Claire Richardson

Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures

A structured literature review was carried out to assess recent trends in the administration of analgesics and anaesthetics to laboratory rats and mice undergoing surgical procedures. The ScienceDirect database was used to systematically identify studies published in peer-reviewed journals over two periods (2000–2001 and 2005–2006), 86 studies from each time period were included in the review. The total number of animals that underwent surgery, species used, type of procedure, anaesthetic regimen and analgesic administration were noted for each study. There was an increase in the reported administration of systemic analgesics from 10% in 2000–2001 to 20% in 2005–2006. Buprenorphine was the most commonly reported analgesic in both periods (2000–2001: 78%, 2005–2006: 35%) and reporting the use of non-steroidal anti-inflammatory drugs increased from 11% to 53%. There was also a change in reported anaesthetic practices, notably a decrease in the use of pentobarbital and an increase in the use of isoflurane and ketamine/xylazine. Although reported administration of analgesics has increased and there has been some refinement in the selection of anaesthetic agents used, the findings of this review suggest that there is still significant scope for improvement with respect to the perioperative care of laboratory rodents.

Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse

Abstract Behaviour was assessed in 32 C57BL/6JCrl and 32 C3H/HeN male mice 1 h following vasectomy; saline or meloxicam was administered 30 min prior to surgery at 5, 10, or 20 mg kg−1. Faeces were collected 24 h prior to, and 3, 6, 9, 12, 24 h following, vasectomy for measurement of faecal corticosterone. Peak corticosterone levels were significantly higher in mice that underwent vasectomy and received saline (p < 0.001) or meloxicam at 5 or 10 mg kg−1 (p = 0.021, and p < 0.001, respectively) compared with normal un‐operated controls. Mice that underwent vasectomy and received 20 mg kg−1 meloxicam had peak corticosterone levels that were not different from normal un‐operated mice (p = 0.254). Discriminant analysis was used to identify behaviours responsible for group separation; these were summed to create two behaviour scores. Score 2 (the frequency of flinching, writhing, rear leg lift and press 2) was thought to be pain related; mice that underwent vasectomy and received saline exhibited significantly more of these behaviours than the normal controls (p = 0.032), and the mice that received meloxicam (at any dose). Strain differences were observed in both the stress response to vasectomy and the behavioural changes; the C3H/HeN mice had higher pain scores (behaviour Score 2) and peak corticosterone responses than the C57BL/6JCrl mice. We have demonstrated that significant changes occur in the behaviour of mice following vasectomy, and these changes are reduced by use of meloxicam. Vasectomy elicits a rise in corticosterone levels that was only reduced by the highest dose of meloxicam.

Behavioural effects of ovariohysterectomy and oral administration of meloxicam in laboratory housed rabbits.

This study aimed to develop a behaviour-based pain assessment system for rabbits following ovariohysterectomy. Behaviour was analysed to assess the severity and duration of pain induced and determine the effects of administration of meloxicam. The results suggest that pain associated with ovariohysterectomy induced changes in the frequency and duration of a number of behaviours. The most indicative was inactive pain behaviour, which was observed very infrequently prior to surgery compared to very frequently immediately following surgery. This strongly suggests that this increase is a direct response to the surgical pain and/or stress. The frequency of inactive pain behaviour also decreased over the four days post-surgery suggesting that pain is decreasing during this time. High dose meloxicam (initial 1mg/kg followed 0.5mg/kg/day) induced some degree of analgesia. However, higher doses of meloxicam or in combination with an opioid may be required to provide consistent analgesia in rabbits following soft-tissue surgery.

Are We Looking in the Wrong Place? Implications for Behavioural-Based Pain Assessment in Rabbits (Oryctolagus cuniculi) and Beyond?

