A comparison of abdominal and scrotal approach methods of vasectomy and the influence of analgesic treatment in laboratory mice

Abstract

Vasectomized mice are needed in the production of genetically-modified animals. The BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement recommended that vasectomy should be performed via an incision in the scrotal sac, rather than via laparotomy, arguing that the former could be less painful due to minimal tissue trauma. This study was undertaken to assess the validity of this recommendation. Mice underwent vasectomy via either abdominal or scrotal approach surgery. Mice were filmed for 15 min presurgery and at one, 24 and 48 h postsurgery. Data were obtained using automated behaviour recognition software (HomeCageScan). Meloxicam was administered either alone or combined with acetaminophen prior to surgery. A third group received only saline subcutaneously. Postsurgery behaviour changes were compared between groups at each time point. Exploratory behaviours such as rearing, walking and sniffing were most greatly reduced at one hour following surgery whereas the duration of grooming increased. By 48 h these changes had largely subsided. Results indicated mice undergoing scrotal approach surgery fared better at one hour postsurgery, but the magnitude of this was relatively insignificant compared with the overall effects of surgery. If the observed behaviour changes resulted from pain, results suggested there was no significant advantage of scrotal versus abdominal approach vasectomy. These and other recently obtained data on the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in mice suggest considerably larger doses of these or more potent analgesics, more precise monitoring of surgical outcomes, or a combination of these factors are needed to determine the extent of pain experienced by mice undergoing vasectomy. Of the total number of animals used in regulated procedures in the UK, genetically-modified animals has increased from 8% (1995) to 54% in 2010. 1 Almost all of these animals were mice, of which a significant proportion being males undergoing vasectomy for inducing pseudopregnancy in females for transgenic animal production. It is presently unknown whether these mice, and those currently involved in these types of studies, experience pain. Despite virtually no supporting evidence the BVAAWF/FRAME/RSPCA/ UFAW Joint Working Group on Refinement 2 recommended vasectomy should be performed via scrotal approach surgery, where the vas deferens could be accessed via a relatively minor incision. By comparison with laparotomy, avoiding incising the abdominal muscles bearing the weight of the viscera (ca. 30% of body mass) 2 was considered likely to be less painful. However, scrotal approach vasectomy also involves dissection and tearing of tissue to access the vas deferens, so significant postoperative pain remains likely.Behavioural analysis is a key method of identifying pain postsurgery in rats and mice. In addition to suppression of normal behaviours including walking and rearing, a range of discrete identifiable acts have been characterized following vasectomy including; belly pressin...

The Conditioned Place Preference Test for Assessing Welfare Consequences and Potential Refinements in a Mouse Bladder Cancer Model

“…This showed abnormal behaviour changes began between 7 and 10 days before the study ended, with the most notable effects being reduced distance travelled, reduced active and rearing behaviour and increased abdominal grooming. Changes to behaviours such as these have previously been attributed to abdominal pain in mice [30], [31], [56] and are similar to those that occur post-operatively in rats [21]. However, the most conclusive evidence that the mice actually experienced pain came from the CPP study.…”

“…However, morphine had little influence on grooming in normal mice, and there were indications of post-treatment reductions in grooming in the cancer groups (Figure 9c). Grooming behaviour has previously been concluded to be important for assessing effects due to abdominal surgery or other manipulation likely to induce acute visceral discomfort [30], [31], [56], [67], cancer [68], arthritis [69] and also shows pattern alterations during stress [70]. Perhaps consistent with stress, the cancer-bearing mice were less frequently inactive (unable to rest) prior to morphine (Figure 9d), but again, post-treatment effects were similar in all mice so no positive outcomes were detectable.…”

“…However, the guidelines that are meant to minimise suffering in these studies [10], [11] do not incorporate any evaluation of changes in underlying subjective state, and obtaining evidence of cancer pain in rodents has relied heavily on assessing underlying nociceptive changes [12]–[15], and it seems this is still the case today [16]–[19]. Our group has extensively assessed changes in naturalistic behaviours as a means of assessing post-operative pain in rodents and other species using both manual [20]–[26] and automated methods [27]–[30], or used a combination of both types of analysis [31]. However, such behaviour analysis has rarely been used to assess the effects of cancer, and those few studies that cite ‘pain behaviour’ actually mean nociceptive or nocifensive behaviours (i.e.…”

Comparative Effects of Vasectomy Surgery and Buprenorphine Treatment on Faecal Corticosterone Concentrations and Behaviour Assessed by Manual and Automated Analysis Methods in C57 and C3H Mice

“…This simplifies the scoring process and requires minimal training [18] and so provides a practicable ‘cage-side’ method of assessing pain in either singly or group housed animals. Although we have used the pain-specific approach in vasectomised mice given different doses of meloxicam [2] or paracetamol [10], or these drugs combined [9], it was not more effective than activity monitoring. It was possible to differentiate between normal and surgery groups using pain-specific scoring, but not between groups given different dose rates of analgesics.…”

The power of automated behavioural homecage technologies in characterizing disease progression in laboratory mice: A review

“…Compared to behavioural changes that occur with progressive disease, the automated detection of behavioural changes that occur in pain states have been relatively well described (e.g. Roughan et al, 2009;Miller et al, 2011Miller et al, , 2012Urban et al, 2011;Wright-Williams et al, 2013;Whittaker and Howarth, 2014), and will therefore not be discussed further here.…”