Post-operative nausea and vomiting (PONV) observed in a clinical study designed to assess the analgesic effects of intravenous and subcutaneous methadone in dogs.

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.

Influence of peri-incisional epaxial muscle infiltration with bupivacaine pre- or post-surgery on opioid administration in dogs undergoing thoraco-lumbar hemilaminectomy.

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.

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.

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.

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.

Randomised clinical trial comparing clinically relevant sedation outcome measures in dogs after intramuscular administration of medetomidine in combination with midazolam or butorphanol for routine diagnostic imaging procedures.

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.

A comparison between methadone and buprenorphine for perioperative analgesia in dogs undergoing ovariohysterectomy.

OBJECTIVE: To investigate whether preoperative methadone provides superior perioperative analgesia compared to buprenorphine in dogs undergoing ovariohysterectomy. METHODS: Eighty female dogs were recruited to an assessor-blinded, randomised, clinical trial. Dogs received a premedication dose of 0·05 mg/kg acepromazine or 10 µg/kg medetomidine combined with either 0·3 mg/kg methadone or 20 µg/kg buprenorphine intramuscularly. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed using two scoring schemes (a dynamic interactive visual analogue scale and the short form of the Glasgow Composite Pain Scale) before premedication, 30 minutes later and every hour for 8 hours after premedication. If indicated, rescue analgesia was provided with methadone. Meloxicam was administered after the final assessment. The area under the curve for change in pain scores over time and the requirement for rescue analgesia were compared between groups. RESULTS: Groups premedicated with buprenorphine had significantly higher pain scores than those premedicated with methadone. There was no interaction between opioid and sedative for any outcome measure. Rescue analgesia was required by significantly more dogs premedicated with buprenorphine (45%) than that of methadone (20%). CLINICAL SIGNIFICANCE: At the doses investigated, methadone produced superior postoperative analgesia compared to buprenorphine in dogs undergoing ovariohysterectomy.

Comparative Genomics and Mutational Analysis Reveals a Novel XoxF-Utilizing Methylotroph in the Roseobacter Group Isolated From the Marine Environment.

The Roseobacter group comprises a significant group of marine bacteria which are involved in global carbon and sulfur cycles. Some members are methylotrophs, using one-carbon compounds as a carbon and energy source. It has recently been shown that methylotrophs generally require a rare earth element when using the methanol dehydrogenase enzyme XoxF for growth on methanol. Addition of lanthanum to methanol enrichments of coastal seawater facilitated the isolation of a novel methylotroph in the Roseobacter group: Marinibacterium anthonyi strain La 6. Mutation of xoxF5 revealed the essential nature of this gene during growth on methanol and ethanol. Physiological characterization demonstrated the metabolic versatility of this strain. Genome sequencing revealed that strain La 6 has the largest genome of all Roseobacter group members sequenced to date, at 7.18 Mbp. Multilocus sequence analysis (MLSA) showed that whilst it displays the highest core gene sequence similarity with subgroup 1 of the Roseobacter group, it shares very little of its pangenome, suggesting unique genetic adaptations. This research revealed that the addition of lanthanides to isolation procedures was key to cultivating novel XoxF-utilizing methylotrophs from the marine environment, whilst genome sequencing and MLSA provided insights into their potential genetic adaptations and relationship to the wider community.

An investigation of mechanical nociceptive thresholds in dogs with hind limb joint pain compared to healthy control dogs.

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.

Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential.

