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Opioids are a key component of multimodal analgesia. Methadone is licensed in Europe for IV, IM and SC use in dogs despite there being no published studies assessing the analgesic efficacy of SC administration. Our intention was to compare the analgesic effect of IV or SC methadone. Fifteen dogs presenting for stifle surgery were administered 0.4 mg/kg methadone IV followed by a randomised 0.0.4 mg/kg methadone IV or SC dose 3 h later. All dogs received ultrasound-guided sciatic and saphenous nerve blocks with bupivacaine prior to surgery. This protocol resulted in opioid adverse effects (hypersalivation, vomiting and/or regurgitation) in 5/15 dogs (33%). Thus, in consultation with the ethical review committee, an otherwise identical protocol using a revised 0.2 mg/kg methadone dose was implemented. In the next three dogs studied, similar opioid adverse effects were found in all three dogs and the study was terminated. This paper highlights the potential for post operative nausea and vomiting (PONV), which may have been induced by methadone when used in combination with efficacious locoregional anaesthesia., Competing Interests: Conflict of interest statement None of the authors had any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

This study investigated the influence of bupivacaine infiltration before or after hemilaminectomy on peri-operative opioid requirement in dogs. Thirty dogs undergoing T3-L3 hemilaminectomy were randomly assigned to receive peri-incisional infiltration of bupivacaine 2 mg/kg into the epaxial muscles before surgery (Group A), at wound closure (Group B), or no infiltration (Group C). Anaesthesia comprised dexmedetomidine 4 mcg/kg and methadone 0.3 mg/kg IV (premedication), alfaxalone IV (induction), and isoflurane in oxygen (maintenance). All dogs received meloxicam SC/PO prior to induction of general anaesthesia. Response to surgery, defined as a change in autonomic physiological variables >20% above baseline, was treated with fentanyl 2.5 mcg/kg boluses, followed by a continuous rate infusion of fentanyl at 5 mcg/kg/h. The Glasgow Composite Pain Score-Short Form (GCPS-SF) was performed before premedication and at regular intervals until 24 h postoperatively. Methadone 0.2 mg/kg analgesia was given IV if GCPS-SF was ≥5/20. Number of intraoperative, postoperative and total analgesic interventions were recorded. Analgesic interventions were analysed using a chi-squared test using a Pocock approach and statistical significance was set at P < 0.029. The number of intra-operative analgesic interventions in Group A (median, 0; range, 0-2), was significantly lower than in Group B (median, 3; range, 0-5) and Group C (median, 3; range, 0-5; P = 0.019). Regarding postoperative interventions, there were significantly fewer in Group A (median, 0; range, 0-1) and Group B (median, 0; range, 0-1) than in Group C (median, 1; range, 0-2; P = 0.047). Group A (median, 0; range, 0-3), had significantly fewer total analgesic interventions than Group B (median, 3; range, 0-6) and Group C (median, 4; range, 1-7; P = 0.014). Bupivacaine reduced peri-operative opioid administration and pre-surgical peri-incisional infiltration yielded the greatest benefit., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate the sedative effects of medetomidine in combination with midazolam or butorphanol for routine imaging procedures in dogs. Eighty client owned dogs were recruited in a prospective, randomised, blinded clinical study and randomly assigned to receive one of four treatments intramuscularly (IM): (1) 30μg/kg medetomidine (Med30); (2) 20μg/kg medetomidine combined with 0.3mg/kg butorphanol (Med20But0.3); (3) 20μg/kg medetomidine combined with 0.3mg/kg midazolam (Med20Mid0.3); and (4) 10μg/kg medetomidine combined with 0.3mg/kg midazolam (Med10Mid0.3). The level of sedation was evaluated using a composite sedation scale assessed by one investigator (0=no sedation, 15=profound sedation). The number of dogs deemed to be adequately clinically sedated and the dose of propofol administered as rescue sedation were recorded. Mean±standard deviation sedation scores at 30min after the commencement of treatment in the groups that received Med20But0.3 (9.8±4) and Med20Mid0.3 (8.9±4.4) were not statistically significantly different from each other, but were significantly different from the group receiving Med10Mid0.3 (5.6±3.6). Only Med20But0.3 was significantly associated with adequate clinical sedation, while Med10Mid0.3 was associated with 85% sedation failure. The rescue sedation dose of propofol (1.5±1mg/kg) for the Med10Mid0.3 group was significantly higher than for other treatments. A sedation score≥10 out of 15 was a satisfactory cut-off to predict adequate clinical sedation. In healthy dogs, the combination of medetomidine with midazolam did not provide comparable sedation to the same dose of medetomidine in combination with butorphanol in a clinical setting., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

This study investigated the effects of osteoarthritis (OA) on somatosensory processing in dogs using mechanical threshold testing. A pressure algometer was used to measure mechanical thresholds in 27 dogs with presumed hind limb osteoarthritis and 28 healthy dogs. Mechanical thresholds were measured at the stifles, radii and sternum, and were correlated with scores from an owner questionnaire and a clinical checklist, a scoring system that quantified clinical signs of osteoarthritis. The effects of age and bodyweight on mechanical thresholds were also investigated. Multiple regression models indicated that, when bodyweight was taken into account, dogs with presumed osteoarthritis had lower mechanical thresholds at the stifles than control dogs, but not at other sites. Non-parametric correlations showed that clinical checklist scores and questionnaire scores were negatively correlated with mechanical thresholds at the stifles. The results suggest that mechanical threshold testing using a pressure algometer can detect primary, and possibly secondary, hyperalgesia in dogs with presumed osteoarthritis. This suggests that the mechanical threshold testing protocol used in this study might facilitate assessment of somatosensory changes associated with disease progression or response to treatment., (Copyright © 2017. Published by Elsevier Ltd.)

