Identifying behavioural differences in working donkeys in response to analgesic administration.

REASONS FOR PERFORMING STUDY: To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. OBJECTIVES: To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). STUDY DESIGN: Observer-blinded, placebo-controlled trial. METHODS: Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20). Observation of postural and event behaviours was undertaken at 2 pretreatment time points followed by 4 post treatment time points, using scan (instantaneous) and focal sampling. RESULTS: In comparison to pretreatment baselines, donkeys receiving meloxicam were more alert post treatment than the placebo group. They were observed lying down less frequently (P = 0.007), with their eyes closed less frequently (P = 0.04) and having a high head carriage more frequently (P = 0.02). Dozing behaviour decreased after meloxicam compared with the pretreatment baseline (P = 0.03). Donkeys given meloxicam also showed more interest in their environment, turning to look at environmental stimuli more frequently (P = 0.05) than those in the placebo group post treatment. Neither the meloxicam nor the placebo group showed a significant post treatment improvement in lameness scores. CONCLUSIONS: Working donkeys receiving meloxicam were more active and alert compared with their pretreatment behaviour, confirming the potential value of nonsteroidal anti-inflammatory drugs in identifying behaviours indicative of pain in working donkeys. Behavioural assessment of pain in working donkeys in field clinic conditions will enable veterinary staff and owners to identify welfare issues promptly and monitor response to analgesia. The Summary is available in Chinese--see Supporting information.

Clinical abnormalities in working donkeys and their associations with behaviour.

INTRODUCTIONS: Working donkeys are at risk of developing multiple, acute and chronic health problems. The ability to recognise and assess pain in donkeys associated with these health problems is important for people responsible for their care and treatment, including owners and veterinary or animal health workers. AIMS AND OBJECTIVES: The aims of this study were firstly to quantify the prevalence of a range of clinical abnormalities within a sample of working donkeys; and secondly to find out whether these abnormalities were associated with potential behavioural indicators of pain. MATERIALS AND METHODS: One hundred and thirty-three entire male adult working donkeys were observed for ten minutes before and after a one-hour rest period. Using an ethogram developed and refined in associated studies, posture and event behaviours were recorded by a single observer. The health of each donkey was then assessed by a veterinarian for specific clinical abnormalities. RESULTS: Working donkeys have a high prevalence of clinical abnormalities and a number of behaviours are associated with these. Significant associations were found between observed behaviours and systemic, ocular and limb-related clinical abnormalities. Cumulative clinical scores for limb-related problems were associated with a higher frequency of leg trembling, knuckling of the forelimb, leg-lifting and weight-shifting behaviours (all R≥0.4; P<0.001) and with a lower frequency of weight-bearing evenly on all four feet (R=-0.458; P<0.001). CONCLUSIONS: The specific behaviour changes associated with clinical abnormalities identified in this study, together with general changes in demeanour identified in related studies, may be useful in assessing the presence and severity of pain in working donkeys and their response to medical and palliative interventions.

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.

Development of mechanical and thermal nociceptive threshold testing devices in unrestrained birds (broiler chickens).

Behavioural signs of pain are difficult to quantify and interpret in animals. Nociceptive threshold testing is therefore a useful method for examining the perception and processing of noxious stimuli underlying pain states. Devices were developed to measure response thresholds to quantified, ramped mechanical and thermal nociceptive stimuli applied to the leg or keel of unrestrained birds. Up to 9N mechanical force was delivered via a single round-ended 2mm pin using a pneumatic actuator at 0.4Ns(-1). Heat was applied through a small copper element at 0.8°Cs(-1) to a maximum of 50°C. The repeatability and reliability of threshold measures were validated using 10-12 broiler chickens (aged 49-66 days) per site and modality. Mechanical threshold, or skin and threshold temperature, were recorded over three sessions across a 36h period. Both stimulus types elicited clear, reproducible behavioural responses. Mechanical threshold means and 95% confidence intervals were 3.0 (2.8-3.2)N for keel and 2.0 (1.8-2.1)N for leg sites. Keel thermal tests gave a mean skin temperature of 39.3 (39.1-39.5)°C, and threshold of 46.8 (46.6-47.1)°C. Leg skin temperature was 35.7 (35.6-35.9)°C and threshold 42.5 (42.2-42.8)°C. Threshold measures were consistent within and across sessions and birds showed individual repeatability across tests within sessions. Individual birds' mechanical keel thresholds were also repeatable across sessions. The apparatus gave reliable, reproducible measurements of thresholds to noxious mechanical and thermal stimuli. The range recorded was comparable with previously published nociceptor thresholds in dissected chicken nerve filament fibres, and the method appears suitable for studying nociceptive processes in broiler chickens.