The attine ants of South and Central America are ancient farmers, having evolved a symbiosis with a fungal food crop >50 million years ago. The most evolutionarily derived attines are the Atta and Acromyrmex leafcutter ants, which harvest fresh leaves to feed their fungus. Acromyrmex and many other attines vertically transmit a mutualistic strain of Pseudonocardia and use antifungal compounds made by these bacteria to protect their fungal partner against co-evolved fungal pathogens of the genus Escovopsis. Pseudonocardia mutualists associated with the attines Apterostigma dentigerum and Trachymyrmex cornetzi make novel cyclic depsipeptide compounds called gerumycins, while a mutualist strain isolated from derived Acromyrmex octospinosus makes an unusual polyene antifungal called nystatin P1. The novelty of these antimicrobials suggests there is merit in exploring secondary metabolites of Pseudonocardia on a genome-wide scale. Here, we report a genomic analysis of the Pseudonocardia phylotypes Ps1 and Ps2 that are consistently associated with Acromyrmex ants collected in Gamboa, Panama. These were previously distinguished solely on the basis of 16S rRNA gene sequencing but genome sequencing of five Ps1 and five Ps2 strains revealed that the phylotypes are distinct species and each encodes between 11 and 15 secondary metabolite biosynthetic gene clusters (BGCs). There are signature BGCs for Ps1 and Ps2 strains and some that are conserved in both. Ps1 strains all contain BGCs encoding nystatin P1-like antifungals, while the Ps2 strains encode novel nystatin-like molecules. Strains show variations in the arrangement of these BGCs that resemble those seen in gerumycin gene clusters. Genome analyses and invasion assays support our hypothesis that vertically transmitted Ps1 and Ps2 strains have antibacterial activity that could help shape the cuticular microbiome. Thus, our work defines the Pseudonocardia species associated with Acromyrmex ants and supports the hypothesis that Pseudonocardia species could provide a valuable source of new antimicrobials.

Refinement of a thermal threshold probe to prevent burns.

Thermal threshold testing is commonly used for pain research. The stimulus may cause burning and merits prevention. Thermal probe modifications hypothesized to reduce burning were evaluated for practicality and effect. Studies were conducted on two humans and eight cats. Unmodified probe 0 was tested on two humans and promising modifications were also evaluated on cats. Probe 1 incorporated rapid cooling after threshold was reached: probe 1a used a Peltier system and probe 1b used water cooling. Probe 2 released skin contact immediately after threshold. Probe 3 (developed in the light of evidence of 'hot spots' in probe 0) incorporated reduced thermal mass and even heating across the skin contact area. Human skin was heated to 48℃ (6℃ above threshold) and the resulting burn was evaluated using area of injury and a simple descriptive scale (SDS). Probe 1a cooled the skin but required further heat dissipation, excessive power, was not 'fail-safe' and was inappropriate for animal mounting. Probe 1b caused less damage than no cooling (27 ± 13 and 38 ± 11 mm(2) respectively, P = 0.0266; median SDS 1.5 and 4 respectively, P = 0.0317) but was cumbersome. Probe 2 was unwieldy and was not evaluated further. Probe 3 produced even heating without blistering in humans. With probe 3 in cats, after opioid treatment, thermal threshold reached cut-out (55℃) on 24 occasions, exceeded 50℃ in a further 32 tests and exceeded 48℃ in the remainder. No skin damage was evident immediately after testing and mild hyperaemia in three cats at 2-3 days resolved rapidly. Probe 3 appeared to be suitable for thermal threshold testing.

A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery.

REASONS FOR PERFORMING STUDY: Buprenorphine, a µ-agonist opioid, has recently been licensed for equine use, but butorphanol, a κ-agonist opioid, is more commonly used in horses. The effect of the 2 opioids has not previously been compared in a large clinical study. OBJECTIVES: To compare post operative analgesia and physiological variables in horses undergoing elective surgery following premedication with either buprenorphine or butorphanol in a conventional clinical setting. STUDY DESIGN: Multicentre, prospective, randomised, blinded clinical investigation. METHODS: Eighty-nine healthy horses admitted for elective surgery to one of 6 UK equine veterinary clinics were premedicated with acepromazine, a nonsteroidal anti-inflammatory drug, and romifidine followed by intravenous (i.v.) buprenorphine or butorphanol. Anaesthesia was induced with diazepam/ketamine and maintained with isoflurane in oxygen. A range of surgical procedures were performed and supplementary anaesthetic agents given as required. Physiological variables were monitored during anaesthesia and pain, ataxia, sedation and vital function were assessed post operatively. Data were analysed using t-tests, ANOVA, Mann-Whitney U-test and Chi-squared test as appropriate and P<0.05 was regarded as significant, except for multiple comparisons, when P<0.01 was used. RESULTS: Surgery was carried out successfully in all cases and no mortality or serious morbidity occurred. Physiological variables remained within normal limits and all horses recovered successfully, most standing within 1 h of ceasing anaesthesia. There were no significant differences between groups in any variable except post operative pain when scores (simple descriptive scale) between 3 and 6 h were significantly lower after buprenorphine than after butorphanol. CONCLUSIONS: Horses experienced less post operative pain after buprenorphine than after butorphanol premedication. Compared with butorphanol, buprenorphine did not cause any different effects on vital function.

