The present and future of opioid analgesics in small animal practice.

Opioids are the cornerstone for the treatment of acute pain in small animal patients. This is primarily because of their remarkable safety profile, high efficacy, and benefit of reversibility. There have been some significant advances in our knowledge on opioid pharmacology and clinical usage in companion animal medicine. This review discusses the progression of opioid use in small animal practice providing current misconceptions and controversies in light of routes of administration. Potential targets for research and drug development and novel therapies are discussed in addition to the concepts of glial cell modulators, individual variability, and opioid tolerance and hyperalgesia. The future brings an interesting perspective with the application of pharmacogenetics and individualized pain management in canine and feline practice.

Fully automated deep learning models with smartphone applicability for prediction of pain using the Feline Grimace Scale.

This study used deep neural networks and machine learning models to predict facial landmark positions and pain scores using the Feline Grimace Scale© (FGS). A total of 3447 face images of cats were annotated with 37 landmarks. Convolutional neural networks (CNN) were trained and selected according to size, prediction time, predictive performance (normalized root mean squared error, NRMSE) and suitability for smartphone technology. Geometric descriptors (n = 35) were computed. XGBoost models were trained and selected according to predictive performance (accuracy; mean square error, MSE). For prediction of facial landmarks, the best CNN model had NRMSE of 16.76% (ShuffleNetV2). For prediction of FGS scores, the best XGBoost model had accuracy of 95.5% and MSE of 0.0096. Models showed excellent predictive performance and accuracy to discriminate painful and non-painful cats. This technology can now be used for the development of an automated, smartphone application for acute pain assessment in cats.

Quality of amoxicillin/clavulanic acid oral formulations for intended veterinary use in the UK, Malaysia, Serbia and Thailand.

OBJECTIVES: Amoxicillin/clavulanate is the most commonly used oral antimicrobial drug in companion animals. The objective of the study was to detect types and frequency of deficits in the quality of veterinary oral formulations of amoxicillin/clavulanate in various countries. MATERIALS AND METHODS: In a prospective study with purposive sampling, amoxicillin/clavulanate tablet formulations for canine use were collected in four countries (wholesalers or veterinary practice) and shipped to a central bioanalytical laboratory. Twenty-four samples were collected from the UK (nine), Malaysia (nine), Serbia (four) and Thailand (two), yielding 18 different formulations (10 veterinary). Packaging inspection, tablet disintegration and content assay were conducted (validated high-performance liquid chromatography with ultra-violet detection); content was acceptable when within the 90% to 120% pre-specified range (US Pharmacopeia). RESULTS: Secondary packaging was present for 13 of 24 samples and primary packaging integrity was verified for all but one sample. Amoxicillin trihydrate/potassium clavulanate label ratio was 4:1, except for three formulations (2:1). Tablet dose strength ranged from 250 to 625 mg. All formulations contained both analytes. For amoxicillin, two of 24 samples were out of specification with 72.8% (Malaysia) and 82.3% (Thailand) of labelled content. For clavulanate, four of 24 samples were out of specification with 46.9% (Serbia), 79.0% (UK), 84.3% (Serbia) and 86.5% (Thailand) of labelled content. One formulation (Thailand) failed for both analytes. CLINICAL SIGNIFICANCE: Antimicrobial formulations of substandard quality have negative consequences for efficacy in patients and potentially promote antimicrobial resistance. There was evidence of substandard formulations in all countries, not only for amoxicillin but especially for clavulanate; this could compromise equitable access to acceptable quality essential veterinary medicines worldwide.

Ice therapy: cool, current and complicated.

This is the fourth Capsule review article provided by the WSAVA Global Pain Council and which discusses the use of ice or cold therapy as a non-pharmacologic modality for pain control in small animal practice. The physiological effects of cold therapy on tissues, receptors and ion channels are discussed; as well as indications, recommendations for, and limitations of use.

World Small Animal Veterinary Association Global Dental Guidelines.