Assessment of the sedative effects of buprenorphine administered with 20 microg/kg detomidine in horses.

The aim of this randomised, observer-blinded, crossover study was to compare the effects of four treatments, administered intravenously to six horses: saline and saline; 10 µg/kg detomidine and 7.5 µg/kg buprenorphine; 20 µg/kg detomidine and 7.5 µg/kg buprenorphine; and 20 µg/kg detomidine and 10 µg/kg buprenorphine. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation and duration of sedation were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Increasing the dose of detomidine from 10 to 20 µg/kg increased the degree of sedation when administered with the same dose of buprenorphine (7.5 µg/kg). When administered with 20 µg/kg detomidine, increasing the dose of buprenorphine from 7.5 to 10 µg/kg did not influence the degree of sedation achieved.

Assessment of the sedative effects of buprenorphine administered with 10 µg/kg detomidine in horses.

The aim of this randomised, observer-blinded, crossover study was to compare the effects of six treatments, administered intravenously to six horses: saline and saline (S/S); detomidine and saline (D/S); detomidine and 5 µg/kg buprenorphine (D/B5); detomidine and 7.5 µg/kg buprenorphine (D/B7.5); detomidine and 10 µg/kg buprenorphine (D/B10); and detomidine and 25 µg/kg butorphanol (D/BUT). The detomidine dose was 10 µg/kg for all treatments in which it was included. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation, duration of sedation and the area under the curve (AUC) for sedation scores were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Peak sedation and duration of sedation were statistically significantly different between treatments (P<0.001). No sedation was apparent after administration of S/S. The AUC was significantly different between treatments (P=0.010), with S/S being significantly different from D/S, D/BUT, D/B5 and D/B7.5, but not D/B10 (P=0.051).

Effects of two doses of buprenorphine four or six hours apart on nociceptive thresholds, pain and sedation in dogs after castration.

Twenty-eight dogs were randomly allocated into two groups. They were premedicated with either 10 or 20 microg/kg buprenorphine and 0.05 mg/kg acepromazine administered intramuscularly, and then anaesthetised with intravenous thiopentone to effect and maintained with isoflurane in 100 per cent oxygen. The dogs underwent routine castration, and a second dose of 10 microg/kg buprenorphine was administered four hours after the first or 20 microg/kg six hours after the first dose. Levels of pain and sedation were scored on a visual analogue scale and in terms of the dogs' requirement for rescue analgesia, and mechanical nociceptive thresholds were measured at the hock and wound at premedication and one, two, three, four, five, six, seven, 10 and 21 to 22 hours later. Pain scores were low in both groups, with a trend for lower scores in the high dose group; administration of the second dose of buprenorphine further decreased the pain scores. Buprenorphine produced good preoperative sedation and the level of sedation decreased over time after surgery. Administration of the second high dose of buprenorphine did not increase the level of sedation. Both doses of buprenorphine prevented hyperalgesia at the wound and hock postoperatively. Three dogs given the low dose and one dog given the high dose required rescue analgesia with carprofen.

Role of ketoprofen in the modulation of hyperalgesia associated with lameness in dairy cattle.

Forty lame dairy cows were randomly assigned to receive a course of either the non-steroidal anti-inflammatory drug ketoprofen, or sterile saline, together with conventional treatment for lameness. The effect of the ketoprofen was measured by using locomotion scoring and by testing the cows' nociceptive threshold over a period of 28 days. The locomotion score of all the cows improved but ketoprofen had no significant effect on this change. However, in the cows that received ketoprofen the hyperalgesia associated with lameness, recorded using a nociceptive threshold test, was significantly modulated on days 3, 8 and 28 after their initial examination, drug administration and treatment of lesions.

