analgesic and anti‐inflammatory actions of robenacoxib in acute joint inflammation in dog

Schmid, V. B., Spreng, D. E., Seewald, W., Jung, M., Lees, P., King, J. N. Analgesic and anti‐inflammatory actions of robenacoxib in acute joint inflammation in dog. J. vet. Pharmacol. Therap. 33 , 118–131. The objectives of this study were to establish dose–response and blood concentration–response relationships for robenacoxib, a novel nonsteroidal anti‐inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)‐2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra‐articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX‐1 and COX‐2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose‐related improvement in weight‐bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED₅₀ was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti‐inflammatory effects of robenacoxib were significantly superior to placebo (0.25–4 mg/kg robenacoxib) and were non‐inferior to meloxicam (0.5–4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose‐related inhibition of COX‐2 (estimated ED₅₀ was 0.52 mg/kg) but no inhibition of COX‐1. At a dosage of 1–2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.     

Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3'-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

OBJECTIVE: To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. ANIMALS: 24 dogs. PROCEDURE: Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. RESULTS: Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.     

Safety and tolerability of 3-week and 6-month dosing of Deramaxx® (Deracoxib) chewable tablets in dogs

Although non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing pain and inflammation, these agents have adverse effects. Selective inhibitors of COX-2 are an alternative to traditional NSAIDs. Deramaxx^® [Novartis Animal Health US, Inc. (NAH), Greensboro, NC, USA] contains the selective COX-2 inhibitor, deracoxib, and is approved for the relief of pain and inflammation associated with orthopedic surgery and osteoarthritis in dogs. The safety of Deramaxx was evaluated in two target animal safety studies: 40 dogs (four dogs/sex/group) received 0, 4, 6, 8, or 10 mg/kg/day deracoxib once daily for 21 days; and 60 dogs (five dogs/sex/group) received 0, 2, 4, 6, 8, or 10 mg/kg/day deracoxib once daily for 6 months. There was a dose-dependent trend towards increased blood urea nitrogen (BUN) in treated dogs, however mean BUN values remained within the reference range at the labeled doses. In both trials, histopathology revealed focal renal tubular degeneration/regeneration in some dogs receiving ≥6 mg/kg/day deracoxib. Focal renal papillary necrosis was seen in one dog treated with 8 mg/kg/day and in three dogs receiving 10 mg/kg/day deracoxib on the 6-month study. No other parameters of renal function were adversely affected for either study. Results show that Deramaxx is safe and well-tolerated in dogs when administered as directed.     

Evaluation of S-adenosyl l-methionine in a double-blinded, randomized, placebo-controlled, clinical trial for treatment of presumptive osteoarthritis in the dog

Objective: To evaluate the efficacy of S‐adenosyl l ‐methionine (SAMe) in the treatment of clinically inferred canine osteoarthritis (OA). Study Design: Six weeks, double‐blinded, placebo‐controlled, clinical trial. Animals: Dogs (n=33) with clinical signs, history, and orthopedic exams consistent with OA. Methods: Dogs were block randomized by body condition score (<6/9, or ≥6/9) into either the placebo or SAMe group. Outcome was assessed using pressure platform gait analysis, examination score, goniometry, and the Canine Brief Pain Inventory (CBPI) at the time of study entrance and at 3 and 6 weeks after entry. Groups were compared using parametric and nonparametric paired tests as appropriate, and numbers needed to treat (NNT) were calculated for the CBPI and peak vertical force (PVF). Results: Both groups (n=15 placebo, n=18 SAMe) had a reduction in mean PVF (P=.02) and vertical impulse (VI; P=.06) from the 1st to 3rd visit. There was no significant difference between the placebo group and SAMe group for PVF, VI, or either part of the CBPI (Severity or Impact). The NNT at 6 weeks for the Severity score was 3, Impact score was 25, and PVF was 45. Conclusions: These data do not support the use of SAMe as an effective stand alone treatment for reducing clinical signs of OA, as measured by PVF, VI, goniometry, CBPI (both Severity and Impact), and examination score within 6 weeks of treatment.     