Influence of experimental protocol on response rate and repeatability of mechanical threshold testing in dogs.

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.

Prescription of perioperative analgesics by UK small animal veterinary surgeons in 2013.

Data from a survey conducted in 1996-1997 suggested a low level of perioperative analgesic administration to cats and dogs in the UK. In order to evaluate current practice and attitudes with regards to perioperative analgesic prescription, a cross-sectional survey of UK practising small animal veterinary surgeons was undertaken in spring 2013. Four thousand one hundred paper questionnaires were distributed and the survey was made available online. Seven hundred and twenty valid responses were received and analysed. All respondents had access to at least one non-steroidal anti-inflammatory drug (NSAID) and one opioid within their practice. Respondents considered analgesic efficacy, and degree of intraoperative pain, the most important factors governing their selection of NSAID and opioid analgesics. Perioperative NSAIDs were administered by approximately 98 per cent of respondents to dogs and cats undergoing neutering. Multimodal (opioid+NSAID) analgesia was prescribed by the majority of respondents. Neutering was considered more painful in dogs than in cats, and lower rates of opioid and postdischarge NSAID prescription were reported for cats. Orthopaedic, abdominal and dental surgeries were considered equally painful in dogs and cats. Local analgesic techniques were not commonly used. Analgesic prescription has increased since previous surveys, which should translate to improved animal welfare.

Spontaneous electroencephalographic changes in a castration model as an indicator of nociception: a comparison between donkeys and ponies.

REASONS FOR PERFORMING STUDY: Donkeys are believed to be less demonstrative of pain than ponies. Research into comparative sensory processing between these species is required to elucidate these behavioural differences. OBJECTIVES: To compare changes in the electroencephalogram (EEG) recorded during castration between donkeys and ponies. STUDY DESIGN: Prospective clinical study. METHODS: Six ponies and 6 donkeys were castrated under halothane anaesthesia after acepromazine premedication and thiopental anaesthetic induction. Markers were inserted into the EEG recording at the time of skin incision (skin) and emasculation (emasc) for both testicles (T1 and T2) during a closed castration. Raw EEG data were analysed and the EEG variables median frequency (F50 ), total power (Ptot ) and spectral edge frequency (F95 ) derived using standard techniques. Baseline values of F50 , Ptot and F95 for each animal were used to calculate the percentage change from baseline at T1skin, T2skin, T1emasc and T2emasc. RESULTS: Decreased F50 values relative to baseline were observed in 4 ponies and 2 donkeys across all castration time points. In the remaining animals, the F50 value increased compared with baseline. Both donkey and pony groups showed an overall decrease in Ptot values compared with baseline at T1skin, but the magnitude of the decrease was significantly less (P = 0.004) in ponies than in donkeys. Donkeys demonstrated an overall greater increase (P = 0.05) in F95 values at T1skin relative to baseline compared with ponies. CONCLUSIONS: Electroencephalographic responses to the noxious stimulus of castration were noted in both donkeys and ponies. Donkeys demonstrated a greater change in Ptot in response to castration than ponies; thus, donkeys appear to demonstrate a cerebral cortical response to a noxious stimulus that is similar to or greater than that in ponies, suggesting that their subtle behavioural expression of pain is not due to a difference in cortical processing of noxious sensory stimuli.

Objective validation of central sensitization in the rat UVB and heat rekindling model.

