Emily H. Griffith

Detection of Clinically Relevant Pain Relief in Cats with Degenerative Joint Disease Associated Pain

Background Detection of clinically relevant pain relief in cats with degenerative joint disease (DJD) is complicated by a lack of validated outcome measures and a placebo effect. Hypothesis/Objectives To evaluate a novel approach for detection of pain relief in cats with DJD. Animals Fifty‐eight client‐owned cats. Methods Prospective, double‐masked, placebo‐controlled, stratified, randomized, clinical study. Enrolled cats were 6–21 years of age, with owner‐observed mobility impairment, evidence of pain in at least 2 joints during orthopedic examination, and overlapping radiographic evidence of DJD, and underwent a 2‐week baseline period, 3‐week treatment period with placebo or meloxicam, and 3‐week masked washout period. Outcome measures were evaluated at days 0, 15, 36, and 57. Results Both groups significantly improved after the treatment period (day 36) on client‐specific outcome measures (CSOM) and feline musculoskeletal pain index (FMPI) (P < .0001 for both); there was no difference between the groups on CSOM or FMPI score improvement. After the masked washout period, more cats that received meloxicam during the treatment period had a clinically relevant decrease in CSOM score (P = .048) and FMPI score (P = .021) than cats that received placebo. Conclusions and Clinical Importance Using both a client‐specific and a general clinical metrology instrument, owners of cats with DJD were able to detect evident recurrence of clinical signs after withdrawal of active medication than after withdrawal of placebo, and that this study design might be a novel and useful way to circumvent the placebo effect and detect the efficacy of pain‐relieving medications.

Feasibility and repeatability of cold and mechanical quantitative sensory testing in normal dogs

Feasibility and inter-session repeatability of cold and mechanical quantitative sensory testing (QST) were assessed in 24 normal dogs. Cold thermal latencies were evaluated using a thermal probe (0°C) applied to three pelvic limb sites. Mechanical thresholds were measured using an electronic von Frey anesthesiometer (EVF) and a blunt-probed pressure algometer (PA) applied to the dorsal aspect of the metatarsus. All QST trials were performed with dogs in lateral recumbency. Collection of cold QST data was easy (feasible) in 19/24 (79%) dogs. However, only 18.4%, 18.9% and 13.2% of cold QST trials elicited a response at the medial tibia, third digital pad and plantar metatarsal regions, respectively. Collection of mechanical QST data was easy (feasible) in 20/24 (83%) dogs for both EVF and PA. At consecutive sampling times, approximately 2 weeks apart, the average EVF sensory thresholds were 414 ± 186 g and 379 ± 166 g, respectively, and the average PA sensory thresholds were 1089 ± 414 g and 1028 ± 331 g, respectively. There was no significant difference in inter-session or inter-limb threshold values for either mechanical QST device. The cold QST protocol in this study was achievable, but did not provide consistently quantifiable results. Both mechanical QST devices tested provided repeatable, reliable sensory threshold measurements in normal, client-owned dogs. These findings contribute to the validation of the EVF and PA as tools to obtain repeated QST data over time in dogs to assess somatosensory processing changes.

Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats.

Introduction Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM). Methods Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period. Results Activity counts were increased in cats during treatment with daily meloxicam (p<0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042). Conclusions Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease.

Gait scoring in dogs with thoracolumbar spinal cord injuries when walking on a treadmill

BackgroundAn inexpensive method of generating continuous data on hind limb function in dogs with spinal cord injury is needed to facilitate multicentre clinical trials. This study aimed to define normal fore limb, hind limb coordination in dogs walking on a treadmill and then to determine whether reliable data could be generated on the frequency of hind limb stepping and the frequency of coordinated stepping in dogs with a wide range of severities of thoracolumbar spinal cord injury.ResultsSixty-nine neurologically normal dogs of different body sizes including seven lame dogs were videotaped walking on the treadmill without prior training and all used the lateral gait of right fore, left hind, left fore, right hind (RF-LH-LF-RH). Severely paraparetic dogs were able to walk on the treadmill for a minimum of 75 seconds, scoring of which generated data representative of function in animals with extremely variable gaits. Fifty consecutive stepping cycles were scored by three observers in 18 dogs with a wide range of disability due to acute thoracolumbar spinal cord injury using a stepping score (hind limb steps/fore limb steps ×100), and a coordination score (coordinated hind limb steps/total hind limb steps ×100). Dogs were also scored using a previously validated ordinal open field score (OFS). Inter- and intraobserver agreement was high as assessed with Cronbach’s alpha test for internal reliability. The stepping and coordination scores were significantly correlated to each other and to the OFS.ConclusionsDogs with naturally occurring spinal cord injury can walk on a treadmill without prior training and their hind limb function can be scored reliably using a stepping score and coordination score. The only requirements for data acquisition are a treadmill and appropriately positioned video camera and so the system can be used in multicentre clinical trials to generate continuous data on neurologic recovery in dogs.