Dental, oral, and maxillofacial diseases are some of the most common problems in small animal veterinary practice. These conditions create significant pain as well as localized and potentially systemic infection. As such, the World Small Animal Veterinary Association (WSAVA) believes that un- and under treated oral and dental diseases pose a significant animal welfare concern. Dentistry is an area of veterinary medicine which is still widely ignored and is subject to many myths and misconceptions. Effective teaching of veterinary dentistry in the veterinary school is the key to progression in this field of veterinary medicine, and to the improvement of welfare for all our patients globally. These guidelines were developed to provide veterinarians with the information required to understand best practices for dental therapy and create realistic minimum standards of care. Using the three-tiered continuing education system of WSAVA, the guidelines make global equipment and therapeutic recommendations and highlight the anaesthetic and welfare requirements for small animal patients. This document contains information on common oral and dental pathologies, diagnostic procedures (an easily implementable and repeatable scoring system for dental health, dental radiography and radiology) and treatments (periodontal therapy, extractions). Further, there are sections on anaesthesia and pain management for dental procedures, home dental care, nutritional information, and recommendations on the role of the universities in improving veterinary dentistry. A discussion of the deleterious effects of anaesthesia free dentistry (AFD) is included, as this procedure is ineffective at best and damaging at worst. Throughout the document the negative effects of undiagnosed and/or treated dental disease on the health and well-being of our patients, and how this equates to an animal welfare issue, is discussed.

Intraperitoneal and incisional analgesia in small animals: simple, cost-effective techniques.

The World Small Animal Veterinary Association Global Pain Council (WSAVA-GPC) has recently published its first "capsule review" by Monteiro et al. These are short articles that present a brief assessment of the scientific evidence and practical recommendations on important, and sometimes controversial, subjects in pain management. The capsules will be published regularly in the Journal of Small Animal Practice, the official journal of the WSAVA. This second article discusses the use of intraperitoneal and incisional analgesia in small animal practice, including their limitations and recommendations by the authors.

Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats.

This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2mg/kg (day 2 and 3) and 1mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables.

Impact of 24-h cooling prior to freezing on the survival of domestic cat (Felis catus) epididymal sperm.

The aim of this study was to investigate the impact of a 24-h cooling period prior to freezing on domestic cat epididymal sperm viability. Fifteen tomcats were submitted to routine orchiectomy and sperm samples were retrieved from both epididymides in a Tris-glucose-20% egg yolk extender. For each tomcat, the diluted sperm was split into two equal volumes and cooled to 5 degrees C at a rate of 0.5 degrees C/min; one sample for 60 min (control) and the other for 24 h (cooled). After the cooling period, samples from both groups were frozen using an identical freezing protocol. Sperm samples were evaluated in three different periods: immediately after harvesting, after cooling at 5 degrees C for 24 h (cooled group) and after freezing-thawing of control and cooled groups. Evaluations consisted of sperm motility and progressive status, sperm morphology and plasma membrane integrity (PMI) using two fluorescent probes. After cooling for 24 h, a decrease (p < 0.05) in sperm motility, progressive status and PMI was observed when compared to sperm samples immediately after collection. Comparing the results obtained after thawing, no difference (p < 0.05) was found regarding sperm motility, progressive status, PMI and sperm morphology between control and cooled groups. The results from the present study show that cooling cat epididymal spermatozoa at 5 degrees C for 24 h prior to freezing does not lead to major damage of spermatozoa impairing the freeze-thaw process.

Antinociceptive effects of epidural buprenorphine or medetomidine, or the combination, in conscious cats.

The aim of this study was to compare the antinociceptive effects of epidural buprenorphine (EB), epidural medetomidine (EM) or epidural buprenorphine-medetomidine (EBM). Eight cats were studied. Thermal thresholds (TT) were measured by increasing the temperature of a probe placed on the thorax. Mechanical thresholds (MT) were measured through inflation of a modified blood pressure bladder to the cat's forelimb. After baseline measurements, EB (0.02 mg/kg), EM (0.01 mg/kg) or half of the doses of each drug (EBM) were administered. Data were analysed using anova (P < 0.05) and 95% confidence interval (CI). TT increased from 30 min to 1 h after EB and at 45 min after EM. MT increased from 45 min to 2 h after EB, from 15 min to 1 h after EM and at 30, 45 min and at 2 h after EBM. MT were significantly lower after EB than EM at 30 min. TT were above the upper 95%CI from 15 min to 24 h after EB, from 15 min to 4 h after EM and from 15 min to 8 h after EBM. MT were above the upper 95%CI from 15 min to 5 h, and at 8, 12 and 24 h after EB, from 15 min to 6 h after EM and from 15 min to 6 h and at 12 and 24 h after EBM. All treatments had similar onset. Overall, EB presented longer period of action than EBM and EM. The same magnitude of analgesia was achieved, but with fewer side effects when EBM was compared with EM.