BACKGROUND: The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were utilized to objectively demonstrate validity of the rat UVB/HR model. METHODS: The UVB/HR model was induced on the heel of the hind paw under anaesthesia. Mechanical withdrawal thresholds (MWTs) were obtained from biceps femoris EMG responses to a gradually increasing pinch at the mid hind paw region under alfaxalone anaesthesia, 96 h after UVB irradiation. MWT was compared between UVB/HR and SHAM-treated rats (anaesthetic only). Underlying central mechanisms in the model were pharmacologically validated by MWT measurement following intrathecal N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, or saline. RESULTS: Secondary hyperalgesia was confirmed by a significantly lower pre-drug MWT {mean [±standard error of the mean (SEM)]} in UVB/HR [56.3 (±2.1) g/mm(2) , n = 15] compared with SHAM-treated rats [69.3 (±2.9) g/mm(2) , n = 8], confirming face validity of the model. Predictive validity was demonstrated by the attenuation of secondary hyperalgesia by MK-801, where mean (±SEM) MWT was significantly higher [77.2 (±5.9) g/mm(2) n = 7] in comparison with pre-drug [57.8 (±3.5) g/mm(2) n = 7] and saline [57.0 (±3.2) g/mm(2) n = 8] at peak drug effect. The occurrence of central sensitization confirmed construct validity of the UVB/HR model. CONCLUSIONS: This study used objective outcome measures of secondary hyperalgesia to validate the rat UVB/HR model as a translational model of inflammatory pain.

Comparison of premedication with buprenorphine or methadone with meloxicam for postoperative analgesia in dogs undergoing orthopaedic surgery.

OBJECTIVES: To determine whether methadone, administered before orthopaedic surgery, results in improved postoperative analgesia compared to buprenorphine. METHODS: Thirty-eight dogs undergoing orthopaedic surgeries (the majority being tibial tuberosity advancement or elbow arthrotomy) were premedicated with 0 · 03 mg/kg acepromazine and either 20 µg/kg buprenorphine or 0 · 5 mg/kg methadone, intramuscularly, allocated randomly. Anaesthesia was induced with propofol intravenously to effect and maintained with isoflurane in oxygen. 0 · 2 mg/kg meloxicam was administered at anaesthetic induction. Sedation was assessed by means of a dynamic interactive visual analogue and simple descriptive scales and pain by dynamic interactive visual analogue and the short form Glasgow composite pain scales, by a single observer blinded to treatment group at intervals for 8 hours following premedication. RESULTS: Sedation scores were higher than baseline in both groups following premedication until the end of the assessment period (P = 0 · 0001), with no differences between groups. Pain scores were lower overall in dogs premedicated with methadone (dynamic interactive visual analogue scale P = 0 · 048; short form Glasgow composite pain scale P = 0 · 0045), and these dogs required less additional analgesia (42%, compared to 79% premedicated with buprenorphine, P = 0 · 045). CLINICAL SIGNIFICANCE: At the doses investigated, methadone produced superior analgesia to buprenorphine for 8 hours postoperatively in dogs undergoing orthopaedic surgery.

Lame broiler chickens respond to non-steroidal anti-inflammatory drugs with objective changes in gait function: a controlled clinical trial.

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.

Perioperative socialization, care and monitoring of National Institutes of Health miniature swine undergoing ocular surgery and sampling of peripheral blood.

Swine are a frequent species of choice for testing new surgical procedures and for transplantation studies. However, information concerning best practice to prepare pigs for surgery and postoperative treatment and monitoring is limited, despite a perception that preoperative socialization is beneficial. Therefore we examined the effect of preoperative visits by project personnel on compliance of 26 National Institutes of Health (NIH) minipigs subject to corneal transplantation. We briefly describe sedation and anaesthesia protocols developed for surgery and multiple postoperative interventions in order to facilitate interpretation of data relating to pig compliance. Preoperative visit variables and measures of preoperative socialization were correlated with postoperative outcome. Principal component analysis (PCA) of postoperative outcome variables identified a factor accounting for 53.5% of the variance that was significantly associated with two factors derived from PCA of preoperative factors (accounting, respectively, for 54.7% and 26.0% of the variance; P = 0.019 for the overall model, P = 0.041 and 0.040 for factors 1 and 2, respectively), such that more time spent with pigs before surgery and higher socialization scores were associated with less postoperative stress and difficulty of eye medication. Moreover, two of the preoperative visit variables, time spent with only one person in the pen and time spent with two or more people in the pen, contributed predominantly to PCA factors 1 and 2, respectively, indicating that they were fulfilling two qualitatively different requirements for socialization. We conclude that NIH minipigs are fully compliant with anaesthetic and postoperative experimental procedures provided they are well-socialized to project personnel before surgery.

Buprenorphine in combination with naloxone at a ratio of 15:1 does not enhance antinociception from buprenorphine in healthy cats.

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.