Validation of a structured questionnaire as an instrument to measure chronic pain in dogs on the basis of effects on health-related quality of life

OBJECTIVE: To validate the use of a novel questionnaire as an instrument for measurement of chronic pain in dogs through its impact on health-related quality of life (HRQL). ANIMALS: 108 dogs with chronic degenerative joint disease and 26 healthy dogs. PROCEDURES: Questionnaire responses were subjected to factor analysis (FA) and questionnaire scores to discriminant analysis to evaluate construct validity. Questionnaire scores were used to explore the potential of this instrument for minimizing respondent bias and for evaluative purposes. RESULTS: FA results revealed a sensible factor structure accounting for 65% of the variance in data, with factors identifiable as domains of HRQL in dogs affected by chronic pain. Further evidence for construct validity was provided when questionnaire scores were used to discriminate, on the basis of 218 questionnaires, between dogs with clinician-awarded pain scores of 0 and dogs with pain scores >or= 1 (88% discrimination, with 95% of no-pain group dogs and 87% of some-pain group dogs correctly categorized). Use of the questionnaire provided minimized respondent bias. CONCLUSIONS AND CLINICAL RELEVANCE: Validation of the questionnaire as an instrument for discriminative and evaluative measurements of orthopedic chronic pain through its impact on HRQL in dogs was provided. Use of the questionnaire, with further testing and refinement, may support improved clinical decision making, facilitate development of evidence-based therapeutic options for chronic diseases, and help veterinarians and owners define humane end points in dogs. IMPACT FOR HUMAN MEDICINE: Information gained here may provide improved measurements of clinical change in animal studies that use dogs with naturally occurring chronic pain to evaluate novel human treatment protocols.     

Development of a behaviour-based scale to measure acute pain in dogs

A composite scale for assessing pain in dogs in a hospital setting has been developed on the basis of observations of their behaviour. Initially, 279 words and expressions suggested by 69 veterinary surgeons were reduced into 47 words and expressions which were allocated into seven behaviour categories: demeanour and response to people, posture, mobility, activity, response to touch, attention to painful area and vocalisation. Three statistical methods, hierarchical agglomerative cluster analysis, Cronbach's alpha coefficient, and analysis of variance with multiple comparisons and empirical cumulative distributions, were used to validate these procedures, and a questionnaire accompanied by a list of definitions was designed around the expressions. The new composite scale is more detailed than previously reported scales for assessing pain in dogs on the basis of their behaviour, and the methods used in its development are based on sound scientific principles.     

Clinical efficacy and tolerance of meloxicam in dogs with chronic osteoarthritis

A clinical trial was conducted to evaluate the safety and efficacy of the nonsteroidal anti-inflammatory drug meloxicam in dogs with chronic osteoarthritis. Forty clinical cases were enrolled in the 2-phase study. Phase 1 compared therapeutic efficacy and tolerance of meloxicam or placebo for 1 week. Phase 2 involved a 4-week evaluation of the drug's clinical efficacy and tolerance. Clinical efficacy was evaluated by using a scoring system that assessed specific lameness, general stiffness, painful rise, exercise intolerance, and behavior. Evaluations demonstrated significant reductions (P < 0.05) in clinical signs of osteoarthritis following 4 weeks of drug therapy. Side effects were minimal in extent and duration. The drug was accepted without problems in the majority of cases. The findings of this investigation suggest that the efficacy, tolerance, and formulation of meloxicam oral suspension make it well suited for the treatment of chronic osteoarthritis in the dog.     

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.     

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.     

Development of a scale to evaluate postoperative pain in dogs

OBJECTIVE: To design and evaluate a scale for measurement of postoperative pain in dogs. DESIGN: Randomized, blinded, prospective study, with positive- and negative-control groups. ANIMALS: 36 dogs undergoing general anesthesia for ovariohysterectomy and 12 dogs undergoing general anesthesia without surgery. PROCEDURE: A pain assessment scale was developed for dogs, which incorporated physiologic data (heart and respiratory rates) and behavioral responses (response to palpation, activity, mental status, posture, and vocalization). This pain scale was then applied to a study in which dogs were allocated to 2 groups, depending on the type of medication administered (acepromazine maleate only or acepromazine and butorphanol) before induction of general anesthesia. The 36 dogs that had ovariohysterectomy were allocated to 3 groups, members of which received butorphanol, carprofen, or no analgesic after surgery. Dogs were scored for signs of pain and videotaped at 0, 1, 2, 4, 6, 8, 12, and 18 hours after surgery by an assessor who was blinded to the groups. Results were analyzed for significant differences in pain scores for single categories and total pain scores among groups. Video segments were scrambled and then scored by a second external assessor to test the repeatability of the results, using the pain assessment scale. RESULTS: Mean total pain scores were significantly different between the group of dogs that underwent general anesthesia only and each group of dogs that underwent general anesthesia and surgery. Pain scores for the analgesic-treatment groups reflected the known onset and duration of action of the analgesic used. Agreement between the internal and external assessors was excellent and indicated high precision between the 2 assessors for the population of dogs as a whole. CLINICAL IMPLICATIONS: Behavioral and physiologic measurements can be used reliably to evaluate degree of pain in dogs during the postoperative period and their response to analgesics.     

