Some cell lines, especially unoptimized or aggressive cell lines, produce signs in mice that can be interpreted as indicating pain, but it is not clear from the literature that ascites production itself is necessarily associated with pain. Gebhart (personal communication) evaluated pain in ascites production and found that possible pain associated with intraperitoneal administration of pristane in mice is no more significant than that observed with the administration of intraperitoneal saline.
In humans, intraperitoneal administration of drugs is generally perceived as mildly uncomfortable but not distressful or painful. In clinical experience in humans, abdominal tumors are rarely painful unless they invade the intestinal organs; and ascites fluid accumulation is not painful, although a large accumulation can cause distress and discomfort because it interferes with respiration. When ascites fluid accumulation does become uncomfortable, tapping of the fluid is perceived as a welcome relief-not painful. Therefore, in mice it is probably more important to perform needle taps frequently to avoid ascites fluid accumulation sufficient to cause distress.
However, some cell lines produce clinical signs in mice indicating distress, including anorexia, rapid breathing, hunched posture, hypothermia, and decreased activity. Those signs can be observed in any sick mouse, regardless of the cause, and are usually seen with poor mAb-producing, more-aggressive cell lines. (It is important to note that this depends on the cell line.) Also, cell lines can produce various pathologic changes in mice that vary with the cell line and may be associated with pain or distress (Jackson and others 1999a).
Clearly, data are required if one is to determine objectively whether the ascites method for producing mAb causes pain or distress in mice, but it is unclear what such data would have to be. There is no reliable scientific measurement of pain or distress in rodents. Although that statement is true with regard to our ability to know with certainty the levels of pain or distress that an animal is experiencing, there is some information on what might or might not cause pain or distress (NRC 1992). Current guidelines suggest that if a procedure might be expected to cause pain in humans, we should expect it to cause pain in animals. Very little other guidance is given, and, as stated above, there are no broadly accepted techniques for assessing the degrees of pain or distress in animals. In most instances, the standard approach is to assume that an animal is in distress if it is experiencing significant weight loss (such as a weight loss of greater than 15 or 20%) or if it stops taking food and water. Those measures might be useful as indicators of severe distress, but there is a shortage of data on weight gain and