Paul Flecknell
Medical School, Comparative Biology Centre, Framlington Place, Newcastle, U.K.
It has been generally accepted for many years that if animals are to be used in biomedical research, then every effort should be made to minimise any pain or distress that they experience. This concept was formalized by Russell and Burch in 1959, as 'Refinement'. Considerable progress has been made over the last 10-15 years in one particular area, that of preventing or alleviating pain. It is quite clear, however, that very much more needs to be done if we are to deal with this problem effectively. This seminar will focus on one particular area, the management of post-surgical pain, but will also discuss other situations in which pain may be experienced.
We have now reached a stage at which it is generally accepted that animals experience pain following surgical procedures. Since we have access to a wide range of analgesics, it would seem a simple process to administer one of these agents to prevent or alleviate postoperative pain. Administering an analgesic is not sufficient as we need to:
Administer an appropriate analgesic.
Administer the analgesic at an appropriate dose.
Continue its administration at appropriate time intervals.
Stop administering the analgesic at an appropriate time after surgery.
Provision of effective pain relief requires that we address all of these points, and this can only be done by assessing the degree of pain experienced by the animal that is being treated. Animal pain assessment is difficult, time-consuming, and is rarely, if ever, implemented effectively. Many of those working with animals have made the assumption that they are able to assess pain, but studies that examine our ability to assess pain have shown that this is not the case. Although we may be able to assess the difference between pain-free animals and those experiencing severe pain, we are unable to grade pain accurately. These difficulties have led many research facilities to adopt a strategy in which all animals receive a fixed dose of a particular analgesic drug. This approach has the advantage of simplicity and if we assume that administration of at least some analgesic will always be beneficial, then it seems a reasonable and humane policy. It is, however, fundamentally flawed:
The analgesic dose rates selected are based on very limited data
The dose rates needed will vary greatly between different individuals, and between different ages, sexes and strains of animal.
The dose required will vary depending upon the type of surgical procedure, and the expertise of the surgeon.
In man, the use of fixed dose regimens has been identified as one of the factors contributing to inadequate pain management, and it seems we are in danger of repeating this error. A further problem is that in man, the analgesic dose rates used were at least based upon clinical trials incorporating validated methods of pain assessment. In animals, we have very limited data of this type, and the dose regimens used are often extrapolated from results of analgesiometry. The huge variation in dose rates that are effective in these tests has not been appreciated. In addition, the relationships between doses effective in analgesiometric tests and dose rates effective in managing clinical pain have not been properly appreciated. These problems cannot be fully resolved until effective methods of pain assessment are implemented, but pain management strategies that make best use of our existing information can be recommended:
If methods of pain assessment have been developed for the species used, then these should be adapted to the requirements of the particular model.
If methods of pain assessment are not available, consider devoting resources to developing some form of scoring system for the model.
If pain scoring is not possible, determine the analgesic protocol based on clinical experience with other surgical procedures in the species in question.
Use dose rates that have been established using studies that have employed pain scoring systems.
When data on pain scoring is not available, estimate doses from results of analgesiometric studies using tonic (longer lasting) nociceptive stimuli (eg late phase formalin test).
Consider using multimodal and pre-emptive analgesic strategies.
Attempt to evaluate the efficacy of the analgesic regimen, if only by clinical assessment.
Although we are making progress in the field of post-surgical pain management, there are other areas of animal use in which pain management is rarely considered. This includes studies involving acute inflammatory processes, gastro-intestinal disturbances and neoplasia. We continue to debate the issue of refinement, and many countries seek to evaluate research proposals using some form of cost-benefit assessment. If we cannot properly assess the costs, due to our poor ability to assess pain, then we cannot perform this type of analysis on a wide range of different studies.
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