Analgesia for cats after ovariohysterectomy with either buprenorphine or carprofen alone or in combination.

Eighty-four female cats undergoing ovariohysterectomy in a blinded, randomised, prospective clinical study were assigned to one of three groups of 28 to receive either 0.01 mg/kg buprenorphine (group B), 4 mg/kg carprofen (group C), or the same doses of both drugs (group BC). A dynamic and interactive visual analogue scale (DIVAS) from 0 to 100 mm, and a simple descriptive scale (SDS) from 0 to 4 were used to evaluate the cats' degree of analgesia and sedation for 24 hours postoperatively. There was no significant difference in the cats' sedation scores by SDS or DIVAS, and no difference in their pain scores by DIVAS. By SDS, the cats in group BC had significantly lower pain scores than the cats in group C (P<0.001) and group B (P<0.05). Nine of the cats in group B, nine in group C and five in group BC required rescue analgesia, and the cats in group C required rescue earlier than those in group B (P<0.05).

Long-term use of non-steroidal anti-inflammatory drugs in cats with chronic kidney disease: from controversy to optimism.

This is the first of a series of capsule reviews published by the World Small Animal Veterinary Association - Global Pain Council (WSAVA-GPC). Each of these short articles provides a brisk assessment of the scientific evidence in specific aspects of pain management, including analgesic techniques, recommendations and controversies surrounding their use. In this first capsule review, the scientific evidence available on the long-term use of non-steroidal anti-inflammatory drugs in cats with concomitant chronic pain and chronic kidney disease is discussed.

Sedative and cardiorespiratory effects of acepromazine or atropine given before dexmedetomidine in dogs.

To test the hypothesis that acepromazine could potentiate the sedative actions and attenuate the pressor response induced by dexmedetomidine, the effects of acepromazine or atropine were compared in six healthy adult dogs treated with this alpha2-agonist. In a randomised block design, the dogs received intravenous doses of either physiological saline, 0.05 mg/kg acepromazine or 0.04 mg/kg atropine, 15 minutes before an intravenous dose of 5 microg/kg dexmedetomidine. The dogs' heart rate was reduced by 50 to 63 per cent from baseline and their mean arterial blood pressure was increased transiently from baseline for 20 minutes after the dexmedetomidine. Atropine prevented the alpha2-agonist-induced bradycardia and increased the severity and duration of the hypertension, but acepromazine did not substantially modify the cardiovascular effects of the alpha2-agonist, except for a slight reduction in the magnitude and duration of its pressor effects. The dexmedetomidine induced moderate to intense sedation in all the treatments, but the dogs' sedation scores did not differ among treatments. The combination of acepromazine with dexmedetomidine had no obvious advantages in comparison with dexmedetomidine alone, but the administration of atropine before dexmedetomidine is contraindicated because of a severe hypertensive response.

Carprofen and buprenorphine prevent hyperalgesia in a model of inflammatory pain in cats.

A model of nociceptive threshold determination was developed for evaluation of NSAID analgesia in cats. In a crossover study, eight cats received carprofen (4 mg/kg), buprenorphine (0.01 mg/kg) or saline (0.3 ml) subcutaneously before intradermal kaolin injection on the antebrachium to induce mild inflammation. Pressure thresholds were measured at the injected site using blunt-ended pins advanced by manual inflation of a bladder within a bracelet. Bladder pressure was recorded as threshold (PT) at the behavioural end point. Baseline PT were recorded before kaolin injection (time 0). PT was measured at 2-10 h intervals for 52 h. PT below the lower 95% confidence interval (CI) of baseline values indicated hyperalgesia. After saline, hyperalgesia was detected from 2-6 h, 22-26 h, and at 30 and 36 h. After carprofen, PT remained within the 95% CI. After buprenorphine, PT remained within the 95% CI except at 2h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia.

Development of a pressure nociceptive threshold testing device for evaluation of analgesics in cats.