Evaluation of resting cortisol concentration testing in dogs with chronic gastrointestinal signs

BackgroundResting cortisol concentrations are routinely measured in dogs with chronic gastrointestinal signs to rule out hypoadrenocorticism based on a concentration >2 μg/dL (>55 nmol/L).Hypothesis/ObjectivesTo assess the cross‐sectional prevalence of hypoadrenocorticism in a group of dogs with chronic gastrointestinal signs presented to a referral internal medicine service.AnimalsTwo‐hundred and eighty‐two client‐owned dogs with chronic gastrointestinal signs and with resting cortisol concentration testing performed.MethodsRetrospective review of medical records (final diagnosis, resting cortisol concentration, and adenocorticotropic hormone [ACTH] stimulation test results) of a referral population of dogs between May 2013 and September 2017.ResultsResting cortisol concentration was <2 μg/dL (<55 nmol/L) in 79 patients (28%). Repeated resting cortisol concentration measurements were performed in 28 dogs, and in 8, resting cortisol concentrations remained <2 μg/dL (<55 nmol/L). Post‐ACTH cortisol concentration was <2 μg/dL (<55 nmol/L) in 1 dog, consistent with a diagnosis of hypoadrenocorticism and giving a prevalence estimate of hypoadrenocorticism in this population of dogs of 0.3% (95% confidence interval [95CI], 0.03‐1.5%). In 19 dogs with an initial resting cortisol concentration <2 μg/dL (<55 nmol/L), hypoadrenocorticism was excluded based on a repeat resting cortisol concentration >2 μg/dL (>55 nmol/L). Overall, the most common diagnosis was chronic primary inflammatory enteropathy (176/282, 62.4%), followed by extragastrointestinal neoplasia (17/282, 6%), protein‐losing enteropathy, pancreatitis and megaesophagus (10/282, 3.5% each).Conclusions and Clinical ImportanceAlthough dogs with hypoadrenocorticism can present with chronic gastrointestinal signs, it was the final diagnosis in only 1 of 282 dogs presenting to a referral internal medicine service for signs of chronic enteropathy. Repeated resting cortisol concentration may be considered as a test to try and exclude hypoadrenocorticism.     

The effect of carprofen on selected markers of bone metabolism in dogs with chronic osteoarthritis

The purpose of this study was to investigate the effect of the nonsteroidal anti-inflammatory drug carprofen on bone turnover and to monitor the progress of chronic osteoarthritic dogs by measuring different bone markers and radiographic evalutation of the corresponding joints. For this purpose 20 dogs of different ages and weight were devided into 2 groups. Ten dogs were assigned to Group R, treated with carprofen, and ten dogs to Group C, which had no treatment. Radiographs of the affected joints were reviewed initially and six months later at the end of the experiment. Blood was taken 8 times from each dog. Four bone markers (Osteocalcin (OC), bone-specific alkaline phosphatase (bAP), carboxyterminal telopeptide of type I collagen (ICTP), serum CrossLaps (CTX) as well as 1,25-(OH)2-Vitamin D and parathyroid hormone (PTH) were monitored for 6 months. No significant group effects on bone markers were notied. In Group R a decrease in ICTP concentrations during the first three months and a significant decrease in CTX concentrations in the first two months of the study were observed. The bone formation marker bAP revealed a significant decrease throughout the experiment. Three dogs of Group C and one dog of Group R showed osteoarthritic progression in the radiographs. The significant decrease of CTX indicates that carprofentreatment could have a retarding effect on the progression of osteoarthritis. Radiological findings suggest that carprofen may delay osteophyte formation. The monitoring of focal metabolic processes as in bone of a osteoarthrotic joint is difficult, since the bone mass is very active and metabolic processes may have an influence on the monitoring.     