Comparison between meloxicam and carprofen for postoperative analgesia after feline ovariohysterectomy.

Eighty female cats presented for ovariohysterectomy were randomly allocated to one of two treatment groups in this assessor-blinded trial. After pre-anaesthetic assessment, the cats were premedicated with acepromazine (0.1 mg/kg). Anaesthesia was induced with thiopentone and maintained with halothane in oxygen. Forty cats received carprofen (4 mg/kg subcutaneously) and 40 received meloxicam (0.3 mg/kg subcutaneously) after anaesthetic induction. Following routine flank ovariohysterectomy the cats were assessed using visual analogue scale scores for pain and sedation over a 20-hour study period. Blood samples were taken before sedation and at 20 hours for serum biochemistry (urea, creatinine, alanine aminotransferase and aspartate aminotransferase). There were no significant differences between the groups for pain and sedation scores. Serum biochemistry values were similar between the groups, with some differences within groups between the pre-sedation and 20-hour values. One cat in the carprofen group and two cats in the meloxicam group required rescue analgesia with intramuscular morphine (0.2 mg/kg).

Use of a new finger-mounted device to compare mechanical nociceptive thresholds in cats given pethidine or no medication after castration.

Mechanical nociceptive thresholds are regularly used to determine the efficacy of analgesic agents both experimentally and clinically in a variety of species. The 'pressure of palpation device' (PPD) was developed for use in cats and is a small battery operated device with a finger-mounted force sensing resistor (FSR, Interlink Electronics, Northumberland. UK). The PPD was used in a study assessing the analgesic efficacy of pethidine after castration in cats. Pethidine was demonstrated to prevent the development of post-operative scrotal hypersensitivity for up to 2 hours after castration, whereas cats given no analgesics showed marked hyperalgesia immediately after surgery. Visual Analogue Scale (VAS) pain scores after castration showed a similar analgesic effect of pethidine. These results suggest that the PPD could become a useful research tool to assess the effectiveness of analgesic agents in the cat.

Analgesic effects in dogs of carprofen and pethidine together compared with the effects of either drug alone.

Thirty bitches undergoing routine neutering were used in an assessor-blinded trial of the postoperative analgesic effects of pethidine and carprofen administered either together or singly. The level of analgesia was assessed by visual analogue scale (VAS) scores for pain and sedation and by nociceptive mechanical threshold testing. The two drugs administered together, and carprofen alone, provided good postoperative analgesia as assessed by VAS scoring. Pethidine alone did not provide postoperative analgesia of sufficient duration.

Postoperative analgesia in the cat after ovariohysterectomy by use of carprofen, ketoprofen, meloxicam or tolfenamic acid.

The adequacy of postoperative analgesia was assessed in 40 cats following ovariohysterectomy. At extubation, cats were given one dose of carprofen, ketoprofen, meloxicam or tolfenamic acid. Postoperative analgesia was assessed using visual analogue scale (VAS) scoring for pain and sedation; measurement of mechanical nociceptive thresholds at the wound; recognition of the requirement for rescue intervention analgesia; and an overall clinical assessment score at 18 hours. VAS pain scores were low throughout the trial, with no significant differences found between the groups. Postoperative mechanical nociceptive thresholds decreased significantly from baseline in all four groups, with no significant differences between the groups. One cat in each of the tolfenamic acid, ketoprofen and meloxicam groups required rescue intervention analgesia. Nine out of 10 cats in all four groups were classified as having desirable overall clinical assessment scores. In summary, all four drugs provided good postoperative analgesia, although none was able to prevent postoperative wound tenderness.

The post-operative analgesic effects of ketamine after canine ovariohysterectomy--a comparison between pre- or post-operative administration.