Feasibility and repeatability of thermal quantitative sensory testing in normal dogs and dogs with hind limb osteoarthritis-associated pain.

The objectives of this study were to determine whether thermal quantitative sensory testing (QST) can be performed in client-owned dogs, is repeatable and whether QST differs between normal dogs and dogs with hind limb osteoarthritis (OA). This clinical, prospective, observational study used clinically normal dogs (n=23) and dogs with OA-associated hind limb pain (n=9). Thermal QST was performed in standing dogs using a high-powered light source delivered by a previously validated system. Dogs were tested on two occasions, 2 weeks apart. Five tests were performed on each hind limb at each time point. Repeated measures analysis of variance was used to evaluate the effects of leg, time point and OA/normal status on thermal threshold latencies (TTL). Additionally, paired t tests were used to compare the TTL of left and right limbs within groups and between time points. Thermal thresholds were successfully measured in 32 client-owned dogs without prior training. TTL were significantly different between normal and OA dogs (P=0.012). There was no difference between limbs (P=0.744) or time periods (P=0.572), when analyzed by repeated measures analysis of variance, and no interactions between group and limb, visit and limb, or visit and group. In conclusion, thermal thresholds can be measured in client owned dogs with no prior training and are repeatable from week to week. Further data are required to determine if OA results in thermal hypoalgesia as measured at the distal hind limb and whether this is an indication of central sensitization.

Surgically planned versus histologically measured lateral tumor margins for resection of cutaneous and subcutaneous mast cell tumors in dogs: 46 cases (2010-2013).

OBJECTIVE To compare preplanned lateral surgical margins and measured lateral histologic margins for cutaneous and subcutaneous mast cell tumor (MCT) resections in dogs. DESIGN Retrospective case series. SAMPLE 51 biopsy specimens from dogs (n = 46) with MCTs. PROCEDURES All canine patients that underwent curative-intent surgical resection of cutaneous or subcutaneous MCTs from January 1, 2010, through June 30, 2013, with complete medical records including signalment, body condition score (BCS), surgery report (with measured surgical margins), and histopathology report were included. The surgically measured tumor margins in each quadrant were grouped and compared with the corresponding histologic margins. Specimens from dogs with truncal MCTs and a BCS of 7 to 9 on a scale from 1 to 9 (ie, high) were compared with those of dogs with a BCS of 4 to 6 to evaluate effect of BCS on tissue margins. RESULTS 51 specimens were included. Surgically mapped lateral margins differed significantly from histologically reported margins in all 4 quadrants. The mean histologic margins were 35% to 42% smaller than the surgical margins for the combined 51 specimens. A higher BCS did not significantly influence the magnitude of the decrease in lateral margins measured histologically. No significant difference was found for the magnitude of the differences between any of the 4 lateral margins. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that surgical and histologic margins may differ significantly for canine cutaneous and subcutaneous MCTs. This may be a result of tissue shrinkage following excision and fixation, extension of the MCT beyond palpable margins, or both. Histologic measurements may significantly underestimate the tumor-free margins in dogs with cutaneous and subcutaneous MCTs.

A Feline-Specific Anti-Nerve Growth Factor Antibody Improves Mobility in Cats with Degenerative Joint Disease-Associated Pain: A Pilot Proof of Concept Study.

Background Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans. Objectives To evaluate the efficacy of a fully felinized anti‐NGF antibody (NV‐02) for the treatment of DJD pain and mobility impairment in cats. Animals Thirty‐four client‐owned cats with DJD‐associated pain and mobility impairment. Methods In a placebo‐controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV‐02 (0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Additionally, owners completed clinical metrology instruments (client‐specific outcome measures [CSOM] and feline musculoskeletal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated‐measures model was used to evaluate the objective activity data. Results NV‐02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4 (P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a significant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified the treatment administered compared with 45% of owners in the placebo group (P = .013). No treatment‐related adverse effects were identified. Conclusions These pilot data demonstrate a 6‐week duration positive analgesic effect of this fully felinized anti‐NGF antibody in cats suffering from DJD‐associated pain.

