Browsing by Author "Ward N"

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    Characterisation of the Behavioural Effects of a Thoracic Squeeze in Healthy Newborn Piglets
    (MDPI (Basel, Switzerland), 2021-08) Holdsworth SE; Kells NJ; Chidgey KL; Vallée E; Ward N; Mellor DJ; Beausoleil NJ
    A thoracic squeeze has been observed to cause both healthy and low vigour neonatal foals to enter a ‘less-responsive state’, characterised by loss of posture, eye closure and cessation of movement, from which they rapidly recover to express normal healthy behaviours when the squeeze is released. To date, there have been no systematic studies characterising the responses of healthy neonates of other mammalian species to a thoracic squeeze. We describe the responses of healthy newborn piglets (n = 17) to a standardised application of the thoracic squeeze and evaluate the effect of the method of squeeze application on the response. Neonatal piglets were squeezed around the chest with either a soft fabric rope as has been used in foals (n = 8) or a novel purpose-made inflation cuff (n = 9). Both methods were effective at inducing a less-responsive behavioural state in all piglets, with neural reflexes reduced or absent in over half of them. The inflation cuff appeared to induce the less-responsive state faster than the rope, and more piglets squeezed with the cuff remained in this state for the full 10-min squeeze. These findings suggest that the behavioural response of foals to thoracic squeezing can be generalised to neonates of other precocial mammalian species. This initial study provides a foundation for further research using the inflation cuff to explore mechanisms underlying the thoracic squeeze and ways in which it may be applied whilst performing husbandry procedures.
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    Comparison of electroencephalographic changes in response to acute electrical and thermal stimuli with the tail flick and hot plate test in rats administered with opiorphin
    (BioMed Central Ltd, 19/04/2018) Singh P; Kongara K; Harding D; Ward N; Dukkipati VSR; Johnson C; Chambers P
    Background The objective of this study was to compare the changes in the electroencephalogram (EEG) in response to noxious stimuli with tail flick and hot plate responses of rats administered opiorphin. Methods Female Sprague -Dawley rats (n = 8 per group) randomly received intravenous (IV) injection of morphine (1 mg/kg,) or opiorphin (2 mg/kg,) or saline (0.5 ml,) in each of the three testing methods (EEG, tail flick and hot plate). Each type of test (n = 24 per test) was conducted in different population of rats on separate occasions. The tail flick and hot plate latencies were recorded until 5 min after test drug administration to conscious rats. The EEG was recorded in anaesthetised rats subjected to noxious thermal and electrical stimuli after test drug administration. At the end of 5 min in each of the testing methods rats were administered naloxone subcutaneously (SC) (1 mg/kg) and the test procedure was repeated. Results There was no significant increase in the median frequency and spectral edge frequency (F50 & F95) of EEG, indicators of nociception, of morphine and opiorphin groups after noxious stimulation. Noxious stimuli caused a significant increase in both F50 and F95 of the saline group. An injection of naloxone significantly increased the F50, thus blocking the action of both opiorphin and morphine. There was a significant increase in the tail flick latency after administration of opiorphin and morphine as compared to the baseline values. Rats of morphine group spent significantly longer on the hot plate when compared to those of the opiorphin and saline groups. There was no significant difference in the hot plate latencies of opiorphin and saline groups. Conclusion The results of this study suggest that the analgesic effect of opiorphin occurs at the spinal level and it is not as effective as morphine at supraspinal level. It may be due to rapid degradation of opiorphin or limited ability of opiorphin to cross the blood brain barrier or a higher dose of opiorphin is required for its action in the brain. Pharmacokinetic/pharmacodynamics studies along with in vivo penetration of opiorphin in the cerebrospinal fluid are required for further evaluation of opiorphin analgesia.
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    Evaluating the Behavioural Responses of Healthy Newborn Calves to a Thoracic Squeeze
    (MDPI (Basel, Switzerland), 2022-04) Holdsworth SE; Kells NJ; Vallée E; Ward N; Mellor DJ; Beausoleil NJ; Von Keyserlingk M
    A thoracic squeeze has been observed to cause low-vigour neonates of various farmed mammal species, including calves, to enter a state of reduced responsiveness. The removal of the squeeze causes rapid recovery and the expression of normal, healthy behaviours. However, the responses of healthy calves to a thoracic squeeze have not yet been characterized. The responses of 16 healthy newborn calves to a thoracic squeeze are described, along with the effect of the squeeze's application method on the response. Calves aged between 12 and 36 h were subjected to the squeeze using a rope (n = 8) or an inflation cuff (n = 8). In total, 13 of the 16 calves were induced into a state of reduced responsiveness, though neural reflexes persisted in nearly all of them. The squeeze was discontinued for nearly half of those induced before the end of the 10-min period, either due to spontaneous arousal or physiological instability. Both methods of application were equally effective at inducing reduced responsiveness, though responses to the cuff appeared to be more rapid than those to the rope. These findings support previous research on piglets and foals, and suggest that the behavioural responses to a thoracic squeeze are generalised across neonates of precocial farmed mammals; the findings provide a foundation for further research exploring the mechanisms underlying the response and the benefits that its application may bring for the performance of husbandry procedures.