Thirty-six female dogs undergoing ovariohysterectomy were randomly allocated into three groups in this assessor-blinded study. The control group received no ketamine, the preketamine group were given ketamine (2.5 mg kg(-1)i.m.) at anaesthetic induction (in addition to the induction agents), the post-ketamine group received ketamine (2.5 mg kg(-1)i.m.) at extubation. Mechanical nociceptive thresholds and visual analogue scale (VAS) scores were measured before premedication and post-operatively at 20 minutes, 1, 2, 4, 8 and 18 hours after extubation. Dogs in the control group required more rescue analgesics than those in the other two groups (significantly more than the preketamine group), they also had consistently higher VAS pain scores throughout the post-operative period. Administration of ketamine post-operatively delayed the onset of post-operative wound hyperalgesia; dogs in the control group had the greatest amount of post-operative wound hyperalgesia. A single subanaesthetic dose of ketamine provided effective but short acting analgesia and preoperative administration may confer some benefits over administration post-operatively.

Self-selection of the analgesic drug carprofen by lame broiler chickens.

Lame and sound broilers, selected from commercial flocks, were trained to discriminate between different coloured feeds, one of which contained carprofen. The two feeds were then offered simultaneously and the birds were allowed to select their own diet from the two feeds. In an initial study to assess the most appropriate concentration of drug, the plasma concentrations of carprofen were linearly related to the birds' dietary intake. The walking ability of lame birds was also significantly improved in a dose-dependent manner and lame birds tended to consume more analgesic than sound birds. In a second study, in which only one concentration of analgesic was used, lame birds selected significantly more drugged feed than sound birds, and that as the severity of the lameness increased, lame birds consumed a significantly higher proportion of the drugged feed.

Antinociceptive effects of intrathecal 5-HT agonists in sheep.

OBJECTIVES: To examine the role of spinal 5-hydroxytryptamine (5-HT) binding sites in nociceptive processing in conscious sheep and to study the role of 5-HT agonists in mediating analgesia. STUDY DESIGN: Prospective controlled study. ANIMALS: Nine adult healthy female sheep (Swaledale, Swaledale-cross or Clun Forest) weighing 45-65 kg. METHODS: Intrathecal (IT) catheters were implanted at the cervical (n = 5) or lumbar (n = 4) level of the spinal cord under general anaesthesia. At least 1 week later, and at 1 week intervals thereafter, the effects of intrathecal Ringer's solution (control), xylazine (100 µg), 5-HT creatinine sulphate (200, 400 and 800 µg), RU24969 (200 µg), α-Methyl-5-HT and 1-(3-Chlorophenyl)-biguanide (CPBG) on the mechanical nociceptive threshold (MT) were studied. Results were plotted as mean variable versus time curves. Areas under portions of the curves (0-30 and 0-60 minutes) were measured and expressed as mean ± standard error. Differences between values for control and drug trials were examined using the two-tailed Student's t-test. RESULTS: Baseline values of MT were lower on the hind limbs than on the forelimbs. Intrathecal Ringer's solution did not alter MT in the cervical or lumbar region. Xylazine (100 µg) produced a characteristic elevation in MT between 5 and 60 + minutes. Lumbar IT injection of 5-HT (800 µg) raised the MT more than cervical injection, while cervical injection of RU24969 (200 µg) raised the MT more than lumbar administration. Cervical IT injection of α-Me-5-HT (500 µg) produced a marked and significant increase in MT while lumbar application had no effect. CPBG (500 µg) injection caused no significant effect on MT with either cervical or lumbar applications. CONCLUSIONS: The activation of 5-HT1 and 5-HT2 receptors particularly at the cervical level appears to be involved in spinal nociceptive processing in the sheep. CLINICAL RELEVANCE: These effects, which lasted about 60 minutes, may have an implication in the development of new analgesic strategies for animals.

Current British veterinary attitudes to perioperative analgesia for dogs.

In March 1996, a questionnaire was sent to 2000 veterinary surgeons, primarily involved in small animal practice, to assess their attitudes to perioperative analgesic therapy in dogs, cats and other small mammals. This paper is concerned only with the data relating to dogs. The veterinary surgeons considered that pain was a consequence of all the surgical procedures specified, but there were differences in their treatment of pain. Some veterinarians considered that a degree of pain was necessary postoperatively to prevent excessive activity. In general, women and more recent graduates assigned higher pain scores to the procedures and were more likely to treat the pain with analgesics. A significant number of veterinarians consider the use of opiates or non-steroidal anti-inflammatory drugs before surgical procedures, but relatively few appear to use combinations of different classes of analgesics either before or after operations.