Opioid self-administration in the assessment of post-operative pain in rats

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Rats have a vital role in research to investigate new drugs and treatments, but this often requires that they are made unconscious (anaesthetised) before undergoing surgery. A common surgical procedure is laparotomy; an incision whereby the skin and underlying muscles are cut so the organs inside the abdomen are exposed. Scientists have a duty to ensure that after the animals experience little or no pain after they recover from anaesthesia. Because the animals cannot tell us how they feel, however, it is difficult to gauge how painful this is. Scientific research has shown that there are some behaviours that are particularly important for determining how much pain laparotomy surgery causes in rats, because they increase as a result of surgery, but can be reduced if pain relieving drugs (analgesics) are provided (usually injected prior to surgery). This research has shown that different analgesics have different abilities to reduce pain, depending on how much drug the rats are given, and on whether the important (pain-related) behaviours disappear completely or only partially. One major problem, however, is that the researchers are still unsure whether the treatments they use are the most effective, because regardless of the analgesic given to the rats, some subtle behaviour changes usually remain. It is therefore unclear whether the continued presence of these abnormal activities means the rats are still experiencing pain, and so, how effective the analgesic that was given had been. One way to try to fully understand what the rats are experiencing is to give them the opportunity to tell us how they feel, but as they cannot communicate with us, this can only be done indirectly. If the rats are experiencing pain after surgery, then, if given the chance, they should choose to take (self-administer) analgesics to reduce it. The amount of analgesic they choose to self-administer could then be used as an estimate of how much pain was caused by surgery. An essential step in testing this theory, however, is to ensure that the rats know that obtaining the drugs will provide pain relief. Because of this, they will first be trained that poking their nose into a hole in a test chamber will painlessly trigger an injection of a strong pain killer (remifentanil). Once they know this, they should increase the number of times they nose-poke according to how much pain they are experiencing. A very useful aspect of this experiment is that it can also be used to test the pain-relieving properties of other analgesic drugs. The rats will be provided with one of the drugs that, according to the results of behavioural investigations, should be effective for relieving the pain caused by surgery. One such drug is called meloxicam, and another is carprofen. If either of these is given prior to surgery, and the dose given completely eliminates pain, then the rats should not choose to self-administer additional remifentanil when they recover from anaesthesia. Is this occurs, then it will be very good evidence that pain was the reason the rats needed remifentanil. Another way to confirm this is to show that the rats will also consume more remifentanil if the type of surgery causes more pain. The rats will undergo 4 different procedures that will cause different amounts of pain, but none will be highly painful. If the rats continue take more remifentanil even after they have been given meloxicam or carprofen then this will mean that the dose of meloxicam or carprofen was not sufficient, and more was needed. Testing how much remifentanil the rats need over several days following surgery will produce the best possible information on how much pain is caused, how long it lasts and what dose of analgesic is best to prevent it in future. This information would be useful to other researchers who need to conduct laparotomy and other types of surgery as part of their research, and so help to improve the welfare of all rats undergoing surgery in scientific research.