Foxworthy's proposed experiment will inherently and necessarily cause pain in rats, as this is the focus of the research. The reviewer in this scenario has asked Foxworthy to consider reducing the number of animals to be used in this experiment, in accordance with the principle of reduction from the 3Rs (ref. 1). The reviewer noted that surgery is performed on only one hind leg of each animal, thus the other leg could be used as a control on the same animal. However, this viewpoint fails to consider the animal as a whole, as each rat in this study will experience and respond to pain from sciatic nerve constriction throughout its whole body to some degree. The contralateral leg is therefore not a suitable control because the limb is not separate from the whole animal and not immune to systemic pain. It would compromise both the welfare of each rat and the experiment's data, which would introduce new unwanted variables and interactions, if Foxworthy were to follow the reviewer's suggestion.
Amendments in adherence to the principle of reduction must be evaluated with the entire experiment in perspective, as rigid interpretation of this principle can demand that an IACUC compromise its other responsibilities. It is a clear mandate of biomedical research that investigators reduce the number of animals used in experiments, so researchers must clearly justify their sample sizes. But they must also maintain concern for the welfare of each individual animal in their experiments. For Foxworthy's proposal, the IACUC must consider what level of pain and distress is acceptable for each rat. The upper limit of distress for each rat must be defined and not exceeded, even if this requires compromising other principles, such as reduction. The Guide for the Care and Use of Laboratory Animals explicitly states that “reduction involves strategies for obtaining comparable levels of information from the use of fewer animals or for maximizing the information obtained from a given number of animals (without increasing pain or distress) so that in the long run fewer animals are needed to acquire the same scientific information”1.
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