Use of oral trazodone for sedation in cats: a pilot study

Objectives Resistance to transportation and stressful veterinary visits are major causes for a decrease in feline veterinary care. Few options exist for oral sedatives to reduce cats’ anxiety prior to veterinary visits. The purpose of this study was to evaluate the safety and efficacy of oral trazodone for use as a single dose agent for sedation in cats. Methods Six laboratory cats were given single 50, 75 and 100 mg doses of trazodone and placebo. Trazodone 100 mg and placebo treatments were randomized. Pre- and post-study laboratory values and physical examinations were compared. During each 4 h period post-treatment, sedation was measured via accelerometers and video observations scored by an observer blinded to treatment. Examinations were performed on the cats 90 mins after treatment, and their behavioral responses scored by the same blinded observer. Results No adverse effects or changes in physical examinations or laboratory values were detected as a result of trazodone administration. Accelerometer data showed trazodone 50, 75 and 100 mg caused sedation as measured by activity reduction (83%, 46% and 66%, respectively). In contrast, there was a 14% activity increase after placebo. There was a significant reduction in video observation scores when cats were given trazodone 100 mg compared with placebo. Mean latency to peak sedation for trazodone 100 mg occurred at 2 h. Scores for behavioral response to examination, performed at 90 mins post-treatment, were not significantly different between cats receiving trazodone 100 mg and placebo. Conclusions and relevance Trazodone was well tolerated in this population of cats and caused appreciable sedation at all doses. Behavior during examination was not significantly different when cats received trazodone 100 mg compared with placebo. Further studies are recommended to investigate the use of oral trazodone in cats for the purpose of decreasing anxiety assocaited with transportation and examination.

Medullary Position at the Craniocervical Junction in Mature Cavalier King Charles Spaniels: Relationship with Neurologic Signs and Syringomyelia

Background Medullary elevation (ie, medullary kinking) at the craniocervical junction (CCJ) is reported in dogs with Chiari‐like malformations (CM), but its diagnostic criteria and clinical relevance are unclear. Objective To describe the position of the medulla at the CCJ in mature cavalier King Charles spaniels (CKCS), and evaluate its relationship with clinical status and the presence of syringomyelia. Animals Thirty‐six CKCS, 5–12 years of age, including 16 asymptomatic dogs. Methods Dogs were assigned a neurologic grade; magnetic resonance imaging (MRI) of the CCJ then was performed. The presence of a CM and syringomyelia was recorded and syringomyelia severity was quantified. Medullary position was quantified using the medullary kinking index, the elevation angle and obex position relative to the foramen magnum. The relationship between medullary position measures and presence and severity of neurologic signs and syringomyelia was investigated. Results Chiari‐like malformation was found in 33 dogs; 26 of them had syringomyelia. Mean medullary kinking index was 46.4% (SD, 10.3), elevation angle was 132° (SD, 12) and obex position was 3.5 mm (SD, 0.8). A higher medullary kinking index was associated with the presence of neurologic signs (P = .0368). Obex position was associated with the presence (P = .0018) and severity of syringomyelia (P = .0164). Conclusions and clinical importance There is a significant association between medullary elevation and clinical signs, whereas more caudal brainstem positions appear related to the presence of syringomyelia.

Dorsal Compressive Atlantoaxial Bands and the Craniocervical Junction Syndrome: Association with Clinical Signs and Syringomyelia in Mature Cavalier King Charles Spaniels

Background Dorsal compressive lesions at the atlantoaxial junction (ie, AA bands) occur in dogs with Chiari‐like malformations (CMs), but their clinical relevance is unclear. Objective Investigate the influence of AA bands on clinical status and syringomyelia (SM) in mature cavalier King Charles spaniels (CKCS). Animals Thirty‐six CKCS, 5–12 years of age, including 20 dogs with neuropathic pain. Methods Dogs were examined and assigned a neurologic grade. Magnetic resonance imaging (MRI) of the craniocervical junction was performed with the craniocervical junction extended and flexed (ie, normal standing position). Imaging studies were assessed for the presence of an AA band, CM, SM or some combination of these findings. Band and SM severity were quantified using an objective compression index and ordinal grading scale, respectively. Results Of 36 CKCS imaged, 34 had CM. Atlantoaxial bands were present in 31 dogs and were more prominent in extended than flexed positions. Syringomyelia was found in 26 dogs, 23 of which also had AA bands. Bands were associated with both the presence (P = .0031) and severity (P = .008) of clinical signs and SM (P = .0147, P = .0311, respectively). Higher compression indices were associated with more severe SM (P = .0137). Conclusions Prevalence of AA bands in older CKCS is high. Positioning of dogs in extension during MRI enhances the sensitivity of the study for detecting this important abnormality. There were significant associations among AA bands, clinical signs, and SM in dogs with CM; additional work is needed to understand whether or not this relationship is causal.