Does pre-operative affective state influence the severity and duration of post-op pain in rats?

Several million rats are used world-wide in biomedical research, with many of these animals undergoing surgery or other procedures likely to cause pain and distress. Pain in laboratory animals is a cause for both ethical and scientific concern, and reducing this source of animal suffering is likely to help address public opposition to the use of animals in research, as well as improving the quality of the science produced. So far, efforts to reduce pain in animals have focussed on providing pain-killing drugs and more comfortable bedding material following surgery. However, recent evidence from humans undergoing surgery shows that the emotional state of people prior to surgery can have a significant effect on the severity and duration of the pain they experience following surgery, with happier people showing fewer symptoms and faster recovery than those that are anxious or depressed. This observation suggests a new approach to tackling post-operative pain in animals: perhaps if we can improve the emotional state of animals prior to surgery we can reduce the amount of post-operative pain they experience. Our aim in this project is to test this possibility. The first stage of the project will involve creating groups of rats with different emotional states, either happy, neutral or anxious/depressed. We will create happy rats by making sure that their cage environments are stable and predictable, and by providing them with a range of items such as blocks of wood, chewable bedding materials and houses that make their otherwise barren cages more varied and interesting. Anxious and/or depressed rats will be created by housing rats in barren cages in which various aspects of the environment are unpredictable. A number of previous observations confirm that environmental manipulations such as these are capable of producing differences in emotional state: rats housed in the improved conditions are typically more willing to explore novel environments and objects and more willing to engage in pleasurable activities such drinking sweetened water. Happy animals are also more optimistic when making decisions about unpredictable events. We will use all of these techniques to assess the state of our rats prior to their undergoing a common surgical procedure involving an incision in the abdomen. We aim to treat all the rats with pain killing drugs following surgery to reduce any unnecessary suffering. Although these drugs are known to reduce symptoms of pain in rats, they do not eliminate them completely, allowing us to assess the effects of the rats' emotional states prior to surgery on post-surgical pain. Following surgery we will measure how much pain the happy, neutral and anxious/depressed rats are experiencing by recording behaviour patterns known to be associated with pain, such as flinching and back arching. On the basis of what is known in humans, we predict that the happy rats will also show reduced severity and duration of pain following abdominal surgery. In a final stage of the project we will explore whether antidepressant drugs can also function to reduce the severity and duration of post-operative pain if given prior to surgery. We expect that these drugs might produce an improvement in our anxious/depressed rats, however we do not know whether these drugs will produce an additional improvement in our already happy rats. The results obtained from our research will increase our understanding of how the way in which we keep animals affects their welfare, both before and after they undergo potentially painful procedures such as surgery. On the basis of our findings we hope to produce recommendations for simple ways in which the welfare of laboratory rats can be improved.

Post-operative pain in research animals is of great public concern, and represents an uncontrolled source of variation in experiments. Efforts to relieve pain have focused on post-operative refinements including analgesic administration and provision of additional bedding. However, in humans, it has been shown that pre-operative affective state is an important predictor of post-surgical outcomes, including the severity and duration of pain experienced. This raises the question of whether the pre-operative affective state of animals could be similarly important. The aim of this project is to assess how pre-operative affective state affects the pain experienced following abdominal surgery in laboratory rats. Three levels of affective state will be induced in two strains of rats via manipulations of their home cage environment: super enriched cages (positive), standard lab conditions (neutral) and unpredictable conditions (negative). Differences in affective state will be confirmed using established and novel behavioural techniques including: open field and elevated plus maze performance, sucrose consumption, peripheral hypersensitivity and measures of cognitive bias. Following state manipulation, rats will be subjected to laparotomy. Post-operative pain will be assessed using a validated behavioural pain scoring system. We hypothesise that rats in a more positive state prior to surgery will experience post-operative pain of reduced severity and duration. Finally, we will ask whether administration of an antidepressant drug prior to surgery can either mimic (in rats housed in standard or unpredictable cages), or enhance (in rats housed in super enriched cages), the benefits of an enriched home cage environment. We urgently need to know whether affective state influences pain perception in laboratory animals, since this would greatly influence the importance attached to measures such as environmental enrichment, and offers an additional new dimension to pain management.