This study aimed to analyse UK pharmacovigilance data to quantify adverse events (AEs) associated with the non-steroidal anti-inflammatory drug (NSAID) molecules found in veterinary medicines authorised for use in dogs and cats. It was hypothesised that the frequency of AEs would be lower when associated with cyclo-oxygenase-2 selective (coxib), compared to non-selective (non-coxib) NSAIDs. The UK Veterinary Medicines Directorate (VMD) supplied frequencies of AEs derived from Periodic Safety Update Reports subdivided by formulation and species for each NSAID molecule. Frequencies of AEs were similar between species. The five most reported AEs were emesis, death, anorexia, lethargy, and diarrhoea. Reported frequency of emesis, renal insufficiency and death was higher with injectable compared to oral NSAIDs (P = 0.043). Reported frequency of emesis, lethargy and death was higher with coxib, compared to non-coxib NSAIDs (P = 0.029). Median (range) interval since authorisation was shorter for coxibs at 5 (2.5-9) years compared to non-coxibs at 15 (12-25) years. A negative correlation between time elapsed since authorisation and the frequency of AEs was identified (rs = -0.11 to -0.94). Higher frequency of reported AEs with injectable NSAIDs may be related to perioperative administration. The AE frequency associated with coxib and non-coxib NSAIDs may be confounded by changes in reporting habits over time. This study highlights the value of interrogating passive surveillance data to identify low frequency AEs and the need to facilitate improvement in recording and collecting AEs in small animal practice., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Mechanical threshold (MT) testing is widely used to measure nociceptive thresholds. However, there has been little research into factors that contribute to the response rate and repeatability (collectively termed 'efficacy') of MT testing protocols. The aim of this study was to investigate whether the efficacy of a protocol using a hand-held algometer to measure MTs (N) in healthy dogs (n = 12) was affected by varying (1) the area over which force was applied (tip diameter), (2) rate of force application, (3) position of dog during testing, and (4) anatomical site of testing. The effect of these factors on MT and the impact of individual dog effects on both efficacy and MT were also investigated. Overall, 3175/3888 tests (82%) resulted in a measurable response. The response rate was reduced by using wider tip diameters, testing at the tibia, and testing when the dog was lying down (compared to sitting upright). Wider tips were associated with higher, more variable MTs (mean ± standard deviation) with values of 4.18 ± 2.55 N for 2 mm diameter tips, 5.54 ± 3.33 for those of 4 mm, and 7.59 ± 4.73 for 8 mm tips. Individual dog effects had the most significant impact on efficacy and MT. The findings indicate that tip diameter, dog position, and anatomical site may affect both protocol efficacy and MTs, and should be taken into account when comparing different studies and in designing protocols to measure MTs in dogs. The predominant effect of the individual dog over other factors indicates that between-subject differences should always be accounted for in future studies., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

An observer blinded, placebo controlled study evaluated the effects of 62.5 μg/m(2) dexmedetomidine administered IV on recovery from isoflurane anaesthesia in dogs. Forty-four healthy dogs, weighing 1.8-19.95 kg, presented for surgery that was expected to cause mild to moderate pain were studied. All were premedicated with 125 μg/m(2) dexmedetomidine and 20 μg/kg buprenorphine IM. Anaesthesia was induced with propofol and maintained with isoflurane. Non-steroidal anti-inflammatory drugs and local anaesthetics were administered as appropriate. Immediately prior to extubation dogs were treated with dexmedetomidine 62.5 μg/m(2) (group D) or an equivalent volume of heparinised saline (S). Assessments of heart rate, respiratory rate, pain (short form Glasgow composite pain scale [SF-GCPS], dynamic interactive visual analogue scale [DIVAS]), sedation (simple descriptive scale [SDS], DIVAS) and mechanical nociceptive threshold (MNT) were performed immediately before premedication, 20 min later, at the time of test drug administration (T0) and at 15-30 min intervals for four hours (T240 min). Recovery quality was scored 0 - 3 (SDS). Data were analysed with Student's t and Mann-Whitney U tests, two-way ANOVA and Fisher's exact test. Significantly fewer poor quality recoveries were observed in group D (D 2 [1-3]; S 2 [0-3]; P=0.02), however, sedation was increased in group D compared to group S from T15 to T150 min (P=0.0001). Pain scores were lower in group D compared to group S from T15 