The clinical, cerebrospinal fluid, and histopathologic effects of epidural ketorolac in dogs

OBJECTIVE: To evaluate the clinical, cerebrospinal fluid (CSF), and histopathologic effects of epidural ketorolac. STUDY DESIGN: Blinded, randomized, placebo controlled study. ANIMALS: Twenty-two adult mixed breed dogs with 16 treatment and 6 control dogs, weighing 14.4 to 29.8 kg. METHODS: Dogs were anesthetized and epidural catheters were placed at the lumbosacral space. Catheter placement was evaluated fluoroscopically. Ketorolac (0.4 mg/kg) or placebo (5% ethanol) was administered epidurally over a 52-hour period, with 5 injections given at 12-hour intervals. At 1, 2, 4, or 8 hours after the first and last injection of ketorolac, dogs were anesthetized and CSF was obtained. Control dogs had CSF sampled 1 hour after the first and last ethanol injection. Neurologic function and pain responses were evaluated before and during the study. Selected dogs were then killed and necropsies performed. RESULTS: None of the dogs exhibited any clinical or neurologic abnormalities during the study. No statistical difference was noted in pain response or CSF analysis between treatment and control dogs. Gross necropsy revealed gastrointestinal ulceration of varying degrees in all treatment dogs. Histopathologic analysis of the spinal cord and meninges revealed minimal focal leptomeningeal phlebitis in 2 of 8 treatment dogs and minor subdural inflammation in 1 control dog. No changes to the neural structures were noted in any dogs. CONCLUSIONS: Epidural administration of ketorolac did not cause clinical signs, alteration in CSF values, or pathologic changes to the spinal cord when used for short duration. Gastrointestinal ulceration was common when ketorolac was administered epidurally at 0.4 mg/kg every 12 hours for 5 treatments. CLINICAL RELEVANCE: This study documented the neurologic safety of epidural ketorolac in dogs before an efficacy trial can be performed. Gastrointestinal ulceration may limit use to short duration or a single injection.     

Firocoxib efficacy preventing urate-induced synovitis, pain, and inflammation in dogs

This positive-control study evaluated the efficacy of firocoxib versus carprofen, deracoxib, and meloxicam for the prevention of pain and inflammation in a urate crystal synovitis model of lameness. Lameness scoring and force plate gait analysis were used to assess efficacy. The resulting lameness scores and force plate ground reaction forces after urate crystal injection were not significantly different among the groups. Relative to each group's baseline (nonlame) score, only the firocoxib group was not significantly lame, based on lameness score, at the model's peak effect.     

Comparison of Force Plate Gait Analysis and Owner Assessment of Pain Using the Canine Brief Pain Inventory in Dogs with Osteoarthritis

Background

Lameness assessment using force plate gait analysis (FPGA) and owner assessment of chronic pain using the Canine Brief Pain Inventory (CBPI) are valid and reliable methods of evaluating canine osteoarthritis. There are no studies comparing these 2 outcome measures.

Objective

Evaluate the relationship between CBPI pain severity (PS) and interference (PI) scores with the vertical forces of FPGA as efficacy measures in canine osteoarthritis.

Animals

Sixty‐eight client‐owned dogs with osteoarthritis (50 hind limb and 18 forelimb).

Methods

Double‐blind, randomized. Owners completed the CBPI, and dogs underwent FPGA on days 0 and 14. Dogs received carprofen or placebo on days 1 through 14. The change in PS and PI scores from day 0 to 14 were compared to the change in peak vertical force (PVF) and vertical impulse (VI).

Results

PS and PI scores significantly decreased in carprofen‐ compared with placebo‐treated dogs (P = .002 and P = .03, respectively). PVF and VI significantly increased in carprofen‐ compared with placebo‐treated dogs (P = .006 and P = .02, respectively). There was no correlation or concordance between the PS or PI score changes and change in PVF or VI.

Conclusions and Clinical Importance

In these dogs with hind limb or forelimb osteoarthritis, owner assessment of chronic pain using the CBPI and assessment of lameness using FPGA detected significant improvement in dogs treated with carprofen. The lack of correlation or concordance between the change in owner scores and vertical forces suggests that owners were focused on behaviors other than lameness when making efficacy evaluations in their dogs.