In vivo effects of tepoxalin, an inhibitor of cyclooxygenase and lipoxygenase, on prostanoid and leukotriene production in dogs with chronic osteoarthritis

OBJECTIVE: To evaluate in vivo effects of tepoxalin, an inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), on prostaglandin (PG) and leukotriene production in osteoarthritic dogs. ANIMALS: 7 mixed-breed adult dogs with chronic unilateral arthritis of a stifle joint. PROCEDURE: Dogs were treated in accordance with a randomized 3-way crossover design. Each dog received an inert substance, meloxicam, or tepoxalin for 10 days. On day 0 (baseline), 3, and 10, dogs were anesthetized and samples of blood, stifle joint synovial fluid, and gastric mucosa were collected. Concentrations of PGE2 were measured in synovial fluid and after lipopolysaccharide stimulation of whole blood; PGE1 and PGE2 synthesis was measured in gastric mucosa.Thromboxane B2 (TxB2) concentration was measured in whole blood. Leukotriene B4 (LTB4) concentration was determined in gastric mucosa and in whole blood after ex vivo stimulation with a calcium ionophore. RESULTS: Tepoxalin significantly decreased LTB4 concentrations in the blood and gastric mucosa at day 10 and TxB2 concentrations in the blood and PGE2 in the gastric mucosa and synovial fluid at days 3 and 10, compared with baseline values. Meloxicam significantly decreased PGE2 concentrations in the blood at days 3 and 10 and synovial fluid at day 3. Meloxicam also decreased PGE1 and PGE2 synthesis in the gastric mucosa at day 3. Meloxicam did not affect LTB4 synthesis in the blood or LTB4 concentrations in the gastric mucosa. CONCLUSIONS AND CLINICAL RELEVANCE: Tepoxalin has in vivo inhibitory activity against COX-1, COX-2, and 5-LOX in dogs at the current approved recommended dosage.     

Therapeutic options for the treatment of chronic pain in dogs

Chronic pain is a widely recognised problem in humans and is being increasingly recognised as a significant problem in dogs. Whilst a large number of therapies are described and utilised to treat chronic pain in dogs, there is a severe shortage of evidence to guide practitioners in selection of treatments. Until more evidence becomes available, practitioners should adopt a cautious approach, utilising licensed treatments first when possible. Non‐pharmacological therapies should be incorporated into the chronic pain management plan whenever possible. Given the probable prevalence of chronic pain in dogs there is an urgent need for research to identify effective treatments.     

Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not always provide sufficient pain relief in dogs with osteoarthritis (OA). HYPOTHESIS: The use of amantadine in addition to NSAID therapy will provide improved pain relief when compared with the use of nonsteroidal analgesics alone in naturally occurring OA in dogs. ANIMALS: Thirty-one client-owned dogs with pelvic limb lameness despite the administration of an NSAID. METHODS: The study was randomized, blinded, and placebo controlled with parallel groups (days 21-42). On day 0, analgesic medications were discontinued. On day 7, all dogs received meloxicam for 5 weeks. On day 21, all dogs received amantadine (3-5 mg/kg once daily per os) or placebo for 21 days, in addition to receiving meloxicam. Assessments were performed before the study and on days 7, 21, and 42. Primary outcome measures were blinded owner assessments of activity using client-specific outcome measures (CSOM) on days 0, 7, 21, and 42. Data were analyzed by a mixed model approach. RESULTS: For CSOM activity, there was a significant time by treatment effect (P=.009). On the basis of the planned post hoc t-tests of postrandomization means, there was a significant difference between treatment groups on day 42 (P=.030), with the amantadine group being more active. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with osteoarthritic pain refractory to an NSAID, physical activity is improved by the addition of amantadine. Amantadine might be a useful adjunct therapy for the clinical management of canine osteoarthritic pain.     

Efficacy of licofelone in dogs with clinical osteoarthritis

To evaluate the effect of licofelone, an arachidonic acid substrate with combined inhibitory activity against 5-lipoxygenase and cyclooxygenases 1 and 2, a double-blind, randomised and placebo-controlled study was conducted in 33 client-owned dogs that were lame owing to hindlimb osteoarthritis. Seventeen of the dogs received a placebo and 16 were treated with 2.5 mg/kg licofelone twice a day for 28 days. The dogs' lameness was assessed on a visual analogue scale (vas), and by force plate analyses at baseline and 14 and 28 days after starting the treatment. After 14 days the mean (se) change in peak vertical force in the licofelone-treated dogs (1.7 [0.8] per cent bodyweight) was significantly greater (P<0.05) than in the placebo-treated dogs (-0.3 [0.6] per cent bodyweight), and after 28 days the difference had increased. In contrast, the dogs' lameness, as assessed by the vas values, had decreased significantly over baseline in both the treated and control groups.