to T120 min (P=0.001), but the requirement for additional analgesia in the first 4h following extubation was not different between groups. Dexmedetomidine may decrease the incidence of poor quality anaesthetic recoveries in dogs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Pain associated with poultry lameness is poorly understood. The anti-nociceptive properties of two non-steroidal anti-inflammatory drugs (NSAIDs) were evaluated using threshold testing in combination with an acute inflammatory arthropathy model. Broilers were tested in six groups (n=8 per group). Each group underwent a treatment (saline, meloxicam (3 or 5mg/kg) or carprofen (15 or 25mg/kg)) and a procedure (Induced (arthropathy-induction) or sham (sham-handling)) prior to testing. Induced groups had Freund's complete adjuvant injected intra-articularly into the left intertarsal joint (hock). A ramped thermal stimulus (1°C/s) was applied to the skin of the left metatarsal. Data were analysed using random-intercept multi-level models. Saline-induced birds had a significantly higher skin temperature (± SD) than saline-sham birds (37.6 ± 0.8°C vs. 36.5 ± 0.5°C; Z=-3.47, P<0.001), consistent with an inflammatory response. Saline was associated with significantly lower thermal thresholds (TT) than analgesic treatment (meloxicam: Z=2.72, P=0.007; carprofen: Z=2.58, P=0.010) in induced birds. Saline-induced birds also had significantly lower TT than saline-sham birds (Z=-2.17, P=0.030). This study found direct evidence of an association between inflammatory arthropathies and thermal hyperalgesia, and showed that NSAID treatment maintained baseline thermal sensitivity (via anti-nociception). Quantification of nociceptive responsiveness in a predictable broiler pain model identified thermal anti-hyperalgesic properties of two NSAIDs, which suggested that therapeutically effective treatment was provided at the doses administered. Such validation of analgesic strategies will increase the understanding of pain associated with specific natural broiler lameness types., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Leg health of intensively reared broiler chickens is a significant problem, yet little is known regarding the nature of lameness-associated pain. Kinematic changes in gait have been reported in naturally lame broilers following subcutaneous non-steroidal anti-inflammatory drug (NSAID) administration, compared to a placebo group. In the current study, an extensive range of gait parameters were defined using a commercial motion-capturing system to record three-dimensional temporospatial information from walking broilers pre- and post-treatment. Data analysis, performed using multi-level models, revealed gait modifications in broilers receiving NSAID, but not in those receiving saline. The effect of walking velocity was accounted for retrospectively. An increase in velocity following NSAID treatment (carprofen: P<0.001; meloxicam: P=0.044) indicated improved walking ability. For several measures, the polarity of the treatment effect depended upon walking speed. At slow speeds certain parameters become more like those of non-lame broilers, which may have been indicative of improved stability: stride length and duration (both NSAIDs), transverse back displacement (meloxicam), and vertical leg displacement (carprofen). However, these same parameters also revealed that NSAID treatment caused imbalance at faster speeds, which may have signified an excessive dosage. Although doses employed were not conclusively effective, evidence was provided that factors besides body conformation influenced mobility in the test cohort. The study showed that the model would be useful in future studies to increase our understanding of pain associated with specific lameness types in broiler chickens., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Naloxone can enhance the antinociceptive/analgesic effects of buprenorphine in humans and rats. The antinociceptive effects of a patented 15:1 buprenorphine:naloxone combination was investigated in cats using a thermal and mechanical nociceptive model. Twelve cats received buprenorphine 10 μg/kg, naloxone 0.67 μg/kg or a buprenorphine-naloxone combination intramuscularly in a randomised cross over study. Using thermal and mechanical analgesiometry validated in the cat, pre-treatment baselines were measured. Following test drug administration, thresholds were studied for the next 24h. Naloxone did not enhance the thermal antinociceptive effect of buprenorphine. The results from this study are in agreement with previously published work showing that naloxone antagonises the effects of clinically analgesic doses of buprenorphine. Mechanical nociceptive thresholds were not affected by buprenorphine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)