A pressure analgesiometric device was developed for unrestrained cats. Eleven cats were studied. Stimulation was via three rounded pins within a bracelet on the forearm. The pins were advanced by manual bladder inflation. Bladder pressure was measured using a strain gauge pressure transducer. The threshold was recorded at the behavioural end point. Thresholds were measured at 5 and 15min intervals for 2-4h, after removal/replacement of the cuff, for 120min after SC butorphanol (0.4mg/kg), and with mild skin inflammation at the testing site. Data were analysed using ANOVA. Pressure thresholds in untreated cats were around 150mmHg. The minimum interval for testing was established as 15min. Data were reproducible over 4h and beyond 24h. Thresholds in 5 cats increased (P<0.05) above baseline for 45min after butorphanol with a maximum increase of 270+/-182mmHg at 10min. Thresholds decreased with inflammation. The method appears suitable for feline analgesia investigations.

The lack of analgesic use (oligoanalgesia) in small animal practice.

Oligoanalgesia is defined as failure to provide analgesia in patients with acute pain. Treatment of pain in emergencies, critical care and perioperatively may influence patient outcomes: the harmful practice of withholding analgesics occurs in teaching hospitals and private practices and results in severe physiological consequences. This article discusses the prevalence, primary causes, species and regional differences and ways to avoid oligoanalgesia in small animal practice. Oligoanalgesia may be addressed by improving education on pain management in the veterinary curriculum, providing continuing education to veterinarians and implementing pain scales.

Sciatic and femoral nerve blockade using bupivacaine alone, or in combination with dexmedetomidine or buprenorphine in cats.

The aim of this study was to determine the onset and offset of antinociception after sciatic (ScN) and femoral (FN) nerve blocks. Six healthy adult cats (4.8±1.3years; 4.3±0.4 kg) were included in a randomised, crossover, blinded and controlled study. Following sedation with dexmedetomidine (25 µg/kg, intramuscular), each ScN and FN injection was performed using 0.1 ml/kg of saline (CONTROL), bupivacaine (0.46 per cent, 0.46 mg/kg; BUPI), bupivacaine and dexmedetomidine (1 µg/kg; BUPI-DEX) or bupivacaine and buprenorphine (2.5 µg/kg; BUPI-BUPRE). Atipamezole (250 µg/kg) was administered after injections. Paw withdrawal thresholds (PWT) and motor blockade were evaluated before sedation and up to 24 hours. The PWT were significantly increased at half an hour in CONTROL, from two to four hours in BUPI and BUPI-DEX when compared with baseline. Motor blockade was observed between one and three hours in treatments using bupivacaine. Ability to walk was significantly impaired in BUPI at half an hour to two hours, BUPI-DEX at one to two hours and BUPI-BUPRE at two hours. Antinociception was observed in BUPI between one and eight hours, and in BUPI-DEX and BUPI-BUPRE between one and four hours. This study could not demonstrate a benefit of administering bupivacaine with dexmedetomidine or buprenorphine in cats. Results in BUPI-DEX may have been biased by the administration of atipamezole.

Perceptions and opinions of Canadian pet owners about anaesthesia, pain and surgery in small animals.

OBJECTIVES: The aim of this study was to evaluate the perceptions and opinions of Canadian pet owners about anaesthesia, pain and surgery in dogs and cats. METHODS: Six Canadian veterinary hospitals participated. Each practice received 200 copies of a questionnaire that were distributed to pet owners. Questions regarding the use of analgesics, anaesthesia, surgery and onychectomy (cats) were included. Responses were transformed into ordinal scores and analysed with a Cochran-Mantel-Haenszel test. RESULTS: A total of 849 out of 1200 questionnaires were returned. Owners believed more frequently that analgesics are needed for surgical procedures than for the medical conditions. Owners rated as very important/important: "knowing what to expect during illness/injury/surgery" (99·3%), "being assured that all necessary analgesic drugs/techniques will be used" (98·6%), "being informed about procedures/risk" (98·5%), and having a board-certified anaesthesiologist (90·5%). Most owners agreed/partly agreed that pain impacts quality of life (94·2%), and affects their pet's behaviour (89·5%). Most respondents (69%) were women; they were significantly more concerned than men about anaesthesia, pain, cost and client-communication. Cat owners believed that analgesics were necessary for some procedures/conditions significantly more often than canine-only owners. Pet owners with previous surgery disagreed more frequently that "pain after surgery can be helpful" and that "pain in animals is easy to recognize" than those without previous surgery. Most owners think onychectomy should be banned in cats (56·4%). CLINICAL SIGNIFICANCE: This study identified important areas of client communication regarding pain and its control in pets.