Abstract
Mice used in biomedical research should have pain reduced to an absolute minimum through refinement of procedures or by the provision of appropriate analgesia. Vasectomy is a common and potentially painful surgical procedure carried out on male mice to facilitate the production of genetically modified mice. The aim of our study was to determine if 0.05mg/kg buprenorphine would ameliorate pain associated changes following abdominal vasectomy and to determine if the mouse grimace scale is an appropriate tool for the assessment of pain in this model. Eight male CBA mice underwent abdominal vasectomy as part of a genetically modified mouse-breeding programme. Here we assessed pain using a previously validated behaviour-based method and the mouse grimace scale. All mice received buprenorphine (0.05mg/kgs.c.) pre-surgery. Behaviour and grimace scores were compared between baseline (pre-surgery), 30min, 5h, 24h and 25h post surgery. Following 24h post-op, all mice were administered 5mg/kg meloxicam (s.c.) as additional analgesia. Significant increases in specific pain behaviours and mouse grimace scale score were found 30min post surgery. At 5h post surgery, scores were returning to baseline levels. Frequency of rearing was significantly decreased at both 30min and 5h post surgery compared to baseline, demonstrating a longer lasting change in normal exploratory behaviour. Buprenorphine (0.05mg/kg) was ineffective at ameliorating these pain-associated changes in CBA mice and should be considered inadequate at this dose. By 24h post surgery, pain associated behaviours, grimace scale and rearing had all returned to baseline levels. There was no change in pain behaviours or MGS following administration of meloxicam indicating that an additional dose of meloxicam does not appear to offer benefit at this point. Using the mouse grimace scale to assess pain in mice, appeared to be effective in the immediate post vasectomy period in CBA mice demonstrating the same duration of increased score as the pain associated behaviours.
Highlights
Prevention or alleviation of pain in laboratory animals is a fundamental requirement of in vivo research
Behavioural assessment of pain is highly time consuming (Wright-Williams, 2007), and so detailed manual analysis to identify changes in behaviour that are specific to each strain of mouse limit the number of analgesic regimens that can be studied
We studied a different strain of mice, CBA, and scored these specific pain behaviours associated with this procedure
Summary
Prevention or alleviation of pain in laboratory animals is a fundamental requirement of in vivo research. The production of GM mice requires the use of vasectomised males to induce pseudo pregnancy (Ittner and Götz, 2007) and this provides a useful model for assessing the pain associated with surgery. A number of previous studies have assessed pain following both scrotal and abdominal approach vasectomy and have identified key changes in behaviour considered to be pain related (Leach et al, 2012; Miller et al, 2012; Wright-Williams et al, 2007). Vasectomy via the scrotal approach was predicted to be less painful (Robinson et al, 2003), data has shown that there is likely no significant advantage to one approach over the other (Miller et al, 2012). A number of other studies have used this model, with the behaviour-based scoring system, to evaluate analgesic efficacy A number of other studies have used this model, with the behaviour-based scoring system, to evaluate analgesic efficacy (e.g. Wright-Williams et al, 2013)
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