Background Successful observation of behaviour depends upon knowing both which behaviours to look for and focusing on the appropriate areas of the body to observe them. Behaviour based scoring systems have become increasingly widely used to assess animal pain and distress. Although studies are available demonstrating which behaviours need to be observed, there has been little attempt to assess how effectively observers apply such information when viewing an animals behaviour. Methodology/Principal Findings This study used historical video recordings of New Zealand white rabbits (Oryctolagus cuniculi) considered to be experiencing varying degrees of post-operative pain to assess the pattern of observation and the ability to assess pain exhibited by both experienced and inexperienced human participants (n = 151). Eye tracking equipment was used to identify how quickly, how frequently, for how long different areas of the rabbits body were attended to by the participants. Simple visual analgoue scoring was used to assess the pain experienced in each sequence. The results demonstrate that irrespective of their experience or gender, observers focus first, more frequently and for longer on the face, compared to the abdomen, ears, back and hindquarters of the rabbit and that participants were poor at identifying rabbits in pain. Observing the back and hindquarters was correlated with ‘correct’ assessments and observing the face was correlated with ‘incorrect’ assessments. Conclusions In conclusion, irrespective of experience and gender, observers focused on the face when using behaviour to assess pain and were unable to effectively identify rabbits in pain. Focusing on the face is unlikely to be effective when using behavioural indicators of pain since they involve other body areas. Alternatively, if animals exhibit pain-related facial expressions, then it could improve our ability to assess pain. In addition, these results have potential implications for the use of behaviour to assess how rabbits and potentially other species feel.

Reported analgesic administration to rabbits, pigs, sheep, dogs and non-human primates undergoing experimental surgical procedures

Reported analgesic use following experimental surgery is low in rodents and there has been little published information on the frequency of analgesic use in other laboratory species. A structured literature review was conducted to examine analgesic administration in larger laboratory animals. The Scirus search engine was used to identify studies published in peer-reviewed journals that reported carrying out experimental surgery on ‘large’ laboratory animals, specifically rabbits, pigs, sheep, dogs and non-human primates. Seventy-four studies between 2000 and 2001 and 75 studies between 2005 and 2006 were included in the review. There was an increase in the reported administration of systemic analgesics to these species from 50% in 2000–2001 to 63% in 2005–2006. When all agents with analgesic properties were considered (systemic analgesics, local anaesthetics and anaesthetics with analgesic components), the proportion of papers that reported some form of analgesic administration to ‘large’ laboratory animals increased from 86% in 2000–2001 to 89% in 2005–2006. Overall rabbits, pigs, sheep, dogs and non-human primates were more likely to receive analgesics following potentially painful experimental procedures than has been reported in laboratory rodents but analgesic administration to ‘large’ laboratory species is still not optimal.

Reported analgesic administration to rabbits undergoing experimental surgical procedures

BackgroundIt has become widely accepted that whenever animals are used in scientific procedures, the 3Rs principle of replacement, reduction and refinement described by William Russell and Rex Burch should be adhered to. Animals should be replaced with non-sentient alternatives if possible, the number of animals used should be reduced and experimental procedures should be refined to minimise pain, suffering and distress. Administration of analgesic agents to animals undergoing surgical procedures is a refinement used to alleviate pain. In this study, a structured literature review was carried out to examine current trends in analgesic administration to rabbits undergoing experimental surgical procedures.Results128 papers from 51 peer-reviewed journals were selected for inclusion in this review. Reporting administration of systemic analgesia to rabbits in peer-reviewed scientific papers increased significantly from 16% to 50% between 1995-1997 and 2005-2007 (P < 0.001). Papers that reported ethical approval were more likely than papers that did not specify approval to report systemic analgesic administration (P < 0.001). When systemic analgesics were administered, buprenorphine was the most frequently used agent and non-steroidal anti-inflammatory drugs were used less frequently than opioids in both time periods.ConclusionsAlthough this review provides evidence that systemic analgesic administration to rabbits undergoing surgical procedures is increasing, rabbits do not always receive analgesia when they undergo experimental surgery. Other practices in rabbit perioperative care that could be improved, highlighted by this survey include: 1) changing the timing of analgesic administration by giving systemic analgesics pre- or perioperatively rather than only postoperatively, 2) using multimodal analgesia when pain is likely to be moderate to severe and 3) increasing the use of non-steroidal anti-inflammatory drugs and use of other techniques such as epidural analgesia particularly for orthopaedic procedures.

Creation of porcine liver tumor using human hepatoma cell lines: experimental study.

Background : Pig is an ideal animal to study the efficacy of surgical and ablative treatment options available for the treatment of liver tumours. But there is no liver tumour model available in pig. This experiment was carried out to create liver tumours in the pig using immunosuppression and portal tolerance. Material & methods: Two mini pigs( specific pathogen free) were immunosuppressed using cyclosporine, azathioprine and prednisolone immunotherapy. Human hepatoma cell line (HepG2) was delivered into the liver through portal vein injection. Engraftment of the tumour cell was monitored using regular measurement of serum alfa- fetoprotein level (AFP). Pigs were sacrificed at the end of 6 weeks to confirm any evidence of tumour in the liver. Result: Although there was rise in serum AFP level in the first week, tumour cells did not engraft in the liver and there was no evidence of liver tumour at the end of experiment. Conclusion: Effect of immunosuppression and portal tolerance does not prevent rejection of human hepatoma cells by porcine immune system.

Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eμ-myc lymphoma

Background:Non-invasive biomarkers of disease progression in mice with cancer are lacking making it challenging to implement appropriate humane end points. We investigated whether body temperature, food and water consumption could be used to predict tumour burden.Methods:Thirty-six male, wild-type C57Bl/6 mice were implanted with subcutaneous RFID temperature sensors and inoculated with Eμ-myc tumours that infiltrate lymphoid tissue.Results:Decrease in body temperature over the course of the study positively predicted post-mortem lymph node tumour burden (R2=0.68, F(1,22)=44.8, P<0.001). At experimental and humane end points, all mice that had a mean decrease in body temperature of 0.7 °C or greater had lymph nodes heavier than 0.5 g (100% sensitivity), whereas a mean decrease in body temperature <0.7 °C always predicted lymph nodes lighter than 0.5 g (100% specificity). The mean decrease in food consumption in each cage also predicted mean post-mortem lymph node tumour burden at 3 weeks (R2=0.89, F(1,3)=23.2, P=0.017).Conclusion:Temperature, food and water consumption were useful biomarkers of disease progression in mice with lymphoma and could potentially be used more widely to monitor mice with other forms of cancer.

Routine neutering of rabbits and rodents

CONSIDERATION should be given to neutering rabbits, guinea pigs and rats to prevent unwanted litters, limit undesirable behaviours that accompany sexual maturity, prevent disease and treat reproductive disease. Numerous surgical approaches, using a variety of safe and effective anaesthetic and analgesic agents, have been described for the routine neutering of rabbits and rodents, but these may be less familiar to veterinary surgeons in practice than the techniques used for dogs and cats. This article illustrates how to conduct an ovariohysterectomy and castration in rabbits, guinea pigs and rats, reviewing the surgical techniques that the authors have found to be particularly successful in these species.

Rodents: anaesthesia and analgesia

Veterinary surgeons may be wary of anaesthetizing rodents as they are often less familiar with these species. Rodent anaesthesia can be challenging because, although the various species of rodent tend to be physically similar, they often differ in their response to anaesthetics. Similarly, the drug effects vary with the age, sex and strain of the animal. The relatively short life span of these species can result in a high proportion of aged patients being anaesthetized. For example, a 30-month-old rat presented for removal of a mammary tumour should be considered geriatric. These factors may explain why anaesthetic mortality in rodents has been higher than for other small animals such as dogs and cats. The general considerations are that of risk factor reduction, prevention of hypothermia, respiratory depression and analgesia. The chapter looks at Preanaesthetic preparations; Choice of anaesthetic; Intraoperative care and anaesthetic monitoring; Dealing with anaesthetic emergencies; and Postoperative care.