Assessing the welfare of mice used in cancer research
Lead Research Organisation:
Newcastle University
Department Name: Institute of Neuroscience
Abstract
Large numbers of mice are used in cancer research to try to develop new treatments for people. A major public concern about these animals and any other animals used in research, is whether this causes them to feel any pain. It should be easy to determine this, but it is not. At present, scientists try to minimize any pain or distress by assessing the animals carefully, and humanely killing them if they are thought to be suffering. The way we make these assessments may not be very effective, so it is important that we develop better methods so we can treat animals as humanely as possible.
In people, it is the emotions that we experience when we are in pain that make it so unpleasant, so it is important to measure how pain feels to mice. If we can do this, then we can make a much better assessment of how their welfare is affected during different types of research.
This project will measure how much pain that mice used in cancer research may experience in several ways. We will measure changes to the systems that detect pain; we will measure the behavioural changes that occur as tumours grow to identify changes that may indicate pain, and we will use two methods that let mice show how much pain they may be feeling by the choices they make when given analgesics.
Combining all of this information will let us establish when pain occurs with different types of cancer, how much pain occurs, and how we can detect this by carefully observing the mice. Once we have successfully used the methods that let mice tell us how they feel in this study of cancer pain, we will also be able to use the methods in many different types of research. This will let us assess how much pain they may experience much more accurately, and let us decide how best to limit or eliminate that pain.
In people, it is the emotions that we experience when we are in pain that make it so unpleasant, so it is important to measure how pain feels to mice. If we can do this, then we can make a much better assessment of how their welfare is affected during different types of research.
This project will measure how much pain that mice used in cancer research may experience in several ways. We will measure changes to the systems that detect pain; we will measure the behavioural changes that occur as tumours grow to identify changes that may indicate pain, and we will use two methods that let mice show how much pain they may be feeling by the choices they make when given analgesics.
Combining all of this information will let us establish when pain occurs with different types of cancer, how much pain occurs, and how we can detect this by carefully observing the mice. Once we have successfully used the methods that let mice tell us how they feel in this study of cancer pain, we will also be able to use the methods in many different types of research. This will let us assess how much pain they may experience much more accurately, and let us decide how best to limit or eliminate that pain.
Technical Summary
Mice are widely used in cancer research. This may cause pain and distress to the animals but few studies have assessed how much pain this causes and whether this is a major welfare concern. To apply appropriate humane endpoints (and effective cost-benefit analyses of projects) we urgently need to objective assessments and not the relatively arbitrary guidelines that are used currently.
We have already obtained preliminary evidence that bladder cancer causes pain in mice, but variation in tumour growth meant we were unable to establish firm guidelines on an appropriate (humane) end-point. In this study we will use several different approaches to address these issues. We will assess long term behaviour changes (using automated analyses developed in our previous project), peripheral sensitivity changes and new techniques designed to address the problem of assessing the affective component of pain (how it makes animals ?feel?). Parallel imaging studies will monitor cancer growth, so that we can determine how these different measures of pain and nociception change in animals with tumours. The measures of subjective/affective state are especially important, since it remains possible that the behavioural and other signs we attribute to pain actually have limited welfare consequences. We will use two methods, the conditioned place preference paradigm (CPP) and conditional drug discrimination. In the CPP paradigm whether mice are feeling pain as tumours develop can be inferred by whether their preference for an environment where previously they were exposed to an analgesic (morphine) progressively increases. If mice are ?feeling? pain, in conditioned drug discrimination studies they should be able to be trained to use changes in this (due to analgesic treatment) as a cue to perform a task for a food reward. If the degree of pain is of little consequence, or if they do not have an internal state of ?what it is like to be in pain?, they would not show enhanced morphine seeking in the CPP paradigm, and would fail distinguish between the analgesic and saline in drug discrimination trials.
Correlating theses measures of subjective state with changes in behaviour, peripheral sensitisation and measures of tumour growth will give is a clearer picture of the pain caused by different types of tumour. This will allow us to refine endpoints in cancer studies. Of potentially even greater importance is that we will have established new methods for assessing the welfare consequences of other potentially painful procedures applied in laboratory rodents.
We have already obtained preliminary evidence that bladder cancer causes pain in mice, but variation in tumour growth meant we were unable to establish firm guidelines on an appropriate (humane) end-point. In this study we will use several different approaches to address these issues. We will assess long term behaviour changes (using automated analyses developed in our previous project), peripheral sensitivity changes and new techniques designed to address the problem of assessing the affective component of pain (how it makes animals ?feel?). Parallel imaging studies will monitor cancer growth, so that we can determine how these different measures of pain and nociception change in animals with tumours. The measures of subjective/affective state are especially important, since it remains possible that the behavioural and other signs we attribute to pain actually have limited welfare consequences. We will use two methods, the conditioned place preference paradigm (CPP) and conditional drug discrimination. In the CPP paradigm whether mice are feeling pain as tumours develop can be inferred by whether their preference for an environment where previously they were exposed to an analgesic (morphine) progressively increases. If mice are ?feeling? pain, in conditioned drug discrimination studies they should be able to be trained to use changes in this (due to analgesic treatment) as a cue to perform a task for a food reward. If the degree of pain is of little consequence, or if they do not have an internal state of ?what it is like to be in pain?, they would not show enhanced morphine seeking in the CPP paradigm, and would fail distinguish between the analgesic and saline in drug discrimination trials.
Correlating theses measures of subjective state with changes in behaviour, peripheral sensitisation and measures of tumour growth will give is a clearer picture of the pain caused by different types of tumour. This will allow us to refine endpoints in cancer studies. Of potentially even greater importance is that we will have established new methods for assessing the welfare consequences of other potentially painful procedures applied in laboratory rodents.