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    Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam.
    (Taylor and Francis Group, 2023-07-16) Kongara K; Purchas G; Dukkipati V; Venkatachalam D; Ward N; Hunt H; Speed D
    AIMS: To evaluate and compare the pharmacokinetics of IM and oral firocoxib, and IM meloxicam, and detect their effect on renal function and average daily gain (ADG) in lambs undergoing tail docking and castration. METHODS: Seventy-five male Romney lambs, aged 3-6 weeks, were randomised into five treatment groups (n = 15 per group): IM firocoxib (1 mg/kg); oral firocoxib (1 mg/kg); IM meloxicam (1 mg/kg); normal saline (approximately 2 mL, oral); or sham. Following the treatment administration, hot-iron tail docking and rubber ring castration were performed in all groups except the sham group, which did not undergo the procedures, but the animals were handled in the same manner as castrated and tail docked lambs. Blood samples were collected before and 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after treatment administration, and drug concentrations in plasma were quantified by liquid chromatography and mass spectrometry. Plasma urea and creatinine concentrations were determined at a commercial laboratory. Lamb body weights were recorded before and 2, 4 and 8 weeks after tail docking and castration. The pharmacokinetic analysis was carried out using a non-compartmental approach. Between-group and between-time-point differences were compared using mixed model analyses. RESULTS: There was no evidence for a difference in plasma elimination half-life between firocoxib given IM (LSM 18.6 (SE 1.4) hours), firocoxib given orally (LSM 18.2 (SE 1.4) hours), and meloxicam given IM (LSM 17. 0 (SE 1.4) hours). Firocoxib (IM) had a significantly greater volume of distribution (LSM 3.7 (SE 0.2) L/kg) than IM meloxicam (LSM 0.2 (SE 0.2) L/kg). Lambs in the meloxicam group had higher (p < 0.05) plasma urea and creatinine concentrations than those in the firocoxib, saline and sham groups. Lambs' ADG was decreased (p < 0.01) compared to the other treatment groups in the 0-2 week period following meloxicam administration. CONCLUSIONS AND CLINICAL RELEVANCE: Both formulations of firocoxib had a long plasma elimination half-life and large volume of distribution. There was a transient reduction in ADG in the meloxicam group, possibly due to mild renal toxicity. Comparative studies on dose-response effects of firocoxib and meloxicam in lambs following the procedures are required.
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    Pharmacokinetics and efficacy of a novel long-acting bupivacaine formulation for cornual nerve block in calves
    (Frontiers Media S.A., 2022-12-01) Venkatachalam D; Kells N; Chambers P; Jacob A; Ward N; Singh P; Soto-Blanco B
    Local anesthetics are commonly used in farm animals to provide analgesia for painful procedures but can cause adverse effects at high systemic concentrations. The pharmacokinetics and efficacy of a long-acting sucrose acetate isobutyrate (SAIB) bupivacaine formulation following cornual nerve block in calves were compared to lidocaine. Fourteen calves were randomly assigned to one of the treatment groups (i) 5% Bupivacaine-SAIB (BUP-SAIB), n = 7; or (ii) 2% lidocaine (LID), n = 7. Cornual nerve block was performed, and duration of effective analgesia was evaluated by nociceptive threshold testing using a hand-held pressure algometer. Blood samples were collected at various time points and plasma concentrations were analyzed by HPLC. Pharmacokinetic parameters were calculated using a non-compartmental model. The mechanical nociceptive thresholds showed that the novel formulation could desensitize the skin around the horn bud for 18.77 ± 8.88 h (range 8-36 h), compared to 0.79 ± 0.34 h (range 0.5-1.5 h) with lidocaine. The mean maximum plasma concentration (Cmax) of bupivacaine was 152.03 (SD 37.34) ng/mL and its Tmax was 0.39 (SD 0.13) h. The half-life of elimination was 32.79 ± 11.00 h and the rate of clearance was 0.12 ± 0.03 L h-1. No toxicity signs were seen after treatment in either group. The novel formulation produced long-lasting analgesia of several times greater duration than that produced by lidocaine. This study showed that the safety and efficacy of the SAIB formulation justifies further studies